Jejunal Metastasis Colliding With a Borderline Tumor in the Ovary: A Hitherto Unreported Eventuality.

PubMed

Piana, Simonetta; Giunta, Alessandro; Valli, Riccardo

2015-10-01

Metastatic adenocarcinomas to the ovary can show morphologically innocuous areas simulating primary benign lesions or borderline tumors. Ruling out a metastasis can be a difficult issue for pathologists, especially when facing with cystic tumors. Because of the important clinical implications of differentiating metastatic adenocarcinomas from primary ovarian tumors, the integration of clinical, pathological, and immunohistochemical features is warranted, primarily in case of mucinous adenocarcinomas. Vice versa, the synchronous presence of a metastasis and a primary in the same ovary is virtually excluded as a very unlikely eventuality. Here, we describe a case of metastatic adenocarcinoma from the jejunum colliding with a seromucinous borderline tumor in the same ovary, an unreported eventuality so far. © The Author(s) 2015.

Adenocarcinoma of urinary bladder: A report of two patients.

PubMed

Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

[Bladder rupture caused by spontaneous perforation of an infected urachal cyst].

PubMed

Maruschke, M; Kreutzer, H J; Seiter, H

2003-06-01

Anomalies of the fetal urachus are rare. Normally, the postnatal urachus presents as a fibrous band extending from the bladder to the umbilicus. Urachal cysts may occur in postnatal life. Spontaneous perforation of urachal cysts is a very rare condition, which clinically may not be distinguishable from other acute abdominal conditions. We report a case of a 63-year-old male with a history of recurrent urinary tract infections and a bladder rupture caused by a spontaneous perforation of an infected urachal cyst. The symptomatology showed abdominal rigidity and pain, a palpable mass in the lower abdomen, and hematuria. Laboratory findings showed leukocytosis and an increased CRP level. The bladder rupture was confirmed by cystography. Bacteriologic examination identified Proteus vulgaris, Corynebacterium species, and Klebsiella pneumoniae. Most of the published cases in the literature report about intraperitoneal perforation of infected urachal cysts. In the present case, we found a spontaneous perforation of an infected urachal cyst leading to an extraperitoneal bladder rupture with an extraperitoneal limitation of the infection. The definitive therapy was complete surgical excision including a cuff of the bladder, drainage, and systemic broad-spectrum and local application of antibiotics. The further course was uneventful.

Surgery of metastatic anal sac adenocarcinoma in five dogs.

PubMed

Hobson, Howard Phil; Brown, Marjorie Raquel; Rogers, Kenita S

2006-04-01

To identify survival and morbidity information after surgery for metastases from apocrine gland anal sac adenocarcinomas (AGACA). Retrospective study. Five dogs with AGACA. Medical records of dogs that had surgery for treatment of metastatic AGACA between 1993 and 2003 were reviewed. Criteria for inclusion required that dogs had lymphadenectomy, with or without further debulking, as part of their treatment for metastatic AGACA and that the tissue was histologically confirmed as consistent with the primary AGACA. Signalment, history, physical examination findings, clinicopathologic data, imaging findings, surgical complications, number of surgeries, survival times, and cause of death were recorded. All dogs had a complete blood count, serum biochemical profile, serum electrolytes, 3-projection thoracic radiographs, abdominal radiographs and/or abdominal ultrasonography, and histologic confirmation of metastatic AGACA invading the regional lymph nodes and caudal abdomen. No surgical complications occurred. Three dogs were euthanatized; median survival, 20.6 months. One dog was alive for 19 months postoperatively. One dog had 5 sequential surgical procedures: 1 iliac lymphadenectomy and 4 debulking procedures of metastatic neoplastic tissue around and dorsal to the iliac vessels extending into the pelvic cavity, and was alive 54 months after initial surgery. Dogs with anal sac adenocarcinoma metastases to the iliac lymph nodes can experience long-term survival after surgical excision of the metastatic lesion. Lymphadenectomy may afford long-term survival to patients with metastatic anal sac adenocarcinoma.

Olaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-05-18

Estrogen Receptor Negative; HER2/Neu Negative; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Metastatic Malignant Solid Neoplasm; Primary Peritoneal High Grade Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-05-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Surgical management of primary, metastatic and recurrent anal sac adenocarcinoma in the dog: 52 cases.

PubMed

Barnes, D C; Demetriou, J L

2017-05-01

To report the outcomes and complications of a cohort of dogs with primary and recurrent anal sac adenocarcinoma managed with surgery as the first-line treatment. To report the use of lymph node cytology for identification of metastatic disease. Retrospective review of case records of a single referral centre population of dogs diagnosed with anal sac adenocarcinoma. Fifty-two clinical cases were identified. Altered ultrasonographic appearance of lymph nodes was highly consistent with metastatic disease as assessed by cytology and histopathology. Seven of 58 (12%) perineal surgeries had reported minor complications and seven (12%) others required further surgical intervention. Minor controllable intraoperative bleeding was the only complication noted associated with lymph node extirpation in two of 39 (5%) metastectomy procedures. Six dogs (12%) suffered local recurrence and 22 (42%) developed subsequent or recurrent nodal metastatic disease. From the time of detection of disease recurrence, median additional survival associated with a second surgical intervention was 283 days. Coeliotomy for lymph node metastatectomy in dogs with adenocarcinoma of the anal sac has low morbidity and should be considered in patients presenting with evidence of regional metastatic disease both at initial presentation and with recurrent disease. © 2017 British Small Animal Veterinary Association.

Hypertrophic osteopathy secondary to metastatic ovarian adenocarcinoma in a mare.

PubMed

Browne, Nimet S; Scarratt, William K; Robertson, John

2016-12-01

A 10-year-old Andalusian mare was presented for evaluation of weight loss, increasing periods of recumbency, and swelling of the lower limbs. Radiographs revealed severe palisading to solid periosteal new bone formation in numerous locations. Necropsy revealed a metastatic malignant adenocarcinoma of ovarian origin with secondary hypertrophic osteopathy.

Laparoscopic management of urachal cyst associated with umbilical hernia.

PubMed

Gregory, G C; Vijay, R; Ligaj, M; Shiwani, M H

2011-02-01

The urachal cyst is a rare clinical entity of a urachal remnant. It is usually asymptomatic but can present with haematuria, tumour, urachal stone and infection. We present a case of a 63-year-old lady with a body mass index (BMI) of 49 who presented with a painful swelling in the umbilical region associated with an umbilical hernia. An ultrasound and computed tomography (CT) scan showed a suspected herniation of an umbilical remnant cyst through a paraumbilical defect. Laparoscopy confirmed the urachal cyst of 3 cm in size with a band connected with the cyst down to the urinary bladder associated with a 3-cm paraumbilical hernia. We removed the cyst and repaired the hernia laparoscopically uneventfully, after which her recovery was perfect. Radiological and laparoscopic pictures have not been reported in the English literature before. Although this condition is very rare, we suggest that it should be considered in the differential diagnosis of painful paraumbilical swelling. CT scanning and laparoscopy seems to be valuable, especially in obese patients.

Metastasis to the appendix from adenocarcinoma of the ascending colon: A case report.

PubMed

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-03-01

Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis.

Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine-needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations.

PubMed

Song, Dae Hyun; Lee, Boram; Shin, Yooju; Choi, In Ho; Ha, Sang Yun; Lee, Jae Jun; Hong, Min Eui; Choi, Yoon-La; Han, Joungho; Um, Sang-Won

2015-07-01

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutation in pulmonary adenocarcinoma is clinically important due to its association with resistance to EGFR inhibitors and poor prognosis. To our knowledge, there has not been a comparative study focusing on cytological nuclear features of pulmonary adenocarcinoma harboring KRAS mutation (KRAS-AD). Hence, we compared the cytomorphology of metastatic KRAS-AD and EGFR-positive adenocarcinoma (EGFR-AD) in aspiration specimens from lymph nodes. Forty lymph node aspiration specimens from forty KRAS-AD patients were collected at Samsung Medical Center (Seoul, Korea) from 2009 to 2013. As a control group, 40 EBUS-FNA lymph node specimens from 20 EGFR-AD patients were collected. EGFR-AD specimens were evaluated at Samsung Medical Center (Seoul, Korea) from 2012 to 2013. All 80 specimens were histologically confirmed to metastatic adenocarcinoma. Two pathologists performed a blinded review of all specimens. Compared with EGFR-AD, KRAS-AD exhibited more severe nuclear pleomorphism (P < 0.001), coarse chromatin (P = 0.001), cherry-red nucleoli (P < 0.001) and naked tumor cells (P = 0.002) with necrotic (P < 0.001) and neutrophilic (P = 0.008) background. Our study provides the first demonstration of cytomorphologic differentiation between metastatic KRAS-AD and metastatic EGFR-AD in lymph node aspiration specimens. © 2014 Wiley Periodicals, Inc.

Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

ClinicalTrials.gov

2013-06-03

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

A Study of ASN007 in Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-29

Cancer; Malignancy; Neoplasia; Neoplasm; Neoplasm Metastasis; Colon Cancer; Colonic Neoplasms; Colon Cancer Liver Metastasis; Metastatic Cancer; Metastatic Melanoma; Metastatic Colon Cancer; Metastatic Lung Cancer; Non Small Cell Lung Cancer Metastatic; Pancreatic Cancer; Pancreas Cancer; Pancreas Adenocarcinoma; Pancreas Neoplasm; Metastatic Nonsmall Cell Lung Cancer; Metastatic Pancreatic Cancer

Metastatic anal sac adenocarcinoma in a dog presenting for acute paralysis

PubMed Central

2004-01-01

Abstract A 4-year old, female spayed terrier was referred for hind end paresis that rapidly progressed to paralysis. Spinal radiographs revealed vertebral collapse and bony lysis. Myelography confirmed spinal cord compression and surgical exploration found an extradural soft tissue mass. Metastatic anal sac adenocarcinoma was diagnosed at postmortem examination. PMID:15368742

Metastatic anal sac adenocarcinoma in a dog presenting for acute paralysis.

PubMed

Brisson, Brigitte A; Whiteside, Douglas P; Holmberg, David L

2004-08-01

A 4-year old, female spayed terrier was referred for hind end paresis that rapidly progressed to paralysis. Spinal radiographs revealed vertebral collapse and bony lysis. Myelography confirmed spinal cord compression and surgical exploration found an extradural soft tissue mass. Metastatic anal sac adenocarcinoma was diagnosed at postmortem examination.

Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

ClinicalTrials.gov

2018-05-02

BRCA1 Gene Mutation; BRCA2 Gene Mutation; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

ClinicalTrials.gov

2015-05-15

Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

[Nonsurgical and surgical treatment of an urachal fistula in an alpaca cria. A case report].

PubMed

Kubus, K; Wöckel, A; Felton, C; Schwarzenberger, J; Sobiraj, A

2015-01-01

Urachal fistula is a neonatal condition. There are two reported forms: a congenital and an acquired form. We describe the case of a 6-hour-old female alpaca cria that was presented with a damp umbilicus and a meconium impaction. Conservative treatment of the urachal fistula with local and systemic medication was unsuccessful after 6 days; therefore, a resection of the umbilicus under general anaesthesia was performed. Reconvalescence was uneventful.

Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke – case report and literature review

PubMed Central

O’Connell, David; Kaliaperumal, Chandrasekaran; Wyse, Gerald; McCarthy, Julie; Ryan, Aisling

2011-01-01

The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature. PMID:22669998

The utility and limitation of thyroid transcription factor-1 protein in primary and metastatic pulmonary neoplasms.

PubMed

Chang, Yih-Leong; Lee, Yung-Chie; Liao, Wei-Yu; Wu, Chen-Tu

2004-05-01

Thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor expressed in the thyroid and lung. The clinical utility and limitation of TTF-1 in primary or metastatic carcinomas of the lung have not been previously studied in detail. We examined TTF-1 expression in 510 primary lung and 107 metastatic neoplasms. TTF-1 was detectable in 4/99 (4%) squamous cell carcinomas, 169/176 (96%) solitary adenocarcinomas, 34/34 (100%) multifocal adenocarcinomas, 1/1 (100%) signet ring cell carcinoma, 16/20 (80%) mucinous adenocarcinomas, 23/23 (100%) nonmucinous bronchioloalveolar carcinomas, 19/36 (53%) small cell carcinomas, and 39/44 (89%) sclerosing hemangioma. TTF-1 was absent in all eight carcinoids, three atypical carcinoids, 23 pleomorphic carcinomas, 25 lymphoepithelioma-like carcinomas, the sarcomatous component of one pseudomesotheliomatous carcinoma, and one mesothelioma. In four combined small cell carcinomas and 12 adenosquamous carcinomas, TTF-1 expression was only demonstrated in the adenocarcinoma component. There were 78 TTF-1 non-immunoreactive metastatic cases from 22 livers, 20 colorectums, 10 breasts, six nasopharynx, four larynx, four ovaries, three salivary glands, three esophagus, two adrenal glands, two kidneys, one bile duct, and one endometrium. TTF-1 was also detected in all 10 cervical lymph nodes, seven brain, and 6/7 (86%) bony tissues of 24 patients with metastatic carcinomas of unknown primary site, but it was absent in 125 patients with metastatic carcinomas other than lung origin in cervical lymph nodes, brain, and bony tissues. These results indicate the clinical usefulness and limitation in certain primary and metastatic lung neoplasms.

Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

ClinicalTrials.gov

2015-09-10

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Metastasis to the appendix from adenocarcinoma of the ascending colon

PubMed Central

Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

2017-01-01

Abstract Rationale: Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. Patient concerns and diagnoses: A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. Interventions and outcomes: This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. Lessons: An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis. PMID:28296772

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

ClinicalTrials.gov

2018-03-29

Colorectal Adenocarcinoma; Gastric Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer; Unresectable Pancreatic Carcinoma

Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

PubMed Central

Kothadia, Jiten P.; Arju, Rezina; Kaminski, Monica; Ankireddypalli, Arvind; Duddempudi, Sushil; Chow, Jonathan; Giashuddin, Shah

2015-01-01

Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures. PMID:25883818

Metastatic adenocarcinoma of mammary-like glands of the vulva successfully treated with surgery and hormonal therapy.

PubMed

Benito, Virginia; Arribas, Sara; Martínez, David; Medina, Norberto; Lubrano, Amina; Arencibia, Octavio

2013-01-01

Vulvar cancer is a rare malignancy; most tumors are squamous cell type while adenocarcinomas are rare. Primary adenocarcinomas of the vulva predominantly include extramammary Paget's disease and sweat gland carcinomas. Greene first described a rare form of adenocarcinoma in 1936, which was called adenocarcinoma of mammary-like glands of the vulva because of its morphologic and immunohistochemical resemblance to breast adenocarcinomas. In the management of this entity, varying combinations of surgery, radiation therapy, systemic chemotherapy and/or hormonal therapy may be used, as in patients with orthotopic breast carcinoma. However, hormonal therapy leads the way in patients with positive hormonal receptors, where other therapies cannot be used due to comorbidities or advanced age. We present the first reported case of an elderly patient with metastatic vulvar adenocarcinoma arising from mammary-like glands, successfully treated with a combination of surgery and hormonal therapy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Biometric assessment of prostate cancer's metastatic potential.

PubMed

Cooper, C R; Emmett, N; Harris-Hooker, S; Patterson, R; Cooke, D B

1994-01-01

Currently, no protocol exists that can assess the metastatic potential of prostate adenocarcinoma. The reason for this is partly due to the lack of information on cellular changes that result in a tumor cell's becoming metastatic. In this investigation, attempts were made to devise a method that correlated with the metastatic potential of AT-1, Mat-Lu, and Mat-LyLu cell lines of the Dunning R-3327 rat prostatic adenocarcinoma system. To accomplish this, we applied BioQuant biometric parameters, i.e., area, shape factor, and cell motility. AT-1 had a lower shape factor and a greater area as compared with the more highly metastatic Mat-Lu subline. No significant difference in area or shape factor was detected between the AT-1 cell line and the highly metastatic Mat-LyLu line. However, the lowly metastatic AT-1 line had less motility as compared with the Mat-Lu and Mat-LyLu lines. This study revealed that metastatic potential could be partially predicted via area and shape factor and accurately predicted via cell motility.

The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells.

PubMed

Okusha, Yuka; Eguchi, Takanori; Sogawa, Chiharu; Okui, Tatsuo; Nakano, Keisuke; Okamoto, Kuniaki; Kozaki, Ken-Ichi

2018-05-15

Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. © 2018 Wiley Periodicals, Inc.

Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer

ClinicalTrials.gov

2018-03-27

Biliary System Disorder; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Gastroesophageal Junction Adenocarcinoma; Homologous Recombination Deficiency; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Stage IV Colorectal Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma

ClinicalTrials.gov

2015-06-03

Extrahepatic Bile Duct Adenocarcinoma; Gallbladder Adenocarcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Hilar Cholangiocarcinoma; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Undifferentiated Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma

Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer

ClinicalTrials.gov

2018-05-29

Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

ClinicalTrials.gov

2018-02-22

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

ClinicalTrials.gov

2016-02-18

Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

PubMed

Garg, Shivani; Mulki, Ramzi; Sher, Daniel

2016-03-08

Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

Metastatic pancreatic adenocarcinoma and renal cell carcinoma treated with gemcitabine and sunitinib malate. A case report.

PubMed

Bharthuar, Anubha; Pearce, Lori; Litwin, Alan; LeVea, Charles; Kuvshinoff, Boris; Iyer, Renuka

2009-09-04

Pancreatic adenocarcinoma and renal cell carcinoma are relatively frequent cancers that have been rarely reported as synchronous primary malignancies. When present simultaneously, they pose a therapeutic challenge given the many available targeted agents with reported efficacy in renal cell cancer and limited options for metastatic pancreatic cancer. We report the case of a 43-year-old Caucasian gentleman diagnosed simultaneously with metastatic pancreatic adenocarcinoma and localized renal cell carcinoma treated with combination chemotherapy, consisting of gemcitabine and sunitinib. Patient had a radiographic response and prolonged progression free survival of twenty six weeks; side effects were manageable and included grade 3 neutropenia and grade 2 hypertension. This encouraging response, safety profile and progression free survival response suggest that we should further examine this and other such regimens to improve clinical outcomes for maximum efficacy with minimal side-effects.

Next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas Demonstrates Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas.

PubMed

Crumley, Suzanne M; Pepper, Kristi L; Phan, Alexandria T; Olsen, Randall J; Schwartz, Mary R; Portier, Bryce P

2016-06-01

-Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations. -To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma. -Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations. -Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4. -The somatic mutations identified in our rectal adenocarcinoma cohort showed a strong correlation to those previously characterized in colonic adenocarcinoma. In addition, most rectal adenocarcinomas harbored identical somatic mutations in both the primary tumor and metastasis. These findings demonstrate evidence that rectal adenocarcinoma follows a similar molecular pathogenesis as colonic adenocarcinoma and that sampling either the primary or metastatic lesion is valid for initial evaluation of somatic mutations and selection of possible targeted therapy.

Metastatic prostate adenocarcinoma to the penis: a series of 29 cases with predilection for ductal adenocarcinoma.

PubMed

Ellis, Carla L; Epstein, Jonathan I

2015-01-01

Twenty-nine men with metastatic prostate adenocarcinoma to the penis were identified at our institution between 1993 and 2013. Of the 29 patients, 19 had a prior history of adenocarcinoma of the prostate, and 8 of those had ductal features in the primary lesion. Sixteen of 29 revealed ductal features in the metastasis. Seven of the 8 cases with ductal features in the primary had ductal features in the penile metastasis. Seven penile metastases were proven to be of prostatic origin solely by immunohistochemistry. Three cases were originally misdiagnosed as urothelial carcinoma upon review of the penile lesion. Other variant morphologies in the metastases included sarcomatoid carcinoma, small cell carcinoma, and adenosquamous carcinoma. In summary, prostate carcinoma involving the penis displays ductal features considerably more often than prostate cancer in general. Features that can cause difficulty in recognizing metastatic prostate adenocarcinoma to the penis include the unusual anatomic site for prostate cancer, poor differentiation, an increased prevalence of variant morphology, a long interval from the primary lesion, and, in some cases, no documented history of a primary prostatic lesion. Immunohistochemical analysis should be performed to rule out prostate carcinoma in penile/penile urethral tumors with morphology that differs from typical squamous or urothelial carcinoma. Even in the setting of metastatic disease, there is a critical need for an accurate diagnosis so that the appropriate therapy can be initiated, symptomatic relief can be provided, and long-term survival achieved in some cases, while at the same time avoiding penectomy for a misdiagnosis of a primary penile cancer.

Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

ClinicalTrials.gov

2018-01-08

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

ClinicalTrials.gov

2017-06-13

Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Advanced Adult Primary Liver Cancer; Gastrointestinal Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

ClinicalTrials.gov

2018-03-22

Adenocarcinoma Metastatic; Biliary Tract Cancer; Adenocarcinoma of the Biliary Tract; Adenocarinoma Locally Advanced; Non-Resectable Hepatocellular Carcinoma; Intrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Carcinoma

Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer

ClinicalTrials.gov

2017-09-19

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Unresectable Esophageal Carcinoma

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2017-07-15

Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

Prostate carcinoma metastatic to the skin as an extrammamary Paget’s disease

PubMed Central

2012-01-01

Aim The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified. Discussion and conclusions We review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276 PMID:22901743

A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk

DTIC Science & Technology

2007-11-01

1 mucinous adenocarcinomas 3 clear-cell carcinomas 1 malignant mixed mesodermal tumor 3 metastatic ovarian carcinomas 5 undifferentiated carcinomas 2...serous LMP tumors 2 mucinous LMP tumors 1 benign serous cystadenoma Ovarian tumor blocks 38 18 serous adenocarcinomas 5 mucinous adenocarcinomas 2...endometrioid adenocarcinomas 3 clear cell carcinomas 6 serous LMP 3 mucinous LMP 1 benign fibrous cystadenoma MMPs IN EARLY OVARIAN CANCER DEVELOPMENT

Presentation of renal cell carcinoma as cervical polyp metastasis.

PubMed

Godfrey, Gwendolyn J; Moore, Grace; Alatassi, Houda

2010-10-01

Secondary cervical adenocarcinomas are most commonly seen owing to the extension of a primary endometrial adenocarcinoma. Metastatic tumors from other sites are rather uncommon and, when seen, are most frequently from the ovaries, gastrointestinal tract, or breast. We report a case of metastatic renal cell carcinoma, clear cell variant, to the cervix, which presented as a cervical polyp in a postmenopausal female. To our knowledge, this is the fourth reported case of renal cell carcinoma metastatic to the cervix. This case is only the third in which the cervical metastasis was the presenting sign of renal cell carcinoma and the first in which the clinical presentation was as a cervical polyp.

Urachal Cyst Causing Small Bowel Obstruction in an Adult with a Virgin Abdomen.

PubMed

O'Leary, Michael P; Ashman, Zane W; Plurad, David S; Kim, Dennis Y

2016-01-01

Introduction . A patent urachus is a rare congenital or acquired pathology, which can lead to complications later in life. We describe a case of urachal cystitis as the etiology of small bowel obstruction in an adult without prior intra-abdominal surgery. Case Report . A 64-year-old male presented to the acute care surgery team with a 5-day history of right lower quadrant abdominal pain, distention, nausea, and vomiting. He had a two-month history of urinary retention and his past medical history was significant for benign prostate hyperplasia. On exam, he had evidence of small bowel obstruction. Computed tomography revealed high-grade small bowel obstruction secondary to presumed ruptured appendicitis. In the operating room, an infected urachal cyst was identified with adhesions to the proximal ileum. After lysis of adhesions and resection of the cyst, the patient was subsequently discharged without further issues. Conclusion . Although rare, urachal pathology should be considered in the differential diagnosis when evaluating a patient with small bowel obstruction without prior intraabdominal surgery, hernia, or malignancy.

Solitary Metastasis to the Facial/Vestibulocochlear Nerve Complex: Case Report and Review of the Literature.

PubMed

Ariai, M Shafie; Eggers, Scott D; Giannini, Caterina; Driscoll, Colin L W; Link, Michael J

2015-10-01

Distant metastasis of mucinous adenocarcinoma from the gastrointestinal tract, ovaries, pancreas, lungs, breast, or urogenital system is a well-described entity. Mucinous adenocarcinomas from different primary sites are histologically identical with gland cells producing a copious amount of mucin. This report describes a very rare solitary metastasis of a mucinous adenocarcinoma of unknown origin to the facial/vestibulocochlear nerve complex in the cerebellopontine angle. A 71-year-old woman presented with several month history of progressive neurological decline and a negative extensive workup performed elsewhere. She presented to our institution with complete left facial weakness, left-sided deafness, gait unsteadiness, headache and anorexia. A repeat magnetic resonance imaging scan of the head revealed a cystic, enhancing abnormality involving the left cerebellopontine angle and internal auditory canal. A left retrosigmoid craniotomy was performed and the lesion was completely resected. The final pathology was a mucinous adenocarcinoma of indeterminate origin. Postoperatively, the patient continued with her preoperative deficits and subsequently died of her systemic disease 6 weeks after discharge. The facial/vestibulocochlear nerve complex is an unusual location for metastatic disease in the central nervous system. Clinicians should consider metastatic tumor as the possible etiology of an unusual appearing mass in this location causing profound neurological deficits. The prognosis after metastatic mucinous adenocarcinoma to the cranial nerves in the cerebellopontine angle may be poor. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment, Outcomes, and Clinical Trial Participation in Elderly Patients With Metastatic Pancreas Adenocarcinoma

PubMed Central

Li, Daneng; Capanu, Marinela; Yu, Kenneth H.; Lowery, Maeve A.; Kelsen, David P.; O’Reilly, Eileen M.

2016-01-01

Studies on the treatment patterns and outcomes of elderly patients with metastatic pancreas cancer remain limited. Therefore, an analysis of systemic therapy use, clinical trial participation, and outcomes in elderly patients with metastatic pancreas cancer was performed at our institution. Elderly patients who received systemic therapy had a longer survival compared with those who did not. However, therapeutic clinical trial participation was low and should be encouraged Background Pancreas adenocarcinoma has a median age at diagnosis of 71 years. Limited studies have focused on the treatment of elderly patients with pancreas cancer. Patients and Methods An analysis of systemic therapy use, clinical trial participation, and overall outcomes of 237 patients with metastatic pancreas adenocarcinoma ≥ 75 years of age evaluated at Memorial Sloan-Kettering Cancer Center between 2005 and 2013 was undertaken. Results Median overall survival was 7 months for the entire study population. A total of 197 (83%) patients received systemic therapy, which was significantly associated with longer overall survival (P < .01). No significant difference was detected in survival between age groups 75 to 79, 80 to 84, and ≥ 85 years of age among those who received systemic therapy (P = .49). Seventy-seven (32%) patients participated in a clinical trial of whom 13 (5%) patients were enrolled in a therapeutic trial, including no patients aged ≥ 85 years. Multivariate analysis demonstrated that presence of liver metastases (P < .001), performance status (P < .001), and number of systemic agents (P < .001) were significantly associated with survival. Conclusion Receipt of systemic therapy was associated with longer survival in elderly patients ≥ 75 years of age with metastatic pancreas adenocarcinoma. Therapeutic clinical trial participation among these patients was low and future development of prognostic models for appropriate patient selection is warranted. PMID:26072442

A Comparative Review of Demographics, Incidence, and Epidemiology of Histologically Confirmed Intracranial Tumors in Brazil and Bulgaria

PubMed Central

Sarraf, Jonathan S; Matev, Boyko K; Dzhenkov, Deyan L; Kitanova, Martina; Iliev, Bogomil; Ghenev, Peter; Tonchev, Anton B; Enchev, Yavor; Adami, Fernando; De Carvalho, Luis Eduardo W

2018-01-01

Intracranial tumors (ICTs) attract numerous scientific teams and tremendous financial resources worldwide. These lesions of the central nervous system (CNS) can be both benign and malignant in biological behavior as well as local or metastatic in origin. We compared data from two studies on primary and metastatic ICTs from Brazil and Bulgaria, based on histopathologically confirmed ICTs from tertiary health centers. Primary ICTs significantly outweigh the frequency of metastatic ICTs. Primary ICTs represent 86.45% in Brazil and 69.17% in Bulgaria, with around 60% of their totals being malignant. There is a statistical dominance of tumors from the neuroepithelial origin, with the most common entry being glioblastoma multiforme. The second-most common primary ICT group comprises tumors of meningeal origin. Metastatic ICTs show great variance; 13.55% in Brazil and 31.38% in Bulgaria of all ICT cases being attributed to them. However, metastatic ICTs are even a more diverse group than neuroepithelial tumors, with the majority of this group comprising metastatic colorectal adenocarcinoma (almost exclusively in males), metastatic breast adenocarcinoma in females, metastatic pulmonary carcinomas (primarily from the non-small cell group with a male predominance), and metastatic melanoma with an even gender ratio. PMID:29682433

Primary yolk sac tumor of the urachus.

PubMed

Romero-Rojas, Alfredo Ernesto; Messa-Botero, Oscar Alberto; Melo-Uribe, Mario Alexander; Díaz-Pérez, Julio Alexander; Chinchilla-Olaya, Sandra Isabel

2011-10-01

Neoplasms originating from the urachus are rare. The most common urachal malignancy is adenocarcinoma, whereas extragonadal germ cell tumors, primarily of the urachus, are an extremely rare finding. To describe a primary yolk sac tumor (YST) of the urachus in an adult. A 44-year-old woman presented with 6 months of pelvic pain associated with a sensation of progressive mass growth. At the time of tumor resection, the tumor was found to be attached by a pedicle to the dome of the bladder, with no injury to the adjacent organs. Pathological study showed a neoplasm with epithelioid cells, pseudocysts, a myxomatous background, and Schiller-Duval body formations. Immunohistochemistry stains showed positivity to AE1/AE3, α-1-fetoprotein, and α-1-antitrypsin and negativity to other markers. An unusual case of a YST in the urachus is presented. This is the first reported adult case based on the authors' bibliographic search.

Bronchogenic adenocarcinoma metastatic tumor mimicking a dentoalveolar abscess in the maxilla.

PubMed

Salarić, Ivan; Miloš, Mate; Brajdić, Davor; Manojlović, Spomenka; Trutin Ostović, Karmen; Macan, Darko

2016-01-01

Intraosseous metastatic tumors (IOM) in maxilla are less frequent than the soft tissue metastatic tumors. Lung and bronchogenic metastatic tumors are uncommon in the maxilla. We present a maxillary bronchogenic metastasis with a rare clinical appearance. IOM was misdiagnosed as a dentoalveolar abscess and treated with antibiotics for 3 weeks. After not responding to antibiotics, the patient's general dental practitioner forwarded the patient to the Department of Oral and Maxillofacial Surgery. The associated tooth was extracted and the patient was recalled 1 week later. No signs of improvement were observed, and cytology, biopsy, and radiology diagnostics were performed. Cytologic results and biopsy could not differentiate a metastatic tumor from a salivary duct carcinoma. Ultimately, negative androgen receptors immunohistochemistry supported the diagnosis of bronchogenic metastatic adenocarcinoma. This case report stresses the importance of taking a thorough medical history. To our knowledge, this is the third bronchogenic IOM to the maxilla reported, mimicking a dentoalveolar abscess. General dental practitioners are among the first in contact with oral metastatic tumors and it is therefore important to report unusual clinical cases, as they present a diagnostic challenge for both the clinician and the pathologist.

TNFRSF10C copy number variation is associated with metastatic colorectal cancer

PubMed Central

Tanenbaum, Daniel G.; Hall, William A.; Colbert, Lauren E.; Bastien, Amanda J.; Brat, Daniel J.; Kong, Jun; Kim, Sungjin; Dwivedi, Bhakti; Kowalski, Jeanne; Landry, Jerome C.

2016-01-01

Background Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). Methods Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. Results TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13–10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42–42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). Conclusions TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma. PMID:27284460

CPI-613 and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-26

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

PubMed Central

Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

2010-01-01

Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

Adenocarcinoma of the rete testis - a rare case of testicular malignancy.

PubMed

Chovanec, M; Mego, M; Sycova-Mila, Z; Obertova, J; Rajec, J; Palacka, P; Mardiak, J

2014-01-01

Adenocarcinoma of rete testis is an extremely rare dia-gnosis described in around 70 patients worldwide. The prognosis of the disease in metastatic stage is very poor and there is no standard systemic treatment available. Herein we present a unique case report of a 47-year- old man with metastatic adenocarcinoma of rete testis who achieved substantial disease response after four cycles of paclitaxel, ifosfamide and cisplatin. The chemotherapy was administered in five -day regimen, which comprised 250 mg/ m2 of paclitaxel on day one, 20 mg/ m2 of cisplatin on day one to five and 1,2 g/ m2 of ifosfamide on day one to five, in a three-week interval. The patient received prophylactic pegfilgrastim after each cycle of TIP. The treatment was well tolerated -  without any significant toxicity. Patient achieved a partial 14- month remission. On basis of this experience we suggest that paclitaxel, ifosfamide and cisplatin might be adopted as novel agents in treatment of rete testis adenocarcinoma.

Concordant and Discordant EGFR Mutations in Patients with Multifocal Adenocarcinomas: Implications for EGFR Targeted Therapy

PubMed Central

Chuang, Jody C.; Shrager, Joseph B.; Wakelee, Heather A.; Neal, Joel W.

2016-01-01

Purpose Adenocarcinoma remains the most common subtype of lung cancer in the United States. Most patients present with tumors that are invasive and often metastatic, but some patients develop multiple precursor in-situ or minimally invasive adenocarcinoma tumors which can be synchronous and metachronous. These precursor lesions harbor the same spectrum of genetic mutations found in pure-invasive adenocarcinomas, such as EGFR, KRAS and p53 mutations. It is less clear, however, if separate lesions in patients who present with multifocal disease share common underlying genetic driver mutations. Methods Here we review the relevant literature on molecular driver alterations in adenocarcinoma precursor lesions. We then report four cases with multifocal EGFR mutant adenocarcinomas in whom we performed molecular testing on 2 separate lesions. Findings In two of these patients, the mutations are concordant, and in two cases the mutations are discordant. A review of the literature demonstrates increasing evidence that lesions with discordant mutations may confer a more favorable prognosis, since they are unlikely to represent metastases. Implications Our findings suggest that the emergence of the dominant EGFR driver alteration is often independent between lesions in patients with multifocal adenocarcinomas, and thus the same targeted therapy may not be effective for all lesions. However, genetic testing of multiple lesions can help distinguish separate primary tumors from metastatic disease. PMID:27368115

Intrathyroid metastasis presenting as a solitary thyroid nodule: an unusual case of clinically silent lung cancer.

PubMed

Sharma, U K; Rauniyar, R K; Adhikary, S; Sinha, A

2008-01-01

Metastases in the thyroid gland are very rare. Carcinoma lung is one of the tumours, which may metastasize to the thyroid. We report a 60-year-old lady with intrathyroid metastasis presenting as a solitary thyroid nodule. Fine needle aspiration cytology from the nodule showed features of metastatic adenocarcinoma. Further detail evaluation revealed primary lung adenocarcinoma with secondaries to adrenals, retroperitoneal and bilateral axillary nodes. This report emphasizes this unusual clinical presentation of carcinoma lung with wide spread secondaries; and a solitary thyroid nodule can be a presenting complain of a metastatic disease.

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis.

PubMed

Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mannhart, Meinrad; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Decker, Michael; Abdel-Rahman, Omar

2017-03-14

To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival. Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

[A Case of Uterine Body Metastasis from Sigmoid Colon Adenocarcinoma].

PubMed

Mayumi, Katsuyuki; Terakura, Masanobu; Hori, Takaaki; Takemura, Masashi

2017-11-01

We report a case of metastatic carcinoma to the uterine body from a colorectal adenocarcinoma. A 73-year-old woman underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma 2 years before. In the following study, her serum carcinoembryonic antigen level was elevated, and a uterine body tumor invading the rectal wall was detected via enhanced computed tomography. Colonoscopic examination revealed an elevated lesion at the rectum, which was diagnosed as an adenocarcinoma. Based on these results, we diagnosed the uterine tumor as metastatic tumor from the colon carcinoma. Immunostaining was negative for CK7, but positive for CK20. Thus, we confirmed metastasis of the sigmoid colon cancer to the uterus. Metastasis to the female genital tract from extragenital malignancies are rare, and the prognosis is extremely poor. However, some patients attain long-term survival by surgical intervention even in such cases.

Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Keohane, Catherine; Bermingham, Niamh; Kaar, George

2011-01-01

The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient’s age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with ‘red flag’ symptoms. PMID:22674960

Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation.

PubMed

Erdogan, Bulent; Kodaz, Hilmi; Karabulut, Senem; Cinkaya, Ahmet; Tozkir, Hilmi; Tanriverdi, Ozgur; Cabuk, Devrim; Hacioglu, Muhammed Bekir; Turkmen, Esma; Hacibekiroglu, Ilhan; Uzunoglu, Sernaz; Cicin, Irfan

2016-11-10

Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.

Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial.

PubMed

Reni, Michele; Cereda, Stefano; Milella, Michele; Novarino, Anna; Passardi, Alessandro; Mambrini, Andrea; Di Lucca, Giuseppe; Aprile, Giuseppe; Belli, Carmen; Danova, Marco; Bergamo, Francesca; Franceschi, Enrico; Fugazza, Clara; Ceraulo, Domenica; Villa, Eugenio

2013-11-01

New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P<0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

PubMed

Scott, Lesley J

2018-05-01

Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature.

PubMed

Zheng, Yulong; Fang, Weijia; Xu, Nong

2012-12-01

Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib dose-reduction was initiated. HFS may occur with icotinib, especially when administered in high doses.

Metastatic endocervical adenocarcinoma in a western lowland gorilla (Gorilla g. gorilla): no evidence of virus-induced carcinogenesis.

PubMed

Olias, P; Schulz, E; Ehlers, B; Ochs, A; Mundhenk, L; Klopfleisch, R

2012-04-01

Cervical Cancer is the second most common cancer among women. Nevertheless, similar tumours have only been rarely described in Great Apes. This report characterizes the pathological and molecular features of a metastatic endocervical adenocarcinoma in a Western lowland gorilla (Gorilla g. gorilla). Necropsy and histopathology was performed to identify the cause of the disease in an cachectic 50-year-old western lowland gorilla. Immunohistochemistry for Ki67, oestrogen receptor alpha and ERBB2 was performed to characterize the tumor. In addition, Pan-herpesvirus and Pan-papillomavirus PCR were used to identify a possible viral cause. The endoccervical carcinoma showed a severe metastatic spread to the lung, brain and bone and was herpesvirus and papillomavirus-negative. Most tumor cells were ERBB2-positive, 15% of tumor cells were Ki67-positive and only few tumor cells had oestrogen receptor alpha expression. Histopathologically and immunohistochemically, the tumour had striking similarities to human endocervicial adenocarcinomas of the common type. However, PCR analysis failed to identify herpes- or papillomaviral DNA in the tumor at the time of necropsy, thus leaving the question for cause of the disease open. © 2012 John Wiley & Sons A/S.

First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma.

PubMed

Chakrabarti, Sakti; Dong, Haidong; Paripati, Harshita R; Ross, Helen J; Yoon, Harry H

2018-04-19

Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease. © AlphaMed Press 2018.

Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

PubMed

Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

2015-05-01

Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.

Modeling Efficacy of Bevacizumab Treatment for Metastatic Colon Cancer

PubMed Central

Islam, Rezwan; Chyou, Po-Huang; Burmester, James K

2013-01-01

Purpose: Bevacizumab, an FDA-approved adjuvant treatment for metastatic colon cancer, has extended survival for many patients. However, factors predicting response to treatment remain undefined. Patients and Methods: Relevant clinical and environmental data were abstracted from medical records of 149 evaluable patients treated with bevacizumab for metastatic colon cancer at a multi-specialty clinic. Tumor response was calculated from radiologic reports using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and verified by oncologist review. Patients with at least one occurrence of complete or partial response or stable disease were classified as responders; those exhibiting progressive disease were classified as non-responders. Results: Univariate analysis demonstrated that blood in stool (P<0.05), unexplained weight loss (P<0.05), primary colon cancer site (P<0.05), chemotherapy treatment of primary tumor site (P<0.05), and adenocarcinoma versus adenoma subtype (P<0.05) was associated with tumor responsiveness. Factors remaining statistically significant following multivariate modeling included adenocarcinoma as tumor cell type versus other adenocarcinoma subtypes (OR=6.35, 95% CI: 1.08-37.18), chemotherapy treatment applied to primary tumor (OR= 0.07, 95% CI: 0.0-0.76,), tumor localization to cecal/ascending colon (OR=0.061, 95% CI: 0.006-0.588,), and unexplained weight loss (OR=0.1, 95% CI: 0.02-0.56,). Chemotherapy treatment of primary tumor, unexplained weight loss, and cecal/ascending localization of the tumor were associated with poorer outcomes. Adenocarcinoma as cell type compared to other adenocarcinoma subtypes was associated with better response to bevacizumab treatment. Conclusion: Results suggest that response to bevacizumab therapy may be predicted by modeling clinical factors including symptomology on presentation, tumor location and type, and initial response to chemotherapy. PMID:23678369

Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma.

PubMed

Aprikian, A G; Cordon-Cardo, C; Fair, W R; Reuter, V E

1993-06-15

This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma. Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies. NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases. This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.

Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer

ClinicalTrials.gov

2018-03-22

Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Metastatic Malignant Solid Neoplasm; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Unresectable Solid Neoplasm

[Rare umbilical anomalies].

PubMed

Kysucan, J; Malý, T; Neoral, C

2010-12-01

Umbilicus is a scar, which is the place of the previous merger of the fetus with the umbilical cord. After birth, it has no known function, however, unless the umbilical annulus is completely closed, umbilical hernia may occur. Umbilical scar is also an area where may occur a number of anomalies that may be present alone or together with umbilical hernia. Failure of involution leads to persistence of omphalomesenteric duct and urachal remnants. These embryonic remnants may cause more or less significant clinical problems, or may be completely asymptomatic and may be diagnosed at random. The authors present their own group of patients who were diagnosed and dealt with the defect omphalomesenteric duct or urachus. In past 7 years we observed 35 children with these abnormalities. A large group of patients represents incidental findings during elective surgery for umbilical hernia. Another large group are patients with symptomatic or asymptomatic Meckel's diverticulum. The anatomical observations, clinical manifestations, complications and treatment of these anomalies are mentioned. A total of 35 children were found with these birth defects. In 23 cases we observed omphalomesenteric duct disorders and 12 urachal remnants were reported. Of these, 12 abnormalities were found incidentally during elative procedure for umbilical hernia. Asymptomatic or symptomatic Meckel's diverticulum appeared in 16 cases. Surgical treatment included resection or exstirpation, if urachal anomaly was accompanied then partial resection of the bladder vertex was added. Postoperative complications emerged in 4 cases, three times it was ileus from adhesions 6 months after surgery, once postoperative cystitis appeared and was treated conservatively. Birth abnormalities of the umbilicus are relatively rare diseases that may occur in the pediatric population. Omfalomesenteric duct and urachal anomalies constitute a major group of these congenital disorders and are often associated with umbilical hernia. They can be diagnosed soon after birth or later in life. Surgical treatment involves excision or radical exstirpation to prevent early or late complications (urachal carcinoma in adulthood).

Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology

NASA Astrophysics Data System (ADS)

Qiu, Tian; Guo, Huiqin; Zhao, Huan; Wang, Luhua; Zhang, Zhihui

2015-06-01

Identification of multi-gene variations has led to the development of new targeted therapies in lung adenocarcinoma patients, and identification of an appropriate patient population with a reliable screening method is the key to the overall success of tumor targeted therapies. In this study, we used the Ion Torrent next-generation sequencing (NGS) technique to screen for mutations in 89 cases of lung adenocarcinoma metastatic lymph node specimens obtained by fine-needle aspiration cytology (FNAC). Of the 89 specimens, 30 (34%) were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations. Seven (8%) samples harbored KRAS mutations, and three (3%) samples had BRAF mutations involving exon 11 (G469A) and exon 15 (V600E). Eight (9%) samples harbored PIK3CA mutations. One (1%) sample had a HRAS G12C mutation. Thirty-two (36%) samples (36%) harbored TP53 mutations. Other genes including APC, ATM, MET, PTPN11, GNAS, HRAS, RB1, SMAD4 and STK11 were found each in one case. Our study has demonstrated that NGS using the Ion Torrent technology is a useful tool for gene mutation screening in lung adenocarcinoma metastatic lymph node specimens obtained by FNAC, and may promote the development of new targeted therapies in lung adenocarcinoma patients.

Prognostic value of E-cadherin, beta-catenin, CD44v6, and HER2/neu in metastatic cutaneous adenocarcinoma.

PubMed

Pozdnyakova, Olga; Hoang, Mai M P; Dresser, Karen A; Mahalingam, Meera

2009-08-01

Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases. To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade. E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%). Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin--a member of the cadherin family functioning as an invasion suppressor molecule. These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.

VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

ClinicalTrials.gov

2017-12-26

Colon Carcinoma Metastatic in the Liver; Colorectal Adenocarcinoma; Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

ClinicalTrials.gov

2018-03-22

Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer.

PubMed

Takeshita, Nobuyoshi; Fukunaga, Toru; Kimura, Masayuki; Sugamoto, Yuji; Tasaki, Kentaro; Hoshino, Isamu; Ota, Takumi; Maruyama, Tetsuro; Tamachi, Tomohide; Hosokawa, Takashi; Asai, Yo; Matsubara, Hisahiro

2015-11-28

A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to continue capecitabine administration with extension of interval period and dose reduction. After 2 years and 2 mo from starting capecitabine plus bevacizumab regimen, Virchow lymph nodes had slowly grown up to 17 mm. Because no recurrence had been detected besides Virchow lymph nodes for this follow up period, considering the side effects and quality of life, surgical resection was selected. We performed left supraclavicular lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer. After the fourth operation, the patient selected follow up without chemotherapy. Now we follow up her without recurrence and keep her quality of life high.

Inhibition of the biosynthesis of prostaglandin E2 by low dose aspirin: implications for adenocarcinoma metastasis

PubMed Central

Boutaud, Olivier; Sosa, I. Romina; Amin, Taneem; Oram, Denise; Adler, David; Hwang, Hyun S.; Crews, Brenda C.; Milne, Ginger; Harris, Bradford K.; Hoeksema, Megan; Knollmann, Bjorn C.; Lammers, Philip E.; Marnett, Lawrence J.; Massion, Pierre P.; Oates, John A.

2016-01-01

Meta-analyses have demonstrated that low dose aspirin reduces the risk of developing adenocarcinoma metastasis, and when colon cancer is detected during aspirin treatment, there is a remarkable 83% reduction in risk of metastasis. As platelets participate in the metastatic process, the anti-platelet action of low dose aspirin likely contributes to its anti-metastatic effect. Cycloxooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) also contributes to metastasis, and we addressed the hypothesis that low dose aspirin also inhibits PGE2 biosynthesis. We show that low dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers (p <0.0001). Aspirin is found to be more potent in colon adenocarcinoma cells than in the platelet, and in lung adenocarcinoma cells its inhibition is equivalent to that in the platelet. Inhibition of COX by aspirin in colon cancer cells is in the context of the metastasis of colon cancer primarily to the liver, the organ exposed to the same high concentrations of aspirin as the platelet. We find that the interaction of activated platelets with lung adenocarcinoma cells up-regulates COX-2 expression and PGE2 biosynthesis, and inhibition of platelet COX-1 by aspirin inhibits PGE2 production by the platelet-tumor cell aggregates. In conclusion, low dose aspirin has a significant effect on extraplatelet cyclooxygenase, and potently inhibits COX-2 in lung and colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of metastasis from adenocarcinomas, and particularly from colon adenocarcinomas, by low dose aspirin results from its effect on platelet COX-1 combined with inhibition of PGE2 biosynthesis in metastasizing tumor cells. PMID:27554763

In Vivo Demonstration of PSMA Expression in Adenocarcinoma Urinary Bladder Using 68Ga-PSMA 11 PET/CT.

PubMed

Roy, Shambo Guha; Parida, Girish Kumar; Tripathy, Sarthak; Singhal, Abhinav; Tripathi, Madhavi; Bal, Chandrasekhar

2017-07-01

In vitro and in vivo studies have demonstrated prostate-specific membrane antigen (PSMA) expression in various malignant and benign tumors. Based on the recent immunohistochemical study showing PSMA expression in adenocarcinoma of urinary bladder, we hypothesized that PSMA expression in adenocarcinoma of urinary bladder can be demonstrated in vivo using Ga-PSMA 11 PET/CT. We present a man with exstrophy bladder, presenting with adenocarcinoma urinary bladder referred for staging PET/CT. Both F-FDG and Ga-PSMA-11 PET/CT were done, which showed PSMA expression in the primary tumor as well as metastatic lymph nodes.

Cutaneous metastases of prostatic adenocarcinoma

PubMed Central

Patne, Shashikant C.U.; Naik, Bitan; Patnaik, Pranab; Trivedi, Sameer

2015-01-01

Prostatic adenocarcinoma (PA) is a common visceral malignancy of elderly men. Cutaneous metastasis of PA is rare. The incidence is <1%. A 55-year-old man presented with urinary symptoms and multiple cutaneous nodules around suprapubic region, inner aspect of both thighs and scrotum. Fine-needle aspiration cytology (FNAC) of cutaneous nodules was suggestive of metastatic adenocarcinoma. Skin and prostatic biopsies confirmed the cytological diagnosis. Serum level of prostate specific antigen was raised. Total prostatectomy revealed adenocarcinoma of Gleason's score 7 (3 + 4). Though rare, cutaneous metastases of PA must be known to cytopathologists. Meticulously performed FNAC in such cases may help in early diagnosis. PMID:26229250

Evaluation of Ocoxin®-Viusid® in Metastatic Colorectal Adenocarcinoma

ClinicalTrials.gov

2018-06-15

Colorectal Neoplasm; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasm; Rectal Diseases; Colonic Diseases; Intestinal Disease; Gastrointestinal Disease; Digestive System Disease

Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

ClinicalTrials.gov

2018-02-20

ATM Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Homologous Recombination Deficiency; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

ClinicalTrials.gov

2018-01-29

CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Marginal Zone B Cell Lymphoma); Any T-cell Malignancy; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer); Burkett's Lymphoma; Primary Lymphoma of the Central Nervous System

The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.

PubMed

Dong, Hongmei; Guo, Hong; Xie, Liangxi; Wang, Geng; Zhong, Xueyun; Khoury, Thaer; Tan, Dongfeng; Zhang, Hao

2013-01-01

Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

Massive trapezial metastasis from gastric adenocarcinoma resected and reconstructed with a vascularized scapular bone graft

PubMed Central

Okamoto, Masanori; Yamazaki, Hiroshi; Yoshimura, Yasuo; Aoki, Kaoru; Tanaka, Atsushi; Kato, Hiroyuki

2017-01-01

Abstract Rationale: Isolated metastasis to the hand bones is very rare. Only seven cases of metastasis to the trapezium have been reported. To the best of our knowledge, this is the first report of a single metastasis to the trapezium from a gastric adenocarcinoma. Patient concerns: A 62-year-old man presented with pain and massive swelling in the right carpometacarpal joint of the thumb. Diagnoses: The patient was diagnosed with trapezial metastasis of advanced gastric adenocarcinoma. Interventions: The patient underwent systemic chemotherapy with cisplatin and S-1, radiotherapy to the metastatic bone, and treatment with denosumab. One year later, the huge metastatic tumor was resected, and the hand was reconstructed using vascularized scapular bone. Outcomes: Eighteen months postoperatively, the patient was satisfied with the appearance of the reconstructed hand and was able to use his right thumb in activities of daily living. Lessons: Although rare, metastasis to the trapezium should be considered in patients with persistent and progressive thumb CMC joint pain. PMID:29390390

Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog.

PubMed

Saba, Corey; Ellis, Angela; Cornell, Karen

2011-01-01

A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy.

Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract.

PubMed

O'Connell, Fionnuala P; Wang, Helen H; Odze, Robert D

2005-03-01

Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma. To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas. Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas. Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P = .009, and P < .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups. Estrogen receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are helpful in distinguishing primary gastric carcinomas from metastatic breast carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific for primary gastric carcinomas.

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

PubMed Central

Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

Primary signet ring cell adenocarcinoma of the uterine cervix - A rare neoplasm that raises the question of metastasis to the cervix.

PubMed

Cracchiolo, Bernadette; Kuhn, Theresa; Heller, Debra

2016-04-01

Primary signet ring cell adenocarcinoma is extremely rare. Signet ring cell carcinoma is more commonly primary in the stomach or breast, and the more likely metastatic disease to the cervix needs to be ruled out. We present a case of primary signet ring cell carcinoma of the cervix and review the literature.

Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

ClinicalTrials.gov

2016-07-22

Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

Massive malignant pleural effusion due to lung adenocarcinoma in 13-year-old boy.

PubMed

Afghani, Reza; Hajimohammadi, Amir; Azarhoush, Ramin; Kazemi-Nejad, Vahideh; Yari, Behrouz; Rezapour Esfahani, Mona

2016-05-01

A 13-year-old boy with no risk factors for lung cancer presented with a massive left-sided pleural effusion and a mediastinal shift on chest radiography and computed tomography. A chest tube drained bloody pleural fluid with an exudative pattern. A pleural biopsy and wedge biopsy of the left lower lobe revealed mucinous adenocarcinoma in the left lower lobe wedge biopsy and metastatic adenocarcinoma in the pleural biopsy. The patient is currently undergoing chemotherapy. Radiotherapy is planned after shrinkage of the tumor. Adenocarcinoma of the lung is very rarely seen in teenagers or children, especially in the absence of risk factors. © The Author(s) 2016.

Perioperative Systemic Therapy and Surgery Versus Surgery Alone for Resectable Colorectal Peritoneal Metastases.

ClinicalTrials.gov

2017-05-05

Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer Metastatic; Peritoneal Carcinoma; Peritoneal Neoplasms; Peritoneal Cavity Cancer; Peritoneal Carcinomatosis; Peritoneal Metastases

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

PubMed

Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

2017-02-01

Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Adhesion molecules affected by treatment of lung cancer cells with epidermal growth factor.

PubMed

Fonseca, Fernando L A; Azzalis, Ligia A; Feder, David; Nogoceke, Everson; Junqueira, Virginia B C; Valenti, Vitor E; de Abreu, Luiz Carlos

2011-10-01

Lung cancer is one of the leading causes of death in the world. Some tumor events are attributed to an important group of molecules (cadherins and integrins). We evaluated the interactions of cell adhesion molecules in cell lines from lung cancer. Two lung cancer cell lines were nonmetastatic (H358 and H441) and two were metastatic (H1299 and H292). All cell lines were treated with epidermal growth factor (EGF), and Western blot analysis was performed to assess the interactions between these proteins. The bronchoalveolar cells H358 showed the three analyzed proteins: E-cadherin, β-catenin, and p120 catenin. The adenocarcinoma cells H441 did not present p120 catenin, and carcinoma cells did not show E-cadherin (H1299) or p120 catenin (H292). FAK (pTyr925) was dephosphorylated in adenocarcinoma cells H441, absent in carcinoma cells H1299, and upregulated in the other carcinoma cells H292. p130Cas showed no difference when the cell lines were treated with EGF for 30 min; it was absent in the metastatic carcinoma cells H1299. Paxillin was dephosphorylated in adenocarcinoma cells H441 and also absent in other metastatic carcinoma cells H292. Vinculin showed the same results, and talin was downregulated in adenocarcinoma cells H441 when the cells were treated with EGF. Rap1 was downregulated and PYK2 was upregulated in the same cell line. Our data help to comprehend the mechanism involved in cell migration to the blood and metastasis generation. In conclusion, the expression patterns of cell-cell adhesion were not affected by EGF treatment but it affected cell-extracellular matrix adhesion.

Lectin histochemistry of metastatic adenocarcinomas of the lung.

PubMed

Thöm, Ina; Schult-Kronefeld, Olaf; Burkholder, Iris; Goern, Michael; Andritzky, Birte; Blonski, Katharina; Kugler, Christian; Edler, Lutz; Bokemeyer, Carsten; Schumacher, Udo; Laack, Eckart

2007-06-01

Several clinical studies indicate that primary tumour cells with high metastatic potential often show aberrant glycosylation as detected by lectin histochemistry. However, it is unclear whether aberrant glycosylation is still present in metastatic deposits. The aim of the present investigation was thus to analyse a possible association between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their lymph node and haematogenous metastatic cells. For this purpose, the expression of HPA, PHA-L and UEA-I was assessed in primary tumours, lymph node metastases and haematogenous metastases of 96 patients with metastatic adenocarcinomas of the lung that underwent surgery between 1999 and 2002. Besides, lectin-binding data and other known prognostic factors were correlated with survival. We found a significant positive correlation between the binding of the lectins HPA (p=0.002), PHA-L (p<0.00001) and UEA-I (p<0.00001) to the cells of the primary tumour and to their lymph node metastases. There was a positive correlation between the binding of HPA to the cells of the primary tumour and the haematogenous metastases as well. Patients with tumours which did not show HPA binding sites had a median overall survival of 27.9 months (95%-CI 7.7-infinity months). Patients with a HPA binding tumour had a median overall survival of 20.9 months (95%-CI 18.5-28.7 months). This is the first investigation to demonstrate a positive correlation between the binding of the lectins HPA, PHA-L and UEA-I to the cells of the primary tumour and to their lymph node metastases. Expression of HPA binding sites is also preserved in the haematogenous metastases. In summary, our results support the hypothesis that altered glycosylation of the membrane-bound glycoproteins of the tumour cells is associated with, but not sufficient for promotion of lymphogenic and haematogenous metastasis.

Differentially regulated ADAMTS1, 8, 9, and 18 in pancreas adenocarcinoma

PubMed Central

Aynekin, Büşra; Bozer, Mikdat; Kara, Adem; Haltaş, Hacer; İçen, Duygu; Demircan, Kadir

2017-01-01

Introduction Despite recent diagnostic and therapeutic improvements, pancreas cancer remains one of the highly lethal cancers. The extracellular matrix (ECM) is a physiological barrier that limits the spread of cancer cells into surrounding tissues and distant organs. Disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) is a family of 19 proteases, which is involved in various biological processes such as ECM remodelling and anti-angiogenesis. Aim To investigate the expression of ADAMTS1, 8, 9, and 18 proteinases in pancreas adenocarcinoma and its nodal metastasis. Material and methods The immunostaining status of ADAMTS1, 8, 9, and 18 were investigated in formalin-fixed paraffin-embedded samples of 25 patients who underwent pancreaticoduodenectomy for an adenocarcinoma located at the head of the pancreas. Results In semi-quantitive grading pathologically, ADAMTS1, 8, 9, and 18 were found to be highly stained in all cancerous pancreas samples compared with normal pancreas. In addition, the immune positivity of ADAMTS1, 9, and 18 was found to be higher in metastatic lymph nodes than in non-metastatic lymph tissue. Tumour size was correlated with ADAMTS9 and 18 expressions in cancerous pancreas. Conclusions According to the data obtained from the study, we suggest that these four ADAMTSs may have significant roles in the tumorigenesis and nodal spread of pancreas adenocarcinoma. PMID:29358995

Metastatic Breast Cancer in Uterine Cervix: A Rare Presentation.

PubMed

Proença, Sara; Reis, Maria Inês; Cominho, Joana; Conde, Pedro Casado; Santos E Pereira, Helena; Ribeiro, Filipa Castro

2016-01-01

Uterine cervix involvement by a distant primary tumor is a rare event. We report the following 2 cases of breast tumor metastasis to the uterine cervix with different presentations: case 1 is an isolated cervix metastasis and case 2 is a disseminated metastatic disease with cervix involvement. In both, clinical examination raised the suspicion of cervical tumor, which was confirmed to be a metastatic adenocarcinoma.The poor outcome and lack of symptoms suggest that although its rareness, all patients with breast cancer should undergo a careful routine gynecologic examination.

Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: A phase II Southwest Oncology Group Study (S0415)

PubMed Central

Gold, Philip J.; Goldman, Bryan; Iqbal, Syma; Leichman, Lawrence P.; Zhang, Wu; Lenz, Heinz-Josef; Blanke, Charles D.

2010-01-01

Introduction Esophageal adenocarcinomas commonly express the Epidermal Growth Factor Receptor (EGFR). This trial assessed the six month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second line therapy. Methods This was a multicenter, open-label phase II study of single agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0-2 were required. Patients received cetuximab 400mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. The primary objective was to determine 6 month overall survival. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results Sixty-three patients were registered, with 8 ineligible or never treated. Fifty-five eligible patients (male=49, female=6; median age=61.2 years [range 30.7-88.5]) were enrolled. Twenty patients survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4.0 months (95% CI: 3.2, 5.9). Median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). One partial response and 2 unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of EGFR, EGF, IL-8, COX-2, VEGF, CCND1, NRP1 and Kras mutational status were not associated with response or survival. Conclusions The 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. PMID:20631636

Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin) plus Bevacizumab Chemotherapy

PubMed Central

Naiki, Taku; Etani, Toshiki; Naiki-Ito, Aya; Fujii, Kana; Ando, Ryosuke; Iida, Keitaro; Nagai, Takashi; Sugiyama, Yosuke; Nakagawa, Motoo; Kawai, Noriyasu; Yasui, Takahiro

2017-01-01

The prognostic significance of glandular differentiation in urothelial carcinoma (UC) is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP) and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin) plus bevacizumab (mFOLFOX6+Bev). A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0) by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7) and negativity for cytokeratin 20 (CK20) and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation. PMID:29515396

Calcified miliary brain metastases with mitochondrial inclusion bodies.

PubMed Central

Yamazaki, T; Harigaya, Y; Noguchi, O; Okamoto, K; Hirai, S

1993-01-01

A patient with calcified miliary brain metastases from lung adenocarcinoma is reported. Electron microscopic study of the metastatic tumour cells showed membranous inclusion bodies in mitochondria. Images PMID:8429312

Massive trapezial metastasis from gastric adenocarcinoma resected and reconstructed with a vascularized scapular bone graft: A case report.

PubMed

Okamoto, Masanori; Yamazaki, Hiroshi; Yoshimura, Yasuo; Aoki, Kaoru; Tanaka, Atsushi; Kato, Hiroyuki

2017-12-01

Isolated metastasis to the hand bones is very rare. Only seven cases of metastasis to the trapezium have been reported. To the best of our knowledge, this is the first report of a single metastasis to the trapezium from a gastric adenocarcinoma. A 62-year-old man presented with pain and massive swelling in the right carpometacarpal joint of the thumb. The patient was diagnosed with trapezial metastasis of advanced gastric adenocarcinoma. The patient underwent systemic chemotherapy with cisplatin and S-1, radiotherapy to the metastatic bone, and treatment with denosumab. One year later, the huge metastatic tumor was resected, and the hand was reconstructed using vascularized scapular bone. Eighteen months postoperatively, the patient was satisfied with the appearance of the reconstructed hand and was able to use his right thumb in activities of daily living. Although rare, metastasis to the trapezium should be considered in patients with persistent and progressive thumb CMC joint pain. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma.

PubMed

Pectasides, Eirini; Stachler, Matthew D; Derks, Sarah; Liu, Yang; Maron, Steven; Islam, Mirazul; Alpert, Lindsay; Kwak, Heewon; Kindler, Hedy; Polite, Blase; Sharma, Manish R; Allen, Kenisha; O'Day, Emily; Lomnicki, Samantha; Maranto, Melissa; Kanteti, Rajani; Fitzpatrick, Carrie; Weber, Christopher; Setia, Namrata; Xiao, Shu-Yuan; Hart, John; Nagy, Rebecca J; Kim, Kyoung-Mee; Choi, Min-Gew; Min, Byung-Hoon; Nason, Katie S; O'Keefe, Lea; Watanabe, Masayuki; Baba, Hideo; Lanman, Rick; Agoston, Agoston T; Oh, David J; Dunford, Andrew; Thorner, Aaron R; Ducar, Matthew D; Wollison, Bruce M; Coleman, Haley A; Ji, Yuan; Posner, Mitchell C; Roggin, Kevin; Turaga, Kiran; Chang, Paul; Hogarth, Kyle; Siddiqui, Uzma; Gelrud, Andres; Ha, Gavin; Freeman, Samuel S; Rhoades, Justin; Reed, Sarah; Gydush, Greg; Rotem, Denisse; Davison, Jon; Imamura, Yu; Adalsteinsson, Viktor; Lee, Jeeyun; Bass, Adam J; Catenacci, Daniel V

2018-01-01

Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy. Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37-48. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Janjigian et al., p. 49 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

Esophageal Cancer: New Insights into a Heterogenous Disease.

PubMed

Krug, Sebastian; Michl, Patrick

2017-01-01

Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols. With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved. Several trials confirmed a survival benefit for perioperative chemotherapy or neoadjuvant chemoradiation, respectively, for patients with resectable locally advanced adenocarcinomas. However, the question of whether perioperative chemotherapy or neoadjuvant chemoradiation is more effective for the long-term survival in this population has yet to be fully elucidated. In SCCs, neoadjuvant chemoradiation followed by surgery or definitive chemoradiation in case of functional inoperability represent the preferred treatment options. Compared to neoadjuvant protocols, adjuvant chemotherapy or chemoradiation have only minor effects and are associated with enhanced toxicities. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming to modulate immune check-points and dual inhibition of HER2. In this "to-the-point" article, we review the current standard and summarize the most recent and encouraging therapeutic advances in esophageal cancer. Multimodal treatment approaches for esophageal cancer should be discussed in a multidisciplinary team based on histology, tumor localization, and patient performance status. Neoadjuvant chemoradiation is beneficial for patients with locally advanced SCC and adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ), with perioperative chemotherapy representing a valid alternative for GEJ adenocarcinomas. Combination therapies are indicated for metastatic adenocarcinomas, while the benefit of palliative chemotherapy in SCC remains controversial. Trastuzumab is indicated in HER2+ metastatic adenocarcinomas. © 2017 S. Karger AG, Basel.

Metastatic adenocarcinoma in a young male, 12 years after treatment of primary non seminomatous germ cell tumor

PubMed Central

Coca, Pragnya; Gundeti, Sadashivudu; Uppin, Shantiveer; Digumarti, Raghunadharao

2011-01-01

A man aged 32 years presented with metastatic adenocarcinomatous deposits, 12 years after his initial diagnosis and treatment of immature teratoma of the testis. He was treated for his metastasis with local radiotherapy, failing which he underwent excision of the tumor and palliative chemotherapy. This case is presented for its rarity of occurrence, unique presenting features and difficulty in management. PMID:22174503

A basal stem cell signature identifies aggressive prostate cancer phenotypes

PubMed Central

Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

Utility of GATA3 in the differential diagnosis of pheochromocytoma.

PubMed

Perrino, Carmen M; Ho, Alex; Dall, Christopher P; Zynger, Debra L

2017-09-01

GATA3 is a relatively new immunohistochemical marker which shows consistent nuclear expression in a variety of tumours, including breast and urothelial carcinoma. The staining pattern of GATA3 in adrenal lesions is not well established. We aim to describe the expression of GATA3 in adrenal tumours and determine if there is differential staining between pheochromocytoma and adrenal cortical carcinoma. A retrospective search was performed to identify 74 adrenal lesions which were tested immunohistochemically for GATA3 expression. GATA3 was negative in 90% of adrenal cortical carcinoma. In contrast, pheochromocytomas were frequently positive (71%), including benign pheochromocytoma, pheochromocytoma with features concerning for malignancy, malignant (metastatic) pheochromocytoma and composite pheochromocytoma with ganglioneuroma. Metastatic lung adenocarcinoma in the adrenal gland had occasional (36%) expression, while metastatic clear cell renal cell carcinoma in the adrenal gland did not express GATA3. As the most common pitfall in diagnosing adrenal cortical carcinoma is mistaking it for pheochromocytoma or vice versa, GATA3 may be useful in narrowing the differential diagnosis as a part of a panel of immunohistochemical markers. However, occasional GATA3 expression in the most common source of metastases within the adrenal gland, metastatic pulmonary adenocarcinoma, may confound the diagnosis due to the overlapping expression with pheochromocytoma and other carcinomas. © 2017 John Wiley & Sons Ltd.

[Metastases to the breast from non-mammary malignancies: a clinicopathologic study of 28 cases].

PubMed

Zhou, Shuling; Yu, Baohua; Cheng, Yufan; Xu, Xiaoli; Shui, Ruohong; Bi, Rui; Lu, Hongfen; Tu, Xiaoyu; Yang, Wentao

2014-04-01

To investigate the clinicopathologic characteristics and differential diagnosis of the metastases to the breast from non-mammary malignancies. Twenty-eight cases were collected from 2004 to 2012;microscopic pathologic examinations and immunohistochemistry (EnVision method) were performed. (1) All except one patients were female, ranging from 16 to 77 years old (average 45.8 years). Twenty-six (92.9%) patients initially presented with the primary site lesions; while the other two (7.1%) patients initially presented with breast lesions. The mean interval from primary diagnosis to detection of metastatic breast lesions was 32 months (0-228 months). Fifteen patients (53.6%) had other metastases detected simultaneously or preceded the breast lesions. (2) Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 4.0 cm (0.6-12.0 cm). The histological types of the corresponding primary tumors were as follows: eight (28.6%) cases from lung adenocarcinoma, five (17.8%) from high-grade ovarian serous carcinoma, three (10.7%) from gastric adenocarcinoma, two (7.1%) from rectal adenocarcinoma, one (3.6%) from pancreatic neuroendocrine carcinoma, one (3.6%) from prostatic carcinoma, four (14.3%) from melanoma, and four (14.3%) from mesenchymal malignant tumors (three rhabdomyosarcomas and one epithelioid malignant peripheral nerve sheath tumor, MPNST). (3) Histologically, the metastatic tumors showed the morphologic characteristics of the primary tumors. Lymph-vascular invasion was observed in 19 cases. Immunohistochemical features of metastatic tumors were consistent with the primary tumors. Molecular markers for breast such as GCDFP15 and mammaglobin were negative. Metastatic tumors from lung adenocarcinoma expressed TTF-1 (8/8). Ovarian serous carcinoma metastases were positive for PAX8 (5/5) and WT1 (4/5). Gastric adenocarcinoma metastases were positive for CDX2 (3/3) and villin (1/3). Rectal adenocarcinoma metastases were positive for CDX2 (2/2). Pancreatic neuroendocrine tumor metastasis was positive for Syn and CgA (both 1/1). Prostate carcinoma metastasis was positive for AR, PSA and P504S (all 1/1). Melanoma metastases were positive for HMB45 (2/3) and S-100 protein (3/3). Rhabdomyosarcoma metastases were positive for vimentin, desmin and myoD1 (all 3/3). MPNST metastasis was positive for S-100 protein (1/1). (4) Follow-up data was available in 17 patients, with median follow-up time 54 months. The median survival from diagnosis to breast metastasis was 24 months.Seven of 17 patients died. Metastases to the breast from non-mammary malignancies are rare and show pathologic features of primary tumors. It is usually presumed to be a primary breast carcinoma. Histopathologic features and clinical history in conjunction with the immunohistochemical results should be considered in differentiating a secondary mass from a primary breast carcinoma.

Palatine tonsillar metastasis of a small pulmonary adenocarcinoma showing an invasive micropapillary carcinoma pattern and Pagetoid spread at the tonsil: a case suggesting retrograde lymphatic metastasis from bulky lymph node metastases of the neck.

PubMed

Tajima, Shogo; Koda, Kenji

2015-01-01

Metastasis rarely occurs in the palatine tonsils. Among primary pulmonary carcinoma subtypes, small cell carcinoma more frequently metastasizes to this site. Herein, we present an exceedingly rare case of a small pulmonary adenocarcinoma that metastasized to the cervical lymph nodes and the right palatine tonsil in a 62-year-old man. In spite of the small size of the primary site, such extensive metastasis may have occurred because of the invasive micropapillary carcinoma pattern seen in the metastatic sites. The manner of metastasis to the palatine tonsil was considered retrograde lymphatic metastasis originating from carcinoma cells in the cervical lymph nodes. Furthermore, Pagetoid spread was observed at the palatine tonsil. Although there have been only a few cases showing retrograde lymphatic metastasis and Pagetoid spread at the metastatic site, we should be careful when speculating about the primary site based on such metastatic sites, especially when dealing with a biopsy sample exhibiting Pagetoid spread.

EML4-ALK-positive lung adenocarcinoma presenting an unusual metastatic pattern in a 29-year-old woman who is alive and well in her third year follow up:A case report.

PubMed

Tokat, Fatma; Zeren, Handan; Barut, Pinar; Tansan, Sualp; Ince, Umit

2017-01-01

Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman. Young adult non-smoker female patients with an unexplained pleural effusion and signs of metastatic disease should alert the physicians straight away for all types of malignancies including lung cancer. Any skin lesions should be evaluated carefully, biopsies should be done to exclude metastasis in urgency. On the other hand, an uncommon clinical presentation of a lung cancer requires corresponding molecular testing rapidly in order to offer the best treatment option.

Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

ClinicalTrials.gov

2018-04-02

Clear Cell Renal Cell Carcinoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Penile Carcinoma; Renal Pelvis Urothelial Carcinoma; Squamous Cell Carcinoma of the Penis; Stage III Bladder Adenocarcinoma AJCC v6 and v7; Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Penile Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Renal Pelvis Cancer AJCC v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IIIa Penile Cancer AJCC v7; Stage IIIb Penile Cancer AJCC v7; Stage IV Bladder Adenocarcinoma AJCC v7; Stage IV Bladder Squamous Cell Carcinoma AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Penile Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma

Silencing the hsp25 Gene Eliminates Migration Capability of the Highly Metastatic Murine 4T1 Breast Adenocarcinoma Cell

PubMed Central

Bausero, Maria A.; Bharti, Ajit; Page, Diana T.; Perez, Kristen D.; Eng, Jason W.-L.; Ordonez, Susana L.; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

2006-01-01

The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. PMID:16340246

Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell.

PubMed

Bausero, Maria A; Bharti, Ajit; Page, Diana T; Perez, Kristen D; Eng, Jason W-L; Ordonez, Susana L; Asea, Edwina E; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

2006-01-01

The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. Copyright 2006 S. Karger AG, Basel.

The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology.

PubMed

Ferrone, Cristina R; Ting, David T; Shahid, Mohammed; Konstantinidis, Ioannis T; Sabbatino, Francesco; Goyal, Lipika; Rice-Stitt, Travis; Mubeen, Ayesha; Arora, Kshitij; Bardeesey, Nabeel; Miura, John; Gamblin, T Clark; Zhu, Andrew X; Borger, Darrell; Lillemoe, Keith D; Rivera, Miguel N; Deshpande, Vikram

2016-01-01

Intrahepatic cholangiocarcinoma (ICC) often is a diagnosis determined by exclusion. Distinguishing ICC from other metastatic adenocarcinomas based on histopathologic or immunohistochemical analysis often is difficult and requires an extensive workup. This study aimed to determine whether albumin, whose expression is restricted to the liver, has potential as a biomarker for ICC using a novel and highly sensitive RNA in situ hybridization (ISH) platform. Modified branched DNA probes were developed for albumin RNA ISH. The study evaluated 467 patient samples of primary and metastatic lesions. Of the 467 samples evaluated, 83 were ICCs, 42 were hepatocellular carcinomas (HCCs), and 332 were nonhepatic carcinomas including tumors arising from the perihilar region and bile duct, pancreas, stomach, esophagus, colon, breast, ovary, endometrium, kidney, and urinary bladder. Albumin RNA ISH was highly sensitive for cancers of liver origin, staining positive in 82 (99 %) of 83 ICCs and in 42 HCCs (100 %). Perihilar and distal bile duct carcinomas as well as carcinomas arising at other sites tested negative for albumin. Notably, 6 (22 %) of 27 intrahepatic tumors previously diagnosed as carcinomas of undetermined origin tested positive for albumin. Albumin RNA ISH is a sensitive and highly specific diagnostic tool for distinguishing ICC from metastatic adenocarcinoma to the liver or carcinoma of unknown origin. Albumin RNA ISH could replace the extensive diagnostic workup, leading to timely confirmation of the ICC diagnosis. Additionally, the assay could serve as a guide to distinguish ICC from perihilar adenocarcinoma.

A case of rectal carcinoma with skin and bone marrow metastasis with concurrent extensive visceral involvement; unusual and dismal co-incidence.

PubMed

Arslan, Cagatay; Sen, Cenk Ahmet; Ortac, Ragip

2015-06-01

Novel systemic therapies and modern surgical and ablative approaches have improved the survival rates for the patients with metastatic colorectal cancer. However, there are still patients with poor prognosis and underlying mechanisms that could not be defined clearly. Metastatic colorectal cancer patients with skin metastasis have a poor prognosis. A 45-year-old man, who presented with large bowel obstruction, was diagnosed with metastatic rectal adenocarcinoma. Unresectable liver metastases were found at diagnosis. FOLFOX plus bevacizumab treatment was started, but the patient developed bowel obstruction after the third cycle. Therefore, ileostomy was performed. Multiple skin, lung, liver and bone metastases appeared during that time. Bone marrow biopsy demonstrated diffuse infiltration by adenocarcinoma cells. Even though partial remission was achieved after 4 cycles of FOLFIRI-cetuximab, the disease progressed after the 8th cycle. The patient lost his life due to disease progression 8 months after the diagnosis. Bone marrow and skin are unusual sites of metastasis for colorectal carcinoma. Metastases in bone marrow and skin develop at later stages of metastatic disease. This patient lived only 4 months after the development of skin and bone marrow metastases. Skin and bone marrow metastases may be the harbingers of short survival. Biopsy of metastatic sites is crucial for diagnosis and detailed molecular analysis. Molecular pathway alterations underlying worse disease course may be found, and hence probable targets for drug improvement may be indicated.

Lipid-laden macrophage infiltration of human adenocarcinoma in vivo associated with taxol and GCSF treatment.

PubMed

Abramson, N; Castro, S; Goldstein, J D

1997-01-01

This brief report illustrates the presence of lipid-laden macrophages in proximity to metastatic adenocarcinoma cells within the bone marrow of a patient receiving taxol and GCSF therapy. The pathophysiological mechanism is uncertain. Taxol, which is associated with macrophage function in vitro, may have been responsible for the recruitment of macrophages in this patient. GCSF could have contributed as well; however, GCSF usually has little effect on monocytes and macrophages.

Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma

PubMed Central

Azzopardi, Stephanie; Smith, Roger S.; Nasar, Abu; Altorki, Nasser K.; Mittal, Vivek; Somwar, Romel; Stiles, Brendon M.; Du, Yi-Chieh Nancy

2016-01-01

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers, but its role in primary and metastatic non-small cell lung carcinoma (NSCLC) remains to be determined. Here, we investigate the clinical relevance of RHAMM expression in NSCLC. RHAMM protein expression correlates with histological differentiation stages and extent of the primary tumor (T stages) in 156 patients with primary NSCLC. Importantly, while focal RHAMM staining pattern is present in 57% of primary NSCLC, intense RHAMM protein expression is present in 96% of metastatic NSCLC cases. In a publicly available database, The Cancer Genome Atlas (TCGA), RHAMM mRNA expression is 12- and 10-fold higher in lung adenocarcinoma and squamous lung carcinoma than in matched normal lung tissues, respectively. RHAMM mRNA expression correlates with stages of differentiation and inferior survival in more than 400 cases of lung adenocarcinoma in the Director's Challenge cohort. Of 4 RHAMM splice variants, RHAMMv3 (also known as RHAMMB) is the dominant variant in NSCLC. Moreover, shRNA-mediated knockdown of RHAMM reduced the migratory ability of two lung adenocarcinoma cell lines, H1975 and H3255. Taken together, RHAMM, most likely RHAMMv3 (RHAMMB), can serve as a prognostic factor for lung adenocarcinomas and a potential therapeutic target in NSCLC to inhibit tumor migration. PMID:27220886

VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

ClinicalTrials.gov

2014-10-10

Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis

PubMed Central

James, Mathews; Amaranathan, Anandhi; Nelamangala Ramakrishnaiah, Vishnu Prasad; Toi, Pampa Chakrabarty

2016-01-01

Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care. PMID:27312852

Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

PubMed

2015-10-01

The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

Aspiration cytology of extramammary tumours metastatic to the breast.

PubMed

Handa, Uma; Chhabra, Seema; Mohan, Harsh

2007-10-01

This study was undertaken to highlight the use of fine needle aspiration cytology (FNAC) to distinguish tumours metastatic to the breast from primary breast malignancies. A total of 1866 fine needle aspirates of the breast were performed during a period of 7 years. Three hundred and fourteen cases of breast malignancies were diagnosed and 5 (1.5%) out of these cases were metastatic in origin. The metastatic tumors included, 2 cases of malignant melanoma (chest wall and left arm), 1 case each of haematolymphoid malignancy, adenocarcinoma of the ovary, and squamous cell carcinoma (left leg). FNA diagnosis of metastasis to the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.

Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

PubMed Central

Gill, C. W.

1981-01-01

A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

Identification of Genes Required for the Survival of Prostate Cancer Cells

DTIC Science & Technology

2011-06-01

metastatic cancers (3). In contrast to localized prostate tumors, metastatic prostate cancer has only a 32% 5-year survival rate (4). For sustained...of the brain (34) and is p53-, p16-, and pRb- mutated (31). The PC-3 adenocarcinoma cell line was obtained from a grade IV androgen-independent...receptor-gamma ( PPAR -gamma) (52), both of which have been previously implicated in prostate cancer disease progression. 
 10
 A. B

Sorafenib in Treating Patients With Regional or Metastatic Cancer of the Urothelium

ClinicalTrials.gov

2014-05-20

Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

PubMed

Markóczy, Zsolt; Sárosi, Veronika; Kudaba, Iveta; Gálffy, Gabriella; Turay, Ülkü Yilmaz; Demirkazik, Ahmet; Purkalne, Gunta; Somfay, Attila; Pápai-Székely, Zsolt; Rásó, Erzsébet; Ostoros, Gyula

2018-05-25

Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. ClinicalTrials.gov Identifier: NCT01609543.

[Adenocarcinoma of minor salivary gland origin: a recently described lesion. A case report].

PubMed

Advenier, Anne-Sophie; Poupart, Marc; Devouassoux-Shisheboran, Mojgan; Barnoud, Raphaëlle

2013-12-01

Cribriform adenocarcinoma of salivary gland origin is a rare and recently described lesion. In spite of the high incidence of metastatic spread, the prognosis remains very good. We report a case of a 64-year-old man with cribriform adenocarcinoma of salivary gland origin of the ventral tongue without locoregional or distant metastasis. The patient is currently 43-month post treatment without any local or regional recurrence of the disease. This entity should be kept in mind regarding its good prognosis and its resemblances with papillary carcinoma of the thyroid and adenoid cystic carcinoma with which it should not be confused. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ClinicalTrials.gov

2018-06-27

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Rare Disorder; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm; Squamous Cell Carcinoma of the Penis; Teratoma With Malignant Transformation; Testicular Non-Seminomatous Germ Cell Tumor; Thyroid Gland Carcinoma; Tracheal Carcinoma; Transitional Cell Carcinoma; Undifferentiated Gastric Carcinoma; Ureter Adenocarcinoma; Ureter Squamous Cell Carcinoma; Urethral Adenocarcinoma; Urethral Squamous Cell Carcinoma; Vaginal Adenocarcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified; Vulvar Carcinoma

Gastric type mucinous endocervical adenocarcinoma of the uterine cervix: very rare and interesting case.

PubMed

Park, Chul Min; Koh, Hyun Min; Park, Soyun; Kang, Hye Sim; Shim, Soon Sup; Kim, Sung Yob

2018-01-01

Gastric type mucinous endocervical adenocarcinomas of the uterine cervix (GAC) are a newly classified mucinous subtype with morphologically in 2014, WHO. They have a much more aggressiveness and show unusual metastatic patterns compared to usual type endocervical adenocarcinoma. They tend to present at higher stage and even in stage I, they have worse survival. Therefore, differential diagnosis of GAC from the usual type of endocervical adenocarcinoma is very important because they are related to a significant risk of recurrence and decreased 5-year disease-specific survival. Besides, GACs are mostly not associated with human papillomavirus (HPV) infection and p16 immunohistochemistry is also typically negative in GAC that is HPV-unassociated tumor. We report a very rare and interesting case of stage IB1 GAC with negative HPV DNA and p16.

Magnetic resonance imaging-guided focused laser interstitial thermal therapy for subinsular metastatic adenocarcinoma: technical case report.

PubMed

Hawasli, Ammar H; Ray, Wilson Z; Murphy, Rory K J; Dacey, Ralph G; Leuthardt, Eric C

2012-06-01

To describe the novel use of the AutoLITT System (Monteris Medical, Winnipeg, Manitoba, Canada) for focused laser interstitial thermal therapy (LITT) with intraoperative magnetic resonance imaging (MRI) and stereotactic image guidance for the treatment of metastatic adenocarcinoma in the left insula. The patient was a 61-year-old right-handed man with a history of metastatic adenocarcinoma of the colon. He had previously undergone resection of multiple lesions, Gamma Knife radiosurgery, and whole-brain radiation. Despite treatment of a left insular tumor, serial imaging revealed that the lesion continued to enlarge. Given the refractory nature of this tumor to radiation and the deep-seated location, the patient elected to undergo LITT treatment. The center of the lesion and entry point on the scalp were identified with STEALTH (Medtronic, Memphis, Tennessee) image-guided navigation. The AXiiiS Stereotactic Miniframe (Monteris Medical) for the LITT system was secured onto the skull, and a trajectory was defined to achieve access to the centroid of the tumor. After a burr hole was made, a gadolinium template probe was inserted into the AXiiiS base. The trajectory was confirmed via an intraoperative MRI, and the LITT probe driver was attached to the base and CO2-cooled, side-firing laser LITT probe. The laser was activated and thermometry images were obtained. Two trajectories, posteromedial and anterolateral, produced satisfactory tumor ablation. LITT with intraoperative MRI and stereotactic image guidance is a newly available, minimally invasive, and therapeutically viable technique for the treatment of deep seated brain tumors.

Periportal low attenuation associated with liver metastasis from colorectal cancer: evaluation using multi-detector-row CT with pathological correlation.

PubMed

Takaji, Ryo; Matsumoto, Shunro; Kiyonaga, Maki; Yamada, Yasunari; Mori, Hiromu; Iwashita, Yukio; Ohta, Masayuki; Inomata, Masafumi; Hijiya, Naoki; Moriyama, Masatsugu; Takaki, Hajime; Fukuzawa, Kengo; Yonemasu, Hirotoshi

2017-01-01

Periportal low attenuation (PPLA) associated with metastatic liver cancer is occasionally seen on multi-detector-row CT (MDCT). The purpose of this study was to investigate the MDCT patterns of the PPLA and to correlate it with pathological findings. We retrospectively reviewed the MDCT images of 63 patients with metastatic liver cancers from colorectal adenocarcinoma. On MDCT scans, PPLA associated with liver metastasis was visualized in six patients with colorectal cancer. In these six patients who had undergone surgical resection, the radiologic-pathologic correlation was analyzed. All patients underwent a single contrast-enhanced MDCT within 1 month before surgical resection. The six liver cancers were pathologically proven to be moderately differentiated adenocarcinoma. We assessed the PPLA on MDCT concerning the distribution patterns and contrast enhancement with pathological correlation. In five of the patients, the PPLA extended to the hilar side from metastatic liver cancer. Pathologically, there was no cancer invasion into the intra-hepatic periportal area; however, massive lymphedema and fibrosis occurred in all six cases. PPLA on the hilar and peripheral sides of hepatic metastasis from colorectal cancer may be present suggesting lymphedema and fibrosis of portal tracts not always indicating cancer infiltration.

Laparoscopic Surgery of Urachal Anomalies: A Single-Center Experience.

PubMed

Sukhotnik, Igor; Aranovich, Igor; Mansur, Bshara; Matter, Ibrahim; Kandelis, Yefim; Halachmi, Sarel

2016-11-01

The traditional surgical approach to the excision of persistent urachal remnants is a lower midline laparotomy or semicircular infraumbilical incision. To report our experience with laparoscopic/open urachus excision as a minimally invasive diagnostic and surgical technique. This was a retrospective study involving patients who were diagnosed with persistent urachus and underwent laparoscopic/open excision. The morbidity, recovery, and outcomes of surgery were reviewed. Eight patients (males:females 6:2) with an age range of 1 month to 17 years underwent laparoscopic or open excision (six and two patients respectively). All patients presented with discharge from the umbilicus. Although three patients had no sonographic evidence of a patent urachus, diagnostic laparoscopy detected a patent urachus that was excised laparoscopically. The operative time of laparoscopic surgery ranged from 19 to 71 minutes (the last case was combined with bilateral laparoscopic inguinal hernia repair), and the mean duration of hospital stay was 2.0 ± 0.36 days. Pathological examination confirmed a benign urachal remnant in all cases. Laparoscopy is a useful alternative for the management of persistent or infected urachus, especially when its presence is clinically suspected despite the lack of sonographic evidence. The procedure is associated with low morbidity, although a small risk of bladder injury exists, particularly in cases of severe active inflammation.

A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

PubMed

Shah, Manish A; Power, Derek G; Kindler, Hedy L; Holen, Kyle D; Kemeny, Margaret M; Ilson, David H; Tang, Laura; Capanu, Marinela; Wright, John J; Kelsen, David P

2011-12-01

The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.

Smad4/Fascin index is highly prognostic in patients with diffuse type EBV-associated gastric cancer.

PubMed

Son, Byoung Kwan; Kim, Dong-Hoon; Min, Kyueng-Whan; Kim, Eun-Kyung; Kwon, Mi Jung

2018-04-01

Gastric cancer is a heterogeneous disorder for which predicting clinical outcomes is challenging, although various biomarkers have been suggested. The Smad4 and Fascin proteins are known prognostic indicators of different types of malignancy. Smad4 primarily functions as a key regulator of tumor suppression, whereas Fascin exhibits oncogenic function by enhancing tumor infiltration. A combined marker based on these opposing roles may improve prognostic accuracy in gastric cancer. Smad4 and Fascin expression was assessed in tissue microarrays obtained from 285 primary gastric adenocarcinoma, 201 normal tissue, and 51 metastatic adenocarcinoma samples. A Smad4/Fascin index based on the relative expression of each protein was divided into low- and high-expression groups using receiver operating characteristic curves. We compared normal tissue, primary adenocarcinoma, and metastatic adenocarcinoma in Smad4 and Fascin expression and the differences in clinicopathological findings between low Smad4/Fascin and high Smad4/Fascin expression in gastric adenocarcinoma. High Smad4/Fascin expression was significantly associated with worse outcomes, such as old age, advanced T and N category, large tumor size, high histological grade, lymphatic and vascular invasion, and presence of Epstein-Barr virus (EBV) (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and Smad4/Fascin index in diffuse-type or EBV-associated gastric cancer (all p < 0.05). A dual marker system using Smad4 and Fascin may be a reliable indicator for predicting clinical outcomes in patients with diffuse-type or EBV-associated gastric cancer. Copyright © 2018 Elsevier GmbH. All rights reserved.

Adenocarcinoma of the thymus, enteric type: report of 2 cases, and proposal for a novel subtype of thymic carcinoma.

PubMed

Moser, Bernhard; Schiefer, Ana Iris; Janik, Stefan; Marx, Alexander; Prosch, Helmut; Pohl, Wolfgang; Neudert, Barbara; Scharrer, Anke; Klepetko, Walter; Müllauer, Leonhard

2015-04-01

We report 2 cases of primary thymic adenocarcinoma with enteric differentiation. One carcinoma occurred in a 41-year-old man as a 7-cm-diameter cystic tumor and the other one in a 39-year-old woman as a 6-cm-diameter solid mass. Both tumors were located in the anterior mediastinum. Clinical staging did not reveal any extrathymic tumor. Histologically, the tumors were classified as adenocarcinoma, not otherwise specified, and a mucinous (colloid) carcinoma, respectively. Immunohistochemically, both tumors were positive for cytokeratin 20 (CK20), CDX2, and carcinoembryonic antigen, reflecting enteric differentiation. A review of the literature on 43 other cases of primary thymic adenocarcinomas suggested 11 further cases with enteric differentiation, as assessed by CK20 and/or CDX2 expression. We propose that thymic adenocarcinoma with enteric differentiation represents a novel subtype of thymic carcinoma. It is mostly of mucinous morphology and frequently associated with thymic cysts. The clinical outcome is variable. Recognition of primary thymic adenocarcinoma with enteric differentiation is helpful for the differentiation from metastatic disease, mainly from the gastrointestinal tract.

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma.

PubMed

Chung, Yumin; Wi, Young Chan; Kim, Yeseul; Bang, Seong Sik; Yang, Jung-Ho; Jang, Kiseok; Min, Kyueng-Whan; Paik, Seung Sam

2018-01-01

Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. Combined expression patterns based on Smad4+/- and PTEN+/- status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. Smad4-/PTEN- status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4-/PTEN- and Smad4+/PTEN+ groups were compared, Smad4-/PTEN- status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4-/PTEN+ or Smad4+/PTEN-, and Smad4-/PTEN-) (all p<.05). Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

Fulminant abdominal gas gangrene in metastatic colon cancer.

PubMed

Bozkurt, Mustafa; Okutur, Kerem; Aydin, Kübra; Namal, Esat; Oztürk, Akin; Balci, Cem; Demir, Gökhan

2012-02-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms.

Smad4 Loss in Esophageal Adenocarcinoma Is Associated With an Increased Propensity for Disease Recurrence and Poor Survival

PubMed Central

Singhi, Aatur D.; Foxwell, Tyler J.; Nason, Katie; Cressman, Kristi L.; McGrath, Kevin M.; Sun, Weijing; Bahary, Nathan; Zeh, Herbert J.; Levy, Ryan M.; Luketich, James D.; Davison, Jon M.

2015-01-01

Previously regarded as a rare neoplasm, the incidence of esophageal adenocarcinoma has risen rapidly in recent decades. It is often discovered late in the disease process and has a dismal prognosis. Current prognostic markers including clinical, radiographic, and histopathologic findings have limited utility and do not consider the biology of this deadly disease. Genome-wide analyses have identified SMAD4 inactivation in a subset of tumors. Although Smad4 has been extensively studied in other gastrointestinal malignancies, its role in esophageal adenocarcinoma remains to be defined. Herein, we show, in a large cohort of esophageal adenocarcinomas, Smad4 loss by immunohistochemistry in 21 of 205 (10%) tumors and that Smad4 loss correlated with increased postoperative recurrence (P=0.040). Further, patients whose tumors lacked Smad4 had shorter time to recurrence (TTR) (P=0.007) and poor overall survival (OS) (P=0.011). The median TTR and OS of patients with Smad4-negative tumors was 13 and 16 months, respectively, as compared with 23 and 22 months, respectively, among patients with Smad4-positive tumors. In multivariate analyses, Smad4 loss was a prognostic factor for both TTR and OS, independent of histologic grade, lymphovascular invasion, perineural invasion, tumor stage, and lymph node status. Considering Smad4 loss correlated with postoperative locoregional and/or distant metastases, Smad4 was also assessed in a separate cohort of 5 locoregional recurrences and 43 metastatic esophageal adenocarcinomas. In contrast to primary tumors, a higher prevalence of Smad4 loss was observed in metastatic disease (44% vs. 10%). In summary, loss of Smad4 protein expression is an independent prognostic factor for TTR and OS that correlates with increased propensity for disease recurrence and poor survival in patients with esophageal adenocarcinoma after surgical resection. PMID:25634752

Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

ClinicalTrials.gov

2018-05-30

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

ClinicalTrials.gov

2018-05-23

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Peritoneal mucinous cystadenocarcinoma of probable urachal origin: a challenging diagnosis

PubMed Central

Gore, D M; Bloch, S; Waller, W; Cohen, P

2006-01-01

This report describes the case of a mucinous cystadenocarcinoma of probable urachal origin that presented with mass effect, precipitating deep venous thrombosis and pulmonary embolism. The patient presented with acute symptoms of leg swelling, pain and dyspnoea, and a vague awareness of lower abdominal distension. Computer tomography showed a cystic mass closely related to the anterior abdominal wall and the superior aspect of the bladder. A 1500 cm3 cyst adherent to the dome of the urinary bladder was resected on laparotomy. Partial cystectomy was not carried out in the belief that the cyst represented a benign lesion. Subsequent imaging has shown cystic changes in the anterior bladder wall, and the patient has been referred for partial cystectomy. PMID:17021133

Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

ClinicalTrials.gov

2018-04-11

Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

Umbilical metastasis or Sister Mary Joseph's nodule as a very early sign of an occult cecal adenocarcinoma.

PubMed

Salemis, Nikolaos S

2007-01-01

Umbilical metastasis (Sister Mary Joseph's nodule) is a rare occurrence and indicates, in most of the patients, an advanced intraabdominal malignancy. It may be the first sign of an underlying adenocarcinoma, originating mainly from the gastrointestinal or genitourinary tract. An extremely rare case of a Sister Mary Joseph's nodule is described herein, where the metastatic umbilical nodule was the first sign of a cecal adenocarcinoma and became evident 8 months before the onset of the disease. Diagnostic evaluation and surgical management are discussed along with a review of the literature. This case is presented in order to emphasize the need for thorough investigation of any umbilical lesion especially in elderly patients.

Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2014-09-08

Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer

Epithelioid malignant mesothelioma metastatic to the skin: A case report and review of the literature.

PubMed

Ward, Rachel Elizabeth; Ali, Stefanie Ann; Kuhar, Matthew

2017-12-01

Malignant mesothelioma (MM) is an aggressive and invasive neoplasm primarily affecting the pleura, peritoneum and pericardium. While mesothelioma commonly metastasizes to visceral organs, it has rarely been documented to involve the skin and subcutaneous tissue. There is a paucity of reports of cutaneous metastatic mesothelioma, and histologic examination is often challenging because the tumor closely mimics other primary and metastatic neoplasms. We report a case of a 75-year-old man presenting with a firm, hard nodule on his upper back, which on initial histologic evaluation resembled metastatic adenocarcinoma. However, upon review of his medical history and immunohistochemical evaluation of the lesion, the diagnosis of epithelioid MM metastatic to the skin was rendered. The purpose of this case report and review of the literature is to summarize the most effective available immunostains to aid in the diagnosis of this challenging entity, highlight the histologic similarities between metastatic epithelioid MM and other primary and metastatic neoplasms of the skin, and provide prognostic information for these rare tumors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prostate carcinoma mimicking a sphenoid wing meningioma

PubMed Central

Bradley, Lucas H.; Burton, Matthew; Gokden, Murat; Serletis, Demitre

2015-01-01

Introduction We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. Presentation of case An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Discussion Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). Conclusion We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. PMID:26318129

Mucin profiles in signet-ring cell carcinoma.

PubMed

Nguyen, Minh D; Plasil, Brian; Wen, Ping; Frankel, Wendy L

2006-06-01

Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.

Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

PubMed

Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

2017-02-01

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

PubMed Central

Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

2014-01-01

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

PubMed

Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

2015-02-01

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. © 2014 by The Author(s).

Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer.

PubMed

Yang, X J; Lecksell, K; Gaudin, P; Epstein, J I

1999-02-01

Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.

Phospholipid ether analogs for the detection of colorectal tumors.

PubMed

Deming, Dustin A; Maher, Molly E; Leystra, Alyssa A; Grudzinski, Joseph P; Clipson, Linda; Albrecht, Dawn M; Washington, Mary Kay; Matkowskyj, Kristina A; Hall, Lance T; Lubner, Sam J; Weichert, Jamey P; Halberg, Richard B

2014-01-01

The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×10(10) vs 3.27×10(9) respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.

Overexpression of microRNA-95-3p suppresses brain metastasis of lung adenocarcinoma through downregulation of cyclin D1.

PubMed

Hwang, Su Jin; Lee, Hye Won; Kim, Hye Ree; Song, Hye Jin; Lee, Dong Heon; Lee, Hong; Shin, Chang Hoon; Joung, Je-Gun; Kim, Duk-Hwan; Joo, Kyeung Min; Kim, Hyeon Ho

2015-08-21

Despite great efforts to improve survival rates, the prognosis of lung cancer patients is still very poor, mainly due to high invasiveness. We developed brain metastatic PC14PE6/LvBr4 cells through intracardiac injection of lung adenocarcinoma PC14PE6 cells. Western blot and RT-qPCR analyses revealed that PC14PE6/LvBr4 cells had mesenchymal characteristics and higher invasiveness than PC14PE6 cells. We found that cyclin D1 was upregulated, miR-95-3p was inversely downregulated, and pri-miR-95 and its host gene, ABLIM2, were consistently decreased in PC14PE6/LvBr4 cells. MiR-95-3p suppressed cyclin D1 expression through direct binding to the 3' UTR of cyclin D1 mRNA and suppressed invasiveness, proliferation, and clonogenicity of PC14PE6/LvBr4 cells. Ectopic cyclin D1 reversed miR-95-3p-mediated inhibition of invasiveness and clonogenicity, demonstrating cyclin D1 downregulation is involved in function of miR-95-3p. Using bioluminescence imaging, we found that miR-95-3p suppressed orthotopic tumorigenicity and brain metastasis in vivo and increased overall survival and brain metastasis-free survival. Consistent with in vitro metastatic cells, the levels of miR-95-3p, pri-miR-95, and ABLIM2 mRNA were decreased in brain metastatic tissues compared with lung cancer tissues and higher cyclin D1 expression was involved in poor prognosis. Taken together, our results demonstrate that miR-95-3p is a potential therapeutic target for brain metastasis of lung adenocarcinoma cells.

Phospholipid Ether Analogs for the Detection of Colorectal Tumors

PubMed Central

Deming, Dustin A.; Maher, Molly E.; Leystra, Alyssa A.; Grudzinski, Joseph P.; Clipson, Linda; Albrecht, Dawn M.; Washington, Mary Kay; Matkowskyj, Kristina A.; Hall, Lance T.; Lubner, Sam J.; Weichert, Jamey P.; Halberg, Richard B.

2014-01-01

The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×1010 vs 3.27×109 respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease. PMID:25286226

Helicobacter Species Identified in Captive Sooty Mangabeys (Cercocebus atys) with Metastatic Gastric Adenocarcinoma

PubMed Central

Esmail, Michael Y.; Bacon, Rebecca; Swennes, Alton G.; Feng, Yan; Shen, Zeli; Garcia, AnaPatricia; Sharma, Prachi; Cohen, Joyce; Fox, James G.

2016-01-01

Background Of all human cancers, gastric carcinoma is the one of the leading causes of death. Helicobacter pylori is considered a major etiologic agent of this disease. Spontaneously occurring gastric carcinoma is a rare diagnosis in nonhuman primates. A 2011 case report documented a high incidence of gastric adenocarcinoma in a closed colony of captive sooty mangabeys (Cercebus atys). However, H. pylori infection was not detected in these animals. Materials and Methods In this study, using archived formalin-fixed, paraffin-embedded stomach sections of these animals alternative methodologies were used to identify H. pylori and other non-H. pylori Helicobacter species. In addition, two additional cases of sooty mangabeys with metastatic gastric carcinoma are characterized. Results Using fluorescent in situ hybridization, we identified gastric H. suis in 75% of archived and new gastric carcinoma cases. In the two newly reported cases, H. suis and a novel Helicobacter species were detected via PCR and sequence analysis of the 16S rRNA gene. H. pylori was not identified in any of the gastric carcinoma cases via FISH and/or PCR and sequence analysis of Helicobacter spp. in DNA from of available tissues. Conclusions This report is the first to characterize Helicobacter species infection in spontaneous gastric carcinoma with metastatic potential in nonhuman primates. PMID:26477442

Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999-2013).

PubMed

McQuown, B; Keyerleber, M A; Rosen, K; McEntee, M C; Burgess, K E

2017-09-01

Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252-448 days). Median progression free survival was 289 days (range: 224-469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC. © 2016 John Wiley & Sons Ltd.

Metastatic iridociliary adenocarcinoma in a labrador retriever.

PubMed

Zarfoss, M K; Dubielzig, R R

2007-09-01

An enucleated left eye from a 15-year-old female spayed Labrador Retriever was received by the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for histopathologic evaluation. Routine histologic preparation included staining with hematoxylin and eosin, and with alcian blue periodic acid-Schiff (PAS). At necropsy 9 months later, all grossly abnormal tissues (ipsilateral orbit and lung) were submitted to the COPLOW for histopathologic evaluation. Histopathologic evaluation of the globe revealed extensive invasion of the uvea and sclera by a pleomorphic cell population that formed disorganized cords and exhibited PAS-positive basement membrane material. Necropsy revealed a morphologically similar tumor in the ipsilateral orbit and lung. On immunohistochemical examination, the intraocular tumor stained diffusely immunopositive for vimentin, S-100, and neuron-specific enolase and multifocally, sparsely immunopositive for cytokeratin AE1/AE3. The orbital and thoracic tumors stained positively for vimentin but negatively for cytokeratin AE1/AE3. There are few reports of canine metastatic iridociliary adenocarcinoma in the literature; this is the first with immunohistochemical analysis.

Fulminant abdominal gas gangrene in metastatic colon cancer

PubMed Central

BOZKURT, MUSTAFA; OKUTUR, KEREM; AYDIN, KÜBRA; NAMAL, ESAT; ÖZTÜRK, AKIN; BALCI, CEM; DEMIR, GÖKHAN

2012-01-01

We report a case of fulminant abdominal gas gangrene in a patient with metastatic colon cancer. A 39-year-old patient with descending colon, high-grade adenocarcinoma and coexisting liver and lymph node metastases received two courses of chemotherapy. The patient developed sudden acute abdominal symptoms accompanied by septic shock parameters. The imaging findings on computed tomography were characteristic for abdominal gas gangrene, involving liver metastases, portal vein and lymph nodes with associated pneumoperitoneum. The patient succumbed to the disease within hours following the onset of symptoms. PMID:22740933

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma

PubMed Central

Chung, Yumin; Wi, Young Chan; Kim, Yeseul; Bang, Seong Sik; Yang, Jung-Ho; Jang, Kiseok; Min, Kyueng-Whan; Paik, Seung Sam

2018-01-01

Background Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. Methods Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. Results Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05). Conclusions Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone. PMID:29056035

Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-β against Lymph Node–Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models

PubMed Central

Park, Geon-Tae; Kim, Seung U.; Choi, Kyung-Chul

2017-01-01

Purpose Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-β (IFN-β) (HB1.F3.CD.IFN-β) were employed against lymph node–derived metastatic colorectal adenocarcinoma. Materials and Methods CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-β also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. Results In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620, human lymph node–derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. Conclusion The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer. PMID:27188205

Australian contemporary management of synchronous metastatic colorectal cancer.

PubMed

Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

2018-01-01

This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

Prostate carcinoma mimicking a sphenoid wing meningioma.

PubMed

Bradley, Lucas H; Burton, Matthew; Gokden, Murat; Serletis, Demitre

2015-01-01

We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

ClinicalTrials.gov

2018-04-20

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

[An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

PubMed

Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

2013-08-20

Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma

PubMed Central

Mann, Karen M.; Ward, Jerrold M.; Yew, Christopher Chin Kuan; Kovochich, Anne; Dawson, David W.; Black, Michael A.; Brett, Benjamin T.; Sheetz, Todd E.; Dupuy, Adam J.; Chang, David K.; Biankin, Andrew V.; Waddell, Nicola; Kassahn, Karin S.; Grimmond, Sean M.; Rust, Alistair G.; Adams, David J.; Jenkins, Nancy A.; Copeland, Neal G.

2012-01-01

Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by SB in these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer. We identified point mutations in human pancreatic patient samples for another 11 CCGs, including Acvr2a and Map2k4. Importantly, 10% of the CCGs are involved in chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1, Fbxo11, and Vgll4, are also significantly associated with poor patient survival. SB mutagenesis provides a rich resource of mutations in potential cancer drivers for cross-comparative analyses with ongoing sequencing efforts in human pancreatic adenocarcinoma. PMID:22421440

Adenocarcinoma arising at a colostomy site with inguinal lymph node metastasis: report of a case.

PubMed

Iwamoto, Masayoshi; Kawada, Kenji; Hida, Koya; Hasegawa, Suguru; Sakai, Yoshiharu

2015-02-01

Inguinal lymph node metastasis from adenocarcinoma arising at a colostomy site is extremely rare, and the significance of surgical resection for metastatic inguinal lymph nodes has not been established. An 82-year-old woman who had undergone abdominoperineal resection 27 years earlier was admitted to our hospital complaining of bleeding from a colostomy. Physical examination revealed that a tumor at the colostomy site directly invaded into the peristomal skin, and that a left inguinal lymph node was firm and swollen. Positron emission tomography/computed tomography scan demonstrated accumulation of (18)F-fluorodeoxy glucose into both the colostomy tumor and the left swollen inguinal lymph node, while there was no evidence of metastasis to liver or lungs. She underwent open left hemicolectomy with wide local resection of the colostomy, and dissection of left inguinal lymph nodes. Histological diagnosis was a moderately differentiated adenocarcinoma that directly invaded into the surrounding skin and metastasized to the left inguinal lymph node. The patient has been followed up for >5 years without any sign of recurrence. In general, inguinal lymph node metastasis from colorectal cancers is regarded as a systemic disease with a poor prognosis, and so systemic chemotherapy and radiotherapy, but not surgical lymph node dissection, are recommended. Considering the lymphatic drainage route in the present case, inguinal lymph node metastasis does not represent a systemic disease but rather a sentinel nodal metastasis from adenocarcinoma at a colostomy site. Surgical dissection of metastatic inguinal lymph nodes should be considered to enable a favorable prognosis in the absence of distant metastasis to other organs. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pre- and post- transplantation lung cancer in heart transplant recipients.

PubMed

Pricopi, Ciprian; Rivera, Caroline; Varnous, Shaida; Arame, Alex; Le Pimpec Barthes, Françoise; Riquet, Marc

2015-05-01

Heart transplantation after lung cancer surgery can be questionable because of the high risk of cancer recurrence. We report the results of two patients. The first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart-transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous-cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0 adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1 adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis results were different in both cases, demonstrating the absence of metastatic recurrence. Thus, early stage lung cancer might not be a contraindication to heart transplantation, nor are long delays be necessary before registering on a waiting list. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Endometrioid Adenocarcinoma of Caecum Causing Intussusception

PubMed Central

Verma, Rashmi; Osborn, Sally; Horgan, Kieran

2013-01-01

Malignant transformation of endometriosis is rare and is usually seen in ovarian endometriosis. The colon and rectum are the most common sites for extragonadal endometriosis, and although serosal involvement is commonly seen, mucosal involvement is rare. Malignant transformation of endometriosis is a rare but a well-known complication of endometriosis. We report an unusual presentation of endometrioid adenocarcinoma with lymph node metastasis, arising from endometriosis in the caecal wall and causing ileocaecal intussusception. The patient presented with sudden onset of abdominal pain with features suggestive of acute appendicitis. Diagnostic laparoscopy revealed an ileocaecal intussusception. Conversion to open surgery confirmed a caecal mass causing ileocaecal intussusception, and a radical right hemicolectomy was performed. Histology revealed endometrioid adenocarcinoma arising in a focus of endometriosis in the muscularis propria and involving the mucosa, with one regional metastatic lymph node. PMID:23710407

Coexistent Superscan and Lincoln Sign on Bone Scintigraphy.

PubMed

Kulkarni, Mukta; Soni, Atul; Shetkar, Shubhangi; Amer, Momin; Mulavekar, Amruta; Joshi, Prathamesh

2017-08-01

A 70-year-old man underwent Tc-methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible-Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.

Exome sequencing and digital PCR analyses reveal novel mutated genes related to the metastasis of pancreatic ductal adenocarcinoma.

PubMed

Zhou, Bin; Irwanto, Astrid; Guo, Yun-Miao; Bei, Jin-Xin; Wu, Qiao; Chen, Ge; Zhang, Tai-Ping; Lei, Jin-Jv; Feng, Qi-Sheng; Chen, Li-Zhen; Liu, Jianjun; Zhao, Yu-Pei

2012-08-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers with more than 94% mortality rate mainly due to the widespread metastases. To find out the somatically mutated genes related to the metastasis of PDAC, we analyzed the matched tumor and normal tissue samples from a patient diagnosed with liver metastatic PDAC using intensive exome capture-sequencing analysis (> 170× coverage). Searching for the somatic mutations that drive the clonal expansion of metastasis, we identified 12 genes with higher allele frequencies (AFs) of functional mutations in the metastatic tumor, including known genes KRAS and TP53 for metastasis. Of the 10 candidate genes, 6 (ADRB1, DCLK1, KCNH2, NOP14, SIGLEC1, and ZC3H7A), together with KRAS and TP53, were clustered into a single network (p value = 1 × 10(-22)) that is related to cancer development. Moreover, these candidate genes showed abnormal expression in PDAC tissues and functional impacts on the migration, proliferation, and colony formation abilities of pancreatic cancer cell lines. Furthermore, through digital PCR analysis, we revealed potential genomic mechanisms for the KRAS and TP53 mutations in the metastatic tumor. Taken together, our study shows the possibility for such personalized genomic profiling to provide new biological insight into the metastasis of PDAC.

BRAF Inhibitors for BRAF V600E Mutant Colorectal Cancers: Literature Survey and Case Report

PubMed Central

Can, Mehmet Fatih; Ozerhan, Ismail Hakki; Yagci, Gokhan; Zeybek, Nazif; Kavakli, Kutan; Gurkok, Sedat; Gozubuyuk, Alper; Genc, Onur; Erdem, Gokhan; Ozet, Ahmet; Gerek, Mustafa; Peker, Yusuf

2018-01-01

The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic. The patient was evaluated and FOLFOX + bevacizumab treatment was initiated, which was then continued with vemurafenib. A remarkable response was achieved with vemurafenib treatment in which the drug resistance occurred approximately in the sixth month. Even though the patient benefited majorly from vemurafenib, he died on the 20th month of the diagnosis. The expected overall survival for metastatic V600E mutant colon adenocarcinoma patients is 4.7 months. BRAF inhibitors provide new treatment alternatives for V600E mutant colorectal cancers, with prolonged overall survival. BRAF inhibitors in combination with MEK inhibitors are reported as feasible treatment to overcome BRAF inhibitor drug resistance on which phase studies are still in progress. To conclude, BRAF inhibitors alone or in combination with other drugs provide a chance for curing BRAF V600E mutant colorectal cancer patients. PMID:29850361

A case of alpha-fetoprotein-producing esophageal adenocarcinoma.

PubMed

Chen, Yi-Yu; Hsu, Wen-Hung; Hu, Huang-Ming; Wu, Deng-Chyang; Lin, Wen-Yi

2013-02-01

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma. Copyright © 2012. Published by Elsevier B.V.

“Stealth dissemination” of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma

USDA-ARS?s Scientific Manuscript database

Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal a...

An Atypical Metastasis of Follicular-Type Adenocarcinoma of the Thyroid Gland to Thumb

PubMed Central

Huri, Gazi

2011-01-01

Bone metastasis in the hand is rare. The etiology of metastatic hand cancers is different from other bones. Bronchogenic carcinoma is the most common primary tumor metastasis to hand. In this paper a rare case of thumb metastasis from “follicular-type carcinoma” of the thyroid is presented. PMID:23198224

An unusual case of isolated, serial metastases of gallbladder carcinoma involving the chest wall, axilla, breast and lung parenchyma

PubMed Central

Jeyaraj, Pamela; Sio, Terence T.; Iott, Matthew J.

2013-01-01

In the English literature, only 9 cases of adenocarcinoma of the gallbladder with cutaneous metastasis have been reported so far. One case of multiple cutaneous metastases along with deposits in the breast tissue has been reported. We present a case of incidental metastatic gallbladder carcinoma with no intra-abdominal disease presenting as a series of four isolated cutaneous right chest wall, axillary nodal, breast, and pulmonary metastases following resection and adjuvant chemoradiation for her primary tumor. In spite of the metastatic disease coupled with the aggressive nature of the cancer, this patient reported that her energy level had returned to baseline with a good appetite and a stable weight indicating a good performance status and now is alive at 25 months since diagnosis. Her serially-presented, oligometastatic diseases were well-controlled by concurrent chemoradiotherapy and stereotactic radiation therapy. We report this case study because of its rarity and for the purpose of complementing current literature with an additional example of cutaneous metastasis from adenocarcinoma of the gallbladder. PMID:23772306

Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells

PubMed Central

Loutrari, Heleni; Magkouta, Sophia; Papapetropoulos, Andreas; Roussos, Charis

2011-01-01

Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis. PMID:24212641

Aldosterone mediates metastatic spread of renal cancer via the G protein-coupled estrogen receptor (GPER).

PubMed

Feldman, Ross D; Ding, Qingming; Hussain, Yasin; Limbird, Lee E; Pickering, J Geoffrey; Gros, Robert

2016-06-01

Although aldosterone is a known regulator of renal and cardiovascular function, its role as a regulator of cancer growth and spread has not been widely considered. This study tested the hypothesis that aldosterone regulates cancer cell growth/spread via G protein-coupled estrogen receptor (GPER) activation. In vitro in murine renal cortical adenocarcinoma (RENCA) cells, a widely used murine in vitro model for the study of renal cell adenocarcinoma, aldosterone increased RENCA cell proliferation to a maximum of 125 ± 3% of control at a concentration of 10 nM, an effect blocked by the GPER antagonist G15 or by GPER knockdown using short interfering (sh) RNA techniques. Further, aldosterone increased RENCA cell migration to a maximum of 170 ± 20% of control at a concentration of 100 nM, an effect also blocked by G15 or by GPER down-regulation. In vivo, after orthotopic RENCA cell renal transplantation, pulmonary tumor spread was inhibited by pharmacologic blockade of aldosterone effects with spironolactone (percentage of lung occupied by metastasis: control = 68 ± 13, spironolactone = 26 ± 8, P < 0.05) or inhibition of aldosterone synthesis with a high dietary salt diet (percentage of lung: control = 44 ± 6, high salt = 12 ± 3, P < 0.05), without reducing primary tumor size. Additionally, adrenalectomy significantly reduced the extent of pulmonary tumor spread, whereas aldosterone infusion recovered pulmonary metastatic spread toward baseline levels. Finally, inhibition of GPER either with the GPER antagonist G15 or by GPER knockdown comparably inhibited RENCA cell pulmonary metastatic cancer spread. Taken together, these findings provide strong evidence for aldosterone serving a causal role in renal cell cancer regulation via its GPER receptor; thus, antagonism of GPER represents a potential new target for treatment to reduce metastatic spread.-Feldman, R. D., Ding, Q., Hussain, Y., Limbird, L. E., Pickering, J. G., Gros, R. Aldosterone mediates metastatic spread of renal cancer via the G protein-coupled estrogen receptor (GPER). © FASEB.

Don’t get caught out! A rare case of a calcified urachal remnant mimicking a bladder calculus

PubMed Central

Rodrigues, Jonathan Carl Luis; Gandhi, Sanjay

2013-01-01

Computer tomography through the kidneys, ureters and bladder (CT KUB) is the mainstay investigation of suspected renal tract calculi. However, several pathologies other than renal tract calculi can cause apparent urinary bladder calcification. We describe the case of a 45 year old man who presented with left sided renal colic. Prone CT KUB performed on admission revealed a calcified urachal remnant mimicking a urinary bladder calculus in the dependent portion of the urinary bladder, confirmed by reviewing the multi-planar reformatted images. This is the first reported case in the literature of this phenomenon. We discuss the importance of using multi-planar reformatted images (MPR) and maximum intensity projection images (MIP), as well as careful review of previous imaging, in making the correct diagnosis. We also discuss the differential diagnoses that should be considered when presented with urinary bladder calcification. PMID:23705044

Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients.

PubMed

MacLean, G D; Reddish, M A; Longenecker, B M

1997-01-01

The TRUQUANT BR radioimmunoassay, which uses monoclonal antibody B27.29 to quantitate CA27.29 mucin antigen (MUC-1 gene product) in serum, has recently received Food and Drug Administration approval for predicting recurrent breast cancer in patients with stage II and III disease. The purpose of this study was to determine whether the new radioimmunoassay for serum MUC-1 has prognostic significance for patients with metastatic adenocarcinoma receiving active specific immunotherapy (ASI). Using 40 U/ml as the upper limit of "normal," patients with metastatic breast and ovarian cancer with a preimmunotherapy serum CA27.29 mucin > 40 U/ml (CA27.29 Hi patients) had a poorer survival than CA27.29 Lo patients (< or = 40 U/ml) after ASI. There was no significant correlation between preimmunotherapy CA27.29 serum levels and measurable tumor burden. The preimmunotherapy CA27.29 serum level was a predictor of poor survival of metastatic colorectal and pancreatic cancer patients independent of other prognostic factors. There seemed to be two populations of pancreatic cancer patients, separated at 60 U/ml serum CA27.29 (CA27.29 Hi versus Lo patients). A CA27.29 serum level of 22 U/ml separated patients with CA27.29 Hi vs. Lo colorectal cancer. Patients with CA27.29 Lo colorectal and pancreatic cancer survived longer after ASI compared with patients with CA27.29 Hi colorectal and pancreatic cancer, respectively. We suggest that various CA27.29 serum levels define poor prognosis patients (CA27.29 Hi secretors) versus good prognosis patients (CA27.29 Lo secretors) for different cancer types.

RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells.

PubMed

Tsutsumida, Hideaki; Swanson, Benjamin J; Singh, Pankaj K; Caffrey, Thomas C; Kitajima, Shinichi; Goto, Masamichi; Yonezawa, Suguru; Hollingsworth, Michael A

2006-05-15

MUC1 is a highly glycosylated, type I transmembrane protein expressed by normal ductal epithelial cells of the pancreas, breast, lung, and gastrointestinal tract, and overexpressed in many cases of adenocarcinoma. We down-regulated MUC1 expression by RNA interference and investigated the effects on malignant and metastatic potential of a human pancreatic cancer cell line, S2-013. MUC1-suppressed clones, S2-013.MTII.C1 and S2-013.MTII.C2, were established by targeting a sequence 3,151 bp from the initiation codon and characterized in vitro for proliferation, invasion, and adhesion. We evaluated the effects of MUC1 suppression in vivo on tumor growth and metastatic properties following implantation into the cecum or pancreas of athymic mice. MUC1-suppressed clones showed significantly decreased proliferation in vitro and in vivo. Global gene expression was evaluated by oligonucleotide microarray analysis. Surprisingly, genes predicted to increase doubling times (cyclin B1 and cyclin D3) were overexpressed in MUC1-suppressed clones. There were alterations in expression of several genes that may affect the malignant properties of pancreatic cancer. Adhesion of MUC1-suppressed cells in vitro to type IV collagen and fibronectin was slightly increased, and adhesion was slightly decreased to type I collagen and laminin. Results of implantation to cecum and pancreas showed significant reduction of metastasis to lymph nodes, lung, or peritoneal sites compared with S2-013.gfp-neo control cells. These results support the hypothesis that MUC1 contributes significantly to growth and metastasis, and that down-regulation of MUC1 protein expression decreases the metastatic potential of pancreatic adenocarcinoma.

Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

PubMed

Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

2017-08-16

NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P < 0.05) at 2.5 μM lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

PubMed

Shah, Manish A; Janjigian, Yelena Y; Stoller, Ronald; Shibata, Stephen; Kemeny, Margaret; Krishnamurthi, Smitha; Su, Yungpo Bernard; Ocean, Allyson; Capanu, Marinela; Mehrotra, Bhoomi; Ritch, Paul; Henderson, Charles; Kelsen, David P

2015-11-20

Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.

Choroidal and skin metastases from colorectal cancer.

PubMed

Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

2016-11-21

Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m 2 , twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer.

Endometrial metastasis of colorectal cancer with coincident endometrial adenocarcinoma.

PubMed

Colling, Richard; Lopes, Tito; Das, Nagiindra; Mathew, Joe

2010-11-05

Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125- and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20-, CA125+ and CEA- endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis.

Cloacogenic Adenocarcinoma of the Vulva: A Case Report and Review of the Literature.

PubMed

Tepeoğlu, Merih; Üner, Halit; Haberal, A Nihan; Özen, Özlem; Kuşçu, Esra

2017-02-04

Primary adenocarcinoma of the vulva, unrelated to the native glands of perineum is an extremely rare neoplasm. Despite awareness of this lesion for over 40 years, the origin is not beyond speculation. The most reasonable hypothesis is based on the remnants of cloacal differentiation during early days of life. Here we report the case of a 60-year-old patient with a vulvar mass, who underwent partial vulvectomy and bilateral regional lymph node dissection. The tumor was composed of papillary and complex glandular structures and exhibited diffuse positivity for cytokeratin 20 and polyclonal CEA, CDX2, and focal positivity with cytokeratin 7. Unlike the indolent behavior of this malignant neoplasm according to the literature, we found two metastatic inguinal lymph nodes. She did not receive adjuvant therapy and is still alive, free of disease 38 months after surgery. We present different aspects of vulvar adenocarcinomas with a case report.

Coexistent Ampullary Squamous Cell Carcinoma with Adenocarcinoma of the Pancreatic Duct

PubMed Central

Pathak, Gayatri S.; Deshmukh, Sanjay D.; Yavalkar, Prasanna A.; Ashturkar, Amrut V.

2011-01-01

Primary squamous cell carcinoma (SCC) of ampulla has seldom been reported. However, metastatic SCC to ampulla of Vater is well known. We report a case of primary SCC of ampulla of Vater coexistent with well-differentiated adenocarcinoma of the distal pancreatic duct. A 50-year-old female presented with evidence of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed bulging papilla with ulcero-infiltrative growth at the ampulla of Vater. An initial endoscopic biopsy of the ampullary mass showed a well-differentiated SCC. The patient underwent Whipple's operation. Thorough sampling of the dilated portion of the pancreatic duct showed presence of well-differentiated adenocarcinoma of the distal pancreatic duct. Immunohistochemical study with synaptophysin and chromogranin was done with negative result, ruling out neuroendocrine differentiation. Also, a detailed clinical, endoscopic and radiological examination was carried out, that excluded the presence of primary SCC elsewhere. PMID:22064341

Radioactive iodine therapy: Effect on functioning metastases of adenocarcinoma of the thyroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seidlin, S.M.; Marinelli, L.D.; Oshry, E.

1990-09-01

A case of metastatic adenocarcinoma of the thyroid is reported in which treatment by means of radioactive iodine has been successful. The patient was completely thyroidectomized for malignant adenoma in 1923, with neither thyrotoxicosis then nor hypothyroidism postoperatively; 15 years later there developed classic symptoms of hyperthyroidism and severe pain in the lower back. In October 1939 a pulsating tumor removed from the level of the 12th thoracic vertebra proved to be metastatic thyroid adenocarcinoma (histologically well differentiated, with small follicles and colloid). In the next two years hyperthyroidism increased and roentgenograms revealed new metastases in the lungs, upper partmore » of the right femur, second rib on the left side, left ilium, and skull. Roentgenologic irradiation of the metastases proved ineffectual. In March 1943 a tracer dose of radioactive iodine revealed iodine retention by all the known lesions and no evidence of residual thyroid tissue in the neck. Therapeutic amounts of radioactive iodine were administered orally between May and October 1943. Definite and lasting clinical improvement followed. In April 1944 and March 1945 additional I* was administered with a resultant disappearance of pain, increase in weight, and progressive change in all clinical criteria in the direction of hypothyroidism. Roentgenographic evidence pointed to an arrest if not a regression of the disease. No untoward effects followed this therapy. Radioactive iodine seems to be an effective therapeutic agent in the control of this type of tumor.« less

Coincidence between malignant perivascular epithelioid cell tumor arising in the gastric serosa and lung adenocarcinoma.

PubMed

Yamada, Sohsuke; Nabeshima, Atsunori; Noguchi, Hirotsugu; Nawata, Aya; Nishii, Hisae; Guo, Xin; Wang, Ke-Yong; Hisaoka, Masanori; Nakayama, Toshiyuki

2015-01-28

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor (PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary carcinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease.

Ratio of metastatic lymph nodes to total number of nodes resected is prognostic for survival in esophageal carcinoma.

PubMed

Kelty, Clive J; Kennedy, Catherine W; Falk, Gregory L

2010-09-01

The role of the number of metastatic nodes in esophageal cancer surgery is of interest. We assess predictors of survival after oesophagectomy for esophageal and gastroesophageal junction malignancy. Prospective data of consecutive patients undergoing oesophagectomy and systematic lymphadenectomy between 1991 and 2007. Of 224 patients, 148 patients (66%) had adenocarcinoma, 70 (31%) squamous cell carcinoma, and 6 (2.6%) were other tumor types. Five-year survival was 43% with hospital mortality of 3.5%. Locoregional recurrence occurred in 14%. The total number of affected nodes significantly reduced survival (four or more metastatic nodes). Further analysis of the ratio of nodes affected to the total number resected showed a significant decrease in survival as the percentage of positive nodes increased (p < 0.001). Patients undergoing surgery for esophageal cancer should be staged according to a minimum total number of metastatic lymph nodes and ratios because this more accurately predicts survival than current staging systems.

Diagnosis of metastatic melanoma by fine-needle biopsy: analysis of 2,204 cases.

PubMed

Murali, Rajmohan; Doubrovsky, Anna; Watson, Geoffrey F; McKenzie, Paul R; Lee, C Soon; McLeod, Duncan J; Uren, Roger F; Stretch, Jonathan R; Saw, Robyn P M; Thompson, John F; Scolyer, Richard A

2007-03-01

Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases.

Uterine metastasis of lung adenocarcinoma under molecular target therapy with epidermal growth factor receptor tyrosine kinase inhibitors: A case report and review of the literature.

PubMed

Shibata, Mayu; Shizu, Masato; Watanabe, Kazuko; Takeda, Akihiro

2018-02-01

A 63-year-old woman presented with abnormal vaginal bleeding. Her disease history was significant, and included advanced lung adenocarcinoma with a deletion mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene, which was managed by concurrent chemoradiotherapy, followed by molecular targeted therapy with tyrosine kinase inhibitors (TKIs) for a two-year period. Contrast-enhanced computed tomography showed the enlargement of a previously suspicious myoma node, with peripheral enhancement. Hemorrhagic necrosis was also observed on magnetic resonance imaging. Transabdominal hysterectomy and bilateral salpingo-oophorectomy showed solitary intramyometrial metastatic lung adenocarcinoma with a second-site T790M gatekeeper mutation in exon 20 of the EGFR gene. In conclusion, uterine metastasis from lung adenocarcinoma can present a diagnostic challenge. The possibility of lung cancer metastasis should be considered when a uterine mass increases in size during treatment. Molecular analysis of the EGFR gene to detect mutations could provide useful information for planning the treatment strategy. © 2017 Japan Society of Obstetrics and Gynecology.

Breast metastasis of gastric signet-ring cell carcinoma: a case report and literature review.

PubMed

He, Chun-Lan; Chen, Ping; Xia, Bing-Lan; Xiao, Qin; Cai, Feng-Lin

2015-03-26

Cases of primary gastric adenocarcinoma with metastasis to the breast are extremely rare. Till now, only 38 cases have been reported in PubMed since 1908. We herein reported a race case of gastric adenocarcinoma with metastasis to the right breast. Breast biopsy showed invasive signet-ring cell breast carcinoma in the right breast. She was given a TEC regimen (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 600 mg/m(2) every 3 weeks) for one cycle but showed no objective response. Upper gastrointestinal endoscopy demonstrated an ulcerative mass in the gastric body. Biopsy demonstrated low-grade gastric adenocarcinoma with signet-ring features. In immunohistochemistry, mammary malignant cells were positive for cytokeratin 7, cytokeratin 20, villin, and ErbB2/HER2, but negative for gross cystic disease fluid protein-15, estrogen receptor, and progesterone receptor. The diagnosis of metastatic poorly differentiated signet-ring cell adenocarcinoma of the right breast identical to gastric primary was confirmed finally. Gastric cancer with metastasis to the breast can be diagnosed by clinical history, histological findings, and immunohistochemical markers.

Omentalization of cystic sublumbar lymph node metastases for long-term palliation of tenesmus and dysuria in a dog with anal sac adenocarcinoma.

PubMed

Hoelzler, M G; Bellah, J R; Donofro, M C

2001-12-15

A 13-year-old castrated male Bassett Hound was examined because of a 2-week history of severe constipation and tenesmus. Radiography revealed a large cystic mass in the caudal portion of the abdomen that was compressing the urethra and obstructing the pelvic canal. A small perianal mass was also noticed in the region of the left anal sac. Exploratory surgery was performed, but the mass was deemed unresectable. Instead, the mass was incised, drained, and omentalized in an attempt to establish continuous drainage after surgery. Cytologic evaluation of the perianal mass was consistent with a diagnosis of anal sac adenocarcinoma. Histologic evaluation of the abdominal mass revealed it was a lymph node effaced by adenocarcinoma. Despite the poor prognosis for anal sac adenocarcinoma with metastatic spread to the sublumbar lymph nodes, tenesmus and dysuria in this dog remained palliated until the dog's death 18 months after surgery. Omentalization was successful in providing a continuous method of fluid drainage for this cystopapillary abdominal tumor.

Pancreatic Cancer Genomics 2.0: Profiling Metastases.

PubMed

Collisson, Eric A; Maitra, Anirban

2017-03-13

Pancreatic ductal adenocarcinoma, even when diagnosed early, nearly always metastasizes. Recurrent mutations and genomic instability are early events in the disease. Two recent papers advance our understanding of how the cancer genome evolves as the primary tumor migrates from its origin in the pancreas to colonize distant metastatic sites. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.

PubMed

David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

2014-07-01

Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Rare coexistence of sarcoidosis and lung adenocarcinoma.

PubMed

Kachalia, Amit Girish; Ochieng, Pius; Kachalia, Kinjal; Rahman, Habibur

2014-01-01

An eighty year old African-American female was evaluated for cough, chest pain, asymptomatic anemia and 21 pound weight loss over a six month period. Computerized tomography (CT) revealed a spiculated 2.8 cm right upper lobe lung nodule, other smaller nodules and lymphadenopathy. Gallium scan revealed abnormal uptake of radiotracer in lacrimal, hilar and mediastinal glands. Broncho-alveolar lavage showed CD4/CD8 ratio of 2:1 with 15% lymphocytes. Biopsy of right upper lobe lesion and mediastinoscopic lymph node biopsy showed numerous matured uniform non-caseating granulomatous inflammation, however stains and culture for Acid fast bacilli (AFB)/fungal organisms were negative. Patient improved on oral steroids. Six months later she returned with worsening dyspnea and chest X-ray showed bilateral pleural effusions. Thoracocentesis revealed Thyroid transcription factor 1 (TTF1) positive adenocarcinoma cells and Video assisted thoracic surgery (VATS) procedure revealed numerous pleural, pericardial, diaphragmatic metastasis. Biopsy also was positive for TTF1 adenocarcinoma and positive for Epidermal Growth Factor receptor (EGFR) mutation, however negative for Anaplastic Lymphoma Kinase (ALK). Talc pleurodesis was performed. She was treated with erlotinib while steroid was kept on hold. Initial tumor burden decreased but follow-up PET scan six months later showed progression of tumor with lymphadenopathy. After discussion with patient and family, patient opted for hospice care. Oncocentric theory postulates sarcoidosis as an immunological reaction to dispersal of tumor antigen. Sarcocentric theory postulates that cell-mediated immune abnormalities induced by sarcoidosis in CD4 and CD8 cells is involved in the onset of lung cancer. Thus considerable controversy exists regarding sarcoidosis and malignancy. In our case, TTF1 adenocarcinoma cells from thoracocentesis suggest peripheral nodules in right upper lobe and lingula were likely metastatic, presenting as malignant pleural effusions. However if noncaseating granulomatous inflammation is expected as an immunological reaction to tumor antigen, it is very interesting to observe that initial tissue biopsy of primary right upper lobe mass and mediastinal lymph nodes showed matured uniform non-caseating granulomatous inflammation and no evidence of adenocarcinoma. This being said, it would be highly unlikely for sarcoidosis to progress to lung adenocarcinoma within six months. This adds further controversy to whether granulomatous inflammation is a precursor to future malignancy or whether this elderly African-American female was predisposed to develop granulomatous inflammation in presence of a tumor antigen. One can also speculate whether repeat tissue sampling from right upper lobe mass would have shown granulomatous inflammation or TTF1 adenocarcinoma. While evidence is still lacking regarding association between sarcoidosis and lung adenocarcinoma, it is important for clinicians to exclude metastatic malignancy in patients exhibiting clinical and radiographic findings consistent with sarcoidosis.

Clinical Significance of EML4-ALK Fusion Gene and Association with EGFR and KRAS Gene Mutations in 208 Chinese Patients with Non-Small Cell Lung Cancer

PubMed Central

Wei, Sen; Wang, Jing; Wang, Min; Wang, Yuli; Zhou, Qinghua; Liu, Hongyu; Chen, Jun

2013-01-01

The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P<0.05); never-smokers (42.3% vs 13.9% in smokers; P<0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P<0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites. PMID:23341890

Talimogene Laherparepvec, Capecitabine, and Chemoradiation Before Surgery in Treating Patients With Locally Advanced or Metastatic Rectal Cancer

ClinicalTrials.gov

2018-04-30

Rectal Adenocarcinoma; Stage III Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

Lapatinib in Treating Patients With Recurrent and/or Metastatic Adenoid Cystic Cancer or Other Salivary Gland Cancers

ClinicalTrials.gov

2017-03-06

High-grade Salivary Gland Carcinoma; High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor

Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response

PubMed Central

Biswas, Romi; Gao, Shaojian; Cultraro, Constance M.; Maity, Tapan K.; Venugopalan, Abhilash; Abdullaev, Zied; Shaytan, Alexey K.; Carter, Corey A.; Thomas, Anish; Rajan, Arun; Song, Young; Pitts, Stephanie; Chen, Kevin; Bass, Sara; Boland, Joseph; Hanada, Ken-Ichi; Chen, Jinqiu; Meltzer, Paul S.; Panchenko, Anna R.; Yang, James C.; Pack, Svetlana; Giaccone, Giuseppe; Schrump, David S.; Khan, Javed; Guha, Udayan

2016-01-01

We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. PMID:27900369

A rare presentation of metastasis of prostate adenocarcinoma to the stomach and rectum.

PubMed

Soe, Aye Min; Bordia, Sonal; Xiao, Philip Q; Lopez-Morra, Hernan; Tejada, Juan; Atluri, Sreedevi; Krishnaiah, Mahesh

2014-12-01

Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management.

A Rare Presentation of Metastasis of Prostate Adenocarcinoma to the Stomach and Rectum

PubMed Central

Bordia, Sonal; Xiao, Philip Q; Lopez-Morra, Hernan; Tejada, Juan; Atluri, Sreedevi; Krishnaiah, Mahesh

2014-01-01

Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia. He reported the passing of dark colored stools but denied hematemesis or hematochezia. Colonoscopy revealed circumferential nodularity, and histology demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy showed hypertrophic folds in the gastric fundus, and microscopic examination revealed tumor cells positive for prostate-specific antigen. Bone scanning and computed tomography of the abdomen and pelvis did not show metastasis. It is crucial to distinguish primary gastrointestinal cancer from metastatic lesions, especially in patients with a history of cancer at another site, for appropriate management. PMID:25580360

Electron microscopic demonstration of hormone-producing metastatic carcinoma of the choroid from the bronchus.

PubMed

Amemiya, T; Nomura, S

1975-01-01

Clinical, laboratory and pathological findings of a patient in bronchial carcinoma with choroidal metastasis were presented. X-ray examination of the chest suggested the tumor shadow in the posterior segmental bronchus of the right upper lobe of the lung (r-B2b), while funduscopy and fluorescein angiography revealed the presence of choroidal tumor. ACTH levels in tumor tissues at autopsy and in serum were measured and definitely demonstrated and elevated. Histopathologically, the primary lesion was r-B2b and diagnosed as a mucocellular type of adenocarcinoma. The choroidal lesion was metastatic carcinoma. Electron microscopic examination of the choroidal lesion reembedded for electron microscopy from celloidin-embedded materials for light microscopy could reveal the presence of characteristic cytoplasmic granules referred to as neurosecretory-type granules. It is extremely rare that a hormone-producing metastatic carcinoma of the choroid from the bronchus has been proved.

Cytological diagnosis of metastatic glioblastoma in the pleural effusion of a lung transplant patient.

PubMed

Nauen, David W; Li, Qing Kay

2014-07-01

The extracranial metastasis of glioblastoma is a rare event. We report the case of a patient who developed metastatic glioblastoma in pleural effusion 15 months after lung transplant, with emphasis on differential diagnosis based on cytological material. In our case, tumor cells had pleomorphic nuclei, prominent nucleoli, and fine vesicular chromatin. Some were arranged in a poorly formed pseudo-glandular architecture, mimicking a poorly differentiated adenocarcinoma. The cytological diagnosis of metastatic glioblastoma is difficult and depends critically on clinical history and suspicion, particularly in the transplant setting. Review of the literature indicates that transmission/metastasis of intracranial malignancy occurs rarely following organ transplantation, with some debate on the suitability for transplant of organs from affected donors. Although the situation is uncommon, this report of the cytological findings of extracranial glioblastoma may extend our current knowledge and provide additional differential diagnostic information for this entity. © 2013 Wiley Periodicals, Inc.

Unilateral proptosis as the initial manifestation of malignancy.

PubMed

Rakul Nambiar, K; Ajith, P S; Arjunan, Asha

2017-09-01

Proptosis, a common sign with a broad differential diagnosis, is defined as anterior displacement and protrusion of one or both orbital globes. Patients can present with varying degrees of chronicity, visual loss and associated symptoms. The etiology of acquired unilateral proptosis is diverse, ranging from benign to life-threatening. The causes of unilateral proptosis include traumatic, vascular, endocrine, inflammatory, infective and malignant. Breast carcinoma is the most common metastatic cause of proptosis; however, proptosis has never been reported as the initial manifestation of breast carcinoma. Our patient presented with unilateral proptosis secondary to an intraorbital lesion and histopathology of orbital lesion was suggestive of metastatic breast adenocarcinoma. She was later diagnosed to have primary breast carcinoma. We present this unusual case of a 56-year-old woman who presented with proptosis as the initial manifestation of a metastatic breast malignancy. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

EGFR mutations predict a favorable outcome for malignant pleural effusion of lung adenocarcinoma with Tarceva therapy.

PubMed

Guo, Haisheng; Wan, Yunyan; Tian, Guangyan; Liu, Qinghua; Kang, Yanmeng; Li, Yuye; Yao, Zhouhong; Lin, Dianjie

2012-03-01

The aim of the present study was to evaluate the therapeutic effects and adverse reactions of Tarceva treatment for malignant pleural effusion (MPE) caused by metastatic lung adenocarcinomas. One hundred and twenty-eight patients who failed first-line chemotherapy drug treatment were divided into a mutation and a non-mutation group according to the presence or absence of epidermal growth factor receptor (EGFR) mutations. Each patient received closed drainage combined with simple negative pressure suction after thoracoscopic talc poudrage pleurodesis and oral Tarceva treatment. Short-term and long-term clinical therapeutic effects of Tarceva were evaluated. The EGFR mutation rate in pleural metastatic tissues of lung adenocarcinoma acquired through video-assisted thoracoscopic surgery was higher compared to that in surgical resection specimens, plasma specimens and pleural effusion specimens compared to previously reported results. There were significant statistical differences in the average extubation time (p<0.01), drainage volume of pleural effusion (p<0.05), Karnofsky score and formation of encapsulated pleural effusion 4 weeks after surgery (p<0.05) between these two groups. The number of patients with mild pleural hypertrophy in the mutation group was significantly higher compared to the non-mutation group (p<0.01), while the number of patients with severe pleural hypertrophy was significantly reduced (p<0.05). There was significant statistical discrepancy between these two groups in terms of improvement of peripheral blood carcinoembryonic antigen and tissue polypeptide antigen after 4 weeks of therapy. The complete remission rate and the efficacy rate were higher in the mutation group compared to that in the non-mutation group (p<0.05). There was a longer overall survival time after Tarceva treatment in patients with EGFR mutations than those without EGFR mutation. EGFR mutations predict a favorable outcome for malignant pleural effusion of lung adenocarcinoma with Tarceva therapy. Detection of EGFR mutations may determine the responsiveness of malignant pleural effusion to Tarceva treatment.

Histopathological study using computer database of 10 000 consecutive gastric specimens: (2) malignant lesions

PubMed Central

Terada, Tadashi

2016-01-01

Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens collected in the last 12 years 2002–2013 at his pathology laboratory in a relatively large hospital in Japan. Examination of histological sections was done when appropriate. The gastric specimens were made up of 8579 benign conditions and 1421 malignant lesions. The latter comprised gastric carcinoma in 1342 cases (94.4%), gastrointestinal stromal tumor (GIST) in 34 (2.4%), mucosal-associated lymphoid tissue (MALT) lymphoma in 25 (1.8%), non-Hodgkin's malignant lymphoma in 19 (1.3%), and metastatic carcinoma in 1 case (0.1%). Of the 1342 cases of gastric carcinoma, the histological type was as follows: tubular adenocarcinoma in 755 cases, papillary adenocarcinoma in 176, mucinous adenocarcinoma in 147, signet ring cell carcinoma in 145, poorly differentiated adenocarcinoma in 114, adenosquamous carcinoma in 4, and metastatic small cell carcinoma from the lung in 1. In surgically resected cases, the number of early gastric carcinomas was 258 and of advanced carcinoma, 521 cases. In GIST (n = 34), there were 2 cases of the epithelioid type and 32 of the spindle cell type. The size of GIST ranged from 1–15 cm, with a mean of 5.6 cm. KIT (CD117) was positive in 34/34 cases, CD34 in 31/34, desmin 2/34, and S100 4/34. A genetic analysis was performed in 6 cases of GIST, all of which showed point mutation of KIT and/or PDGFRA genes. In MALT lymphoma (n = 25), centrocyte-like cells and lymphoepithelial lesions were seen in every case. Helicobactor pylori infection was noted in 92%. In non-Hodgkin's lymphoma (n = 19), 17 cases were of diffuse large B-cell lymphoma, and 1 was peripheral T-cell lymphoma, while 1 was NK-cell lymphoma. PMID:25667235

The dynamics of HER2 status in esophageal adenocarcinoma

PubMed Central

Creemers, Aafke; Ebbing, Eva A.; Hooijer, Gerrit K.J.; Stap, Lisanne; Jibodh-Mulder, Rajni A.; Gisbertz, Susanne S.; van Berge Henegouwen, Mark I.; van Montfoort, Maurits L.; Hulshof, Maarten C.C.M.; Krishnadath, Kausilia K.; van Oijen, Martijn G.H.; Bijlsma, Maarten F.; Meijer, Sybren L.; van Laarhoven, Hanneke W.M.

2018-01-01

Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative. PMID:29928485

The dynamics of HER2 status in esophageal adenocarcinoma.

PubMed

Creemers, Aafke; Ebbing, Eva A; Hooijer, Gerrit K J; Stap, Lisanne; Jibodh-Mulder, Rajni A; Gisbertz, Susanne S; van Berge Henegouwen, Mark I; van Montfoort, Maurits L; Hulshof, Maarten C C M; Krishnadath, Kausilia K; van Oijen, Martijn G H; Bijlsma, Maarten F; Meijer, Sybren L; van Laarhoven, Hanneke W M

2018-06-01

Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen ( N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment ( N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% ( n = 3) and 3.3% ( n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% ( n = 2) of the resectable patients and 1.6% ( n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.

ALK-rearranged squamous cell lung carcinoma responding to crizotinib: A missing link in the field of non-small cell lung cancer?

PubMed

Vergne, Florence; Quéré, Gilles; Andrieu-Key, Sophie; Descourt, Renaud; Quintin-Roué, Isabelle; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale; Uguen, Arnaud

2016-01-01

ALK-rearrangements are mainly encountered in lung adenocarcinomas and allow treating patients with anti-ALK targeted therapy. ALK-rearranged squamous cell lung carcinomas are rare tumors that can also respond to anti-ALK-targeted therapy. Nevertheless, ALK screening is not always performed in patients with squamous cell lung carcinomas making the identification and treatment of this molecular tumor subtype challenging. We intend to report a rare case of ALK-rearranged lung squamous cell carcinoma with response to crizotinib therapy. We report clinical, pathological, immunohistochemical and fluorescent in situ hybridization data concerning a patient having an ALK-rearranged squamous cell lung cancer diagnosed in our institution. The patient was a 58-year old woman with a metastatic-stage lung cancer. Histopathological and immunohistochemical analyses were performed on a bronchial biopsy sample and concluded in a non-keratinizing squamous cell lung carcinoma expressing strongly cytokeratin 5/6, p63 and p40, which are classic hallmarks of lung squamous cell carcinomas, but also cytokeratin 7 which is more commonly expressed in lung adenocarcinomas. The tumor did not express thyroid transcription factor-1. ALK rearrangement was searched because of the never-smoker status of the patient and resulted in strong positive fluorescent in situ hybridization test and ALK/p80 immunohistochemistry. The patient responded to crizotinib therapy during 213 days. Our observation points out the interest of considering ALK screening in patients with metastatic lung squamous cell carcinomas, especially in patients lacking a usual heavy-smoker clinical history. The histopathological and immunohistochemical features of this particular tumor highlighting the overlapping criteria between lung adenocarcinomas and rare ALK-rearranged squamous cell lung carcinomas could also be relevant to extend ALK screening to tumors with intermediate phenotypes between squamous cell carcinomas and adenocarcinomas and/or arising in non-smokers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Coincidence between malignant perivascular epithelioid cell tumor arising in the gastric serosa and lung adenocarcinoma

PubMed Central

Yamada, Sohsuke; Nabeshima, Atsunori; Noguchi, Hirotsugu; Nawata, Aya; Nishii, Hisae; Guo, Xin; Wang, Ke-Yong; Hisaoka, Masanori; Nakayama, Toshiyuki

2015-01-01

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor (PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary carcinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease. PMID:25632212

Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma

PubMed Central

Banat, G-Andre; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Wilhelm, Jochen; Weigert, Andreas; Olesch, Catherine; Ebel, Katharina; Stiewe, Thorsten; Grimminger, Friedrich; Seeger, Werner; Fink, Ludger; Savai, Rajkumar

2015-01-01

Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition. PMID:26413839

Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

ClinicalTrials.gov

2017-04-20

Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

EGFR Amplification as a Target in Gastroesophageal Adenocarcinoma: Do Anti-EGFR Therapies Deserve a Second Chance?

PubMed

Strickler, John H

2018-06-01

Anti-EGFR therapies have failed to improve survival for unselected patients with metastatic gastroesophageal cancer, but in a subset of patients, EGFR amplification may predict treatment benefit. Maron and colleagues report the clinical activity of anti-EGFR therapies in a cohort of patients with EGFR -amplified metastatic gastroesophageal cancer and utilize serial blood and tumor tissue collection to identify molecular drivers of treatment sensitivity and resistance. Their insights offer a path to overcome technical limitations associated with EGFR amplification and facilitate molecularly targeted therapeutic strategies. Cancer Discov; 8(6); 679-81. ©2018 AACR See related article by Maron et al., p. 696 . ©2018 American Association for Cancer Research.

ATM protein is deficient in over 40% of lung adenocarcinomas.

PubMed

Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

2016-09-06

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

ATM protein is deficient in over 40% of lung adenocarcinomas

PubMed Central

Villaruz, Liza C.; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F.; Stabile, Laura P.; Siegfried, Jill M.; Conrads, Thomas P.; Smith, Neil R.; O'Connor, Mark J.; Pierce, Andrew J.; Bakkenist, Christopher J.

2016-01-01

Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year. PMID:27259260

Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing

PubMed Central

Koucky, Kathrin; Wein, Axel; Konturek, Peter C.; Albrecht, Heinz; Reulbach, Udo; Männlein, Gudrun; Wolff, Kerstin; Ostermeier, Nicola; Busse, Dagmar; Golcher, Henriette; Schildberg, Claus; Janka, Rolf; Hohenberger, Werner; Hahn, Eckhart G.; Siebler, Jürgen; Neurath, Markus F.; Boxberger, Frank

2011-01-01

Summary Background The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). Material/Methods From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m2) as 1-h infusion followed by 5-FU (2000 mg/m2) combined with FA (500 mg/m2) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). Results Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. Conclusions Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001). PMID:21525806

177Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results.

PubMed

Baum, Richard P; Singh, Aviral; Schuchardt, Christiane; Kulkarni, Harshad R; Klette, Ingo; Wiessalla, Stefan; Osterkamp, Frank; Reineke, Ulrich; Smerling, Christiane

2018-05-01

Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic adenocarcinoma, which is still one of the deadliest cancers, with a very poor prognosis. Eligible patients were offered salvage radiopharmaceutical therapy with the novel NTR1 antagonist 177 Lu-3BP-227. Methods: Six patients with confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment options received 177 Lu-3BP-227 for evaluation of NTR1 expression in vivo. Three patients received treatment activities of 5.1-7.5 GBq. Results: Administration of 177 Lu-3BP-227 was well tolerated by all patients. The kidneys were identified as the dose-limiting organ. The most severe adverse event was reversible grade 2 anemia. One patient achieved a partial response and experienced significant improvement of symptoms and quality of life. This patient survived 13 mo from diagnosis and 11 mo from the start of 177 Lu-3BP-227 therapy. Conclusion: This initial report provides clinical evidence of the feasibility of treatment of ductal pancreatic adenocarcinoma using 177 Lu-3BP-227. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

A phase II study of 5-fluorouracil, leucovorin, adriamycin, and cisplatin (FLAP) for metastatic gastric and gastroesophageal junction adenocarcinoma. A Penn Cancer Clinical Trial Group and Roswell Park Cancer Institute Community Oncology Research Program Trial.

PubMed

Vaughn, D J; Meropol, N J; Holroyde, C; Mintzer, D; Nuamah, I; Armstead, B; Douglass, H O; Haller, D G

1997-06-01

A Phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy (FLAP) in patients with previously untreated advanced gastric and gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients were enrolled to received FLAP in this multi-institutional trial. Response, toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated objective responses, with two complete responses (5%) and 13 partial responses (31%). The median time to disease progression was 17 weeks, and the overall survival duration was 30 weeks. Myelosuppression was significant, requiring dose modifications, but there were no treatment-related deaths. FLAP is an active regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We are presently using this regimen in the neoadjuvant setting in patients with gastric and GE junction cancers.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma.

PubMed

Xie, Yangchun; Huang, Jin; Xiao, Desheng; Zhong, Meizuo

2013-06-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma

PubMed Central

XIE, YANGCHUN; HUANG, JIN; XIAO, DESHENG; ZHONG, MEIZUO

2013-01-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease. PMID:23833669

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

ClinicalTrials.gov

2018-04-27

Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

Prognostic value of the immunocytochemical detection of extramural venous invasion in Dukes' C colorectal adenocarcinomas. A preliminary study.

PubMed Central

Lapertosa, G.; Baracchini, P.; Fulcheri, E.; Tanzi, R.

1989-01-01

In postsurgical staging of colorectal adenocarcinomas, it is sometimes difficult to determine the range of possible venous spread. Distinguishing between the extramural veins (especially when the neoplastic embolus takes up the whole lumen and the endothelium cannot be identified) and the smallest extramural lymph nodes (when they are completely replaced by metastatic carcinoma, leaving the capsule alone) is also difficult. This work proposes a more precise definition of true venous invasion to improve histopathologic staging. Immunohistochemical techniques employing commercial antibodies against Factor VIII RAG, with and without enzymatic digestion, and UEA I lectin for residual endothelium detection, were applied, as well as antibodies against vimentin, desmin, and alpha sm-1 actin to detect wall components. The immunohistochemical evaluation of colorectal adenocarcinomas, in particular by anti-alpha sm-1 actin antibodies, permitted a reliable morphologic distinction of the true venous invasion. This factor proved to be relevant for survival rate prediction. Images Figure 1 Figure 2 PMID:2817085

Recurrent mucinous adenocarcinoma of the ovary presenting as an inguino-labial hernia.

PubMed

Ben-Hur, H; Schachter, M; Mashiah, A; Lifschitz-Mercer, B; Pfeffermann, R

1996-01-01

We report a case of a 65-year-old woman who nine years previously had undergone total abdominal hysterectomy and bilateral salpingoophorectomy for a large ovarian cyst. During surgery the cyst had ruptured and some mucinous material had been spilled intraabdominally. Histopathological studies demonstrated the cyst to be a mucinous adenocarcinoma of low malignant potential. Appendectomy had also been performed due to an enlarged appendix, which proved to be a mucocoele. The patient had been lost to subsequent follow-up. Her current presenting symptom was a giant inguino-labial hernia of 25 cm diameter with two small skin perforations leaking a gelatinous discharge. Subsequent laparotomy and inguinal exploration have disclosed herniated small intestine with an attached metastatic multicystic mucinous adenocarcinoma. This case represents a case of borderline mucinous adeno-carcinoma-pseudomyxoma peritonei recurring in a unique pattern as a huge inguino-labial hernia, and serves to emphasize the possible consequences of spillage of ovarian cyst contents during surgery.

Contralateral breast metastasis from pulmonary adenocarcinoma: two cases report and literature review

PubMed Central

Ji, Fang-Fang; Gao, Peng; Wang, Ji-Gang; Zhao, Jie

2012-01-01

Carcinoma metastatic to breast from extra-mammary malignancy is rare and only accounts for 0.4-1.3% of all breast cancer. Two rare cases of single breast metastasis from pulmonary adenocarcinoma were reported here with a brief review of the pertinent literature. The only complaint of the these two female patients was painless breast mass found recently. Most breast metastasis previously reported are present in the upper outer quadrant, however, in our study, one case was found to be located in the lower inner quadrant and the other in the upper inner quadrant. Tumor cells from breast biopsy were immune-positive for thyroid transcription factor-1. The two patients survived 5 and 8 months, respectively, following the diagnosis of both the primary lung tumor and the breast metastasis. Breast metastasis from lung adenocarcinoma is rare but does exist. The awareness of this possibility may help to differentiate the tumor from primary breast carcinoma. Clinical history and immunohistochemical studies are essential to reach the final diagnosis. PMID:22934141

Breast Cancer Metastases to the Gastrointestinal Tract Presenting with Anemia and Intra-abdominal Bleed.

PubMed

Khan, Idrees; Malik, Rehan; Khan, Amina; Assad, Salman; Zahid, Mehr; Sohail, Muhammad Saad; Yasin, Faizan; Qavi, Ahmed H

2017-07-06

Signet ring adenocarcinoma of the breast with synchronous metastasis to the gastrointestinal (GI) tract is a rare occurrence, typically presenting with abdominal pain, dyspepsia, or GI bleed. We report a case of metastatic breast cancer presenting with a complaint of anemia. A further diagnostic evaluation revealed generalized lymphadenopathy, nodular thickening of the urinary bladder wall, bone lesions, and enlarged pancreas. Biopsies from the lymph nodes, pancreatic biopsy, and bladder nodule all revealed a signet cell carcinoma. An upper and lower GI endoscopy revealed multiple ulcerated gastric mucosal nodules and polypoid folds in the cecum and proximal ascending colon; the biopsies from these lesions were also positive for signet ring cell adenocarcinoma.

Adenocarcinoma of apocrine sweat glands in a mouflon (Ovis musimon).

PubMed

Morandi, Federico; Benazzi, Cinzia; Simoni, Paolo

2005-07-01

A free-living mouflon (Ovis musimon) was presented with a mass on the left shoulder. At necropsy, multifocal, slightly protruding whitish spots were noted on the kidneys, and several lymph nodes were abnormal. Histologically, the mass was composed of epithelial cells arranged in tubular and tubulopapillary structures. The cytoplasm of the epithelial cells had numerous periodic acid-Schiff-positive and diastase-resistant granules. Ultrastructurally, the cytoplasm of the neoplastic cells contained numerous pleomorphic secretory granules and microvilli, which partially covered the luminal surface of the tumor cells. Metastatic foci were present in prescapular and mediastinal lymph nodes and kidneys. On the basis of histological and ultrastructural findings, this tumor was diagnosed as a tubulopapillary adenocarcinoma, arising from apocrine sweat glands of the skin.

Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-03-16

High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Occipital condyle syndrome secondary to bone metastases from rectal cancer.

PubMed

Marruecos, J; Conill, C; Valduvieco, I; Vargas, M; Berenguer, J; Maurel, J

2008-01-01

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.

5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

ClinicalTrials.gov

2018-03-28

Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Cost-effectiveness of precision medicine in the fourth-line treatment of metastatic lung adenocarcinoma: An early decision analytic model of multiplex targeted sequencing.

PubMed

Doble, Brett; John, Thomas; Thomas, David; Fellowes, Andrew; Fox, Stephen; Lorgelly, Paula

2017-05-01

To identify parameters that drive the cost-effectiveness of precision medicine by comparing the use of multiplex targeted sequencing (MTS) to select targeted therapy based on tumour genomic profiles to either no further testing with chemotherapy or no further testing with best supportive care in the fourth-line treatment of metastatic lung adenocarcinoma. A combined decision tree and Markov model to compare costs, life-years, and quality-adjusted life-years over a ten-year time horizon from an Australian healthcare payer perspective. Data sources included the published literature and a population-based molecular cohort study (Cancer 2015). Uncertainty was assessed using deterministic sensitivity analyses and quantified by estimating expected value of perfect/partial perfect information. Uncertainty due to technological/scientific advancement was assessed through a number of plausible future scenario analyses. Point estimate incremental cost-effective ratios indicate that MTS is not cost-effective for selecting fourth-line treatment of metastatic lung adenocarcinoma. Lower mortality rates during testing and for true positive patients, lower health state utility values for progressive disease, and targeted therapy resulting in reductions in inpatient visits, however, all resulted in more favourable cost-effectiveness estimates for MTS. The expected value to decision makers of removing all current decision uncertainty was estimated to be between AUD 5,962,843 and AUD 13,196,451, indicating that additional research to reduce uncertainty may be a worthwhile investment. Plausible future scenarios analyses revealed limited improvements in cost-effectiveness under scenarios of improved test performance, decreased costs of testing/interpretation, and no biopsy costs/adverse events. Reductions in off-label targeted therapy costs, when considered together with the other scenarios did, however, indicate more favourable cost-effectiveness of MTS. As more clinical evidence is generated for MTS, the model developed should be revisited and cost-effectiveness re-estimated under different testing scenarios to further understand the value of precision medicine and its potential impact on the overall health budget. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma metastasis.

PubMed

Gao, Liuwei; Liu, Jun; Zhang, Bin; Zhang, Hua; Wang, Daowei; Zhang, Tiemei; Liu, Yang; Wang, Changli

2014-02-01

The mucin MUC4 is a high molecular weight membrane-bound transmembrane glycoprotein that is frequently detected in invasive and metastatic cancer. The overexpression of MUC4 is associated with increased risks for several types of cancer. However, the functional role of MUC4 is poorly understood in lung adenocarcinoma. Using antisense-MUC4-RNA transfected adenocarcinoma cells, we discovered that the loss of MUC4 expression results in epithelial-mesenchymal transition (EMT). We found morphological alterations and the repression of the epithelial marker E-cadherin in transfected cells. Additionally, the loss of MUC4 caused the upregulation of the mesenchymal marker vimentin compared to control cells. Using a MUC4-knockdown versus control LTEP xenograft mice model (129/sv mice), we also found that EMT happened in lung tissues of MUC4-knockdown-LTEP xenograft mice. Moreover, antisense-MUC4-RNA transfected cells had a significantly increased cellular migration ability in vitro. The loss of MUC4 also occurred in lung adenocarcinoma patients with lymph node metastases. We further investigated MUC4 and found that it plays a critical role in regulating EMT by modulating β-catenin. Taken together, our study reveals a novel role for MUC4 in suppressing EMT and suggests that the assessment of MUC4 may function as a prognostic biomarker and could be a potential therapeutic target for lung adenocarcinoma metastasis.

Putative lung adenocarcinoma with epidermal growth factor receptor mutation presenting as carcinoma of unknown primary site

PubMed Central

Yamasaki, Masahiro; Funaishi, Kunihiko; Saito, Naomi; Sakano, Ayaka; Fujihara, Megumu; Daido, Wakako; Ishiyama, Sayaka; Deguchi, Naoko; Taniwaki, Masaya; Ohashi, Nobuyuki; Hattori, Noboru

2018-01-01

Abstract Rationale: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. Patient concerns and diagnoses: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP. Interventions and outcomes: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression. Lessons: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy. PMID:29443782

Malignant Melanoma Presenting as a Mediastinal Malignant Melanoma Presenting as a Mediastinal Unknown Primary Origin?

PubMed

Pujani, Mukta; Hassan, Mohd Jaseem; Jetley, Sujata; Raina, Prabhat Kumar; Kumar, Mukesh

2017-01-01

The most common site of primary malignant melanoma is the skin, however, virtually any organ system may be involved. Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The mediastinum as the site for malignant melanoma is extremely rare, both as a primary or metastatic lesion. Primary malignant melanoma of mediastinum is very rare with only a handful of reports in the literature. We hereby report a rare case of malignant melanoma of mediastinum in a 31 year old male who was initially misdiagnosed on fine needle aspiration cytology as adenocarcinoma for which he received chemotherapy with clinical deterioration. Even on extensive meticulous search, no primary was discovered.

[Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

PubMed

Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

2016-04-01

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Subjecting appropriate lung adenocarcinoma samples to next-generation sequencing-based molecular testing: challenges and possible solutions.

PubMed

Li, Weihua; Qiu, Tian; Ling, Yun; Gao, Shugeng; Ying, Jianming

2018-05-01

Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than in those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations. Moreover, tumor heterogeneity was assessed by heterogeneity score (HS), which was calculated through multiplying by 2 the mutant allele frequency (MAF) of tumor cells. In TKI-naive samples, intratumor heterogeneity could occur in EGFR, KRAS, HER2, BRAF, and PIK3CA mutant tumors, but the degree was variable. Higher EGFR, but lower BRAF and PIK3CA HS values were observed compared with KRAS HS. In TKI-relapsed samples, analysis of concomitant sensitizing EGFR and T790M MAFs showed that intratumor heterogeneity was common in acquired EGFR T790M mutant tumors. The mutational status between primary and metastatic tumors was usually concordant, but KRAS, HER2, and PIK3CA HS were significantly higher in metastatic tumors than in primary tumors. Additionally, the discordance rate of mutational status in multifocal lung adenocarcinomas diagnosed as equivocal or multiple primary tumors was high. Together, our findings demonstrate that a comprehensive quality assessment is necessary during tissue process to mitigate the challenges of poor tumor cellularity, tumor heterogeneity, and multifocal clonally independent tumors. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Overexpression of regulator of G protein signaling 11 promotes cell migration and associates with advanced stages and aggressiveness of lung adenocarcinoma.

PubMed

Yang, Sheng-Huei; Li, Chien-Feng; Chu, Pei-Yi; Ko, Hsiu-Hsing; Chen, Li-Tzong; Chen, Wan-Wen; Han, Chia-Hung; Lung, Jr-Hau; Shih, Neng-Yao

2016-05-24

Regulator of G protein signaling 11 (RGS11), a member of the R7 subfamily of RGS proteins, is a well-characterized GTPase-accelerating protein that is involved in the heterotrimeric G protein regulation of the amplitude and kinetics of receptor-promoted signaling in retinal bipolar and nerve cells. However, the role of RGS11 in cancer is completely unclear. Using subtractive hybridization analysis, we found that RGS11 was highly expressed in the lymph-node metastatic tissues and bone-metastatic tumors obtained from patients with lung adenocarcinoma. Characterization of the clinicopathological features of 91 patients showed that around 57.1% of the tumor samples displayed RGS11 overexpression that was associated with primary tumor status, nodal metastasis and increased disease stages. Its high expression was an independent predictive factor for poor prognosis of these patients. Cotransfection of guanine nucleotide-binding protein beta-5 (GNB5) markedly increased RGS11 expression. Enhancement or attenuation of RGS11 expression pinpointed its specific role in cell migration, but not in cell invasion and proliferation. Signaling events initiated by the RGS11-GNB5 coexpression activated the c-Raf/ERK/FAK-mediated pathway through upregulation of the Rac1 activity. Consistently, increasing the cell invasiveness of the transfectants by additional cotransfection of the exogenous urokinase-plasminogen activator gene caused a significant promotion in cell invasion in vitro and in vivo, confirming that RGS11 functions in cell migration, but requires additional proteolytic activity for cell and tissue invasion. Collectively, overexpression of RGS11 promotes cell migration, participates in tumor metastasis, and correlates the clinicopathological conditions of patients with lung adenocarcinoma.

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.

PubMed

Petrini, Iacopo; Lencioni, Monica; Vasile, Enrico; Fornaro, Lorenzo; Belluomini, Lorenzo; Pasquini, Giulia; Ginocchi, Laura; Caparello, Chiara; Musettini, Gianna; Vivaldi, Caterina; Caponi, Sara; Ricci, Sergio; Proietti, Agenese; Fontanini, Gabriella; Naccarato, Antonio Giuseppe; Nardini, Vincenzo; Santi, Stefano; Falcone, Alfredo

2018-02-14

The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II-III adenocarcinomas. Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was evaluated in cases with an intermediate (+2) staining. EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p= 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p= 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p= 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p= 0.005). EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.

Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.

PubMed

Li, Jin; Qin, Shukui; Xu, Jianming; Xiong, Jianping; Wu, Changping; Bai, Yuxian; Liu, Wei; Tong, Jiandong; Liu, Yunpeng; Xu, Ruihua; Wang, Zhehai; Wang, Qiong; Ouyang, Xuenong; Yang, Yan; Ba, Yi; Liang, Jun; Lin, Xiaoyan; Luo, Deyun; Zheng, Rongsheng; Wang, Xin; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Guo, Hong; Wu, Jingbo; Xu, Nong; Yang, Jianwei; Zhang, Honggang; Cheng, Ying; Wang, Ningju; Chen, Lei; Fan, Zhining; Sun, Piaoyang; Yu, Hao

2016-05-01

There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. © 2016 by American Society of Clinical Oncology.

Metachronous solitary splenic metastasis arising from early gastric cancer: a case report and literature review.

PubMed

Namikawa, Tsutomu; Kawanishi, Yasuhiro; Fujisawa, Kazune; Munekage, Eri; Munekage, Masaya; Sugase, Takahito; Maeda, Hiromichi; Kitagawa, Hiroyuki; Kumon, Tatsuya; Hiroi, Makoto; Kobayashi, Michiya; Hanazaki, Kazuhiro

2017-08-29

The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.

Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2013-09-27

Adenocarcinoma of the Gastroesophageal Junction; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-09

Colon Adenocarcinoma; ERBB2 Gene Amplification; Rectal Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage III Colon Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

[Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

PubMed

Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

2015-03-01

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

Large mass affecting retroperitoneal great vessels: a rare presentation of a cancer of unknown primary with diagnostic dilemma and challenged surgical intervention.

PubMed

Stakia, Paraskevi; Lagos, Panagiotis; Gourgiotis, Stavros; Tzilalis, Vasilios D; Aloizos, Stavros; Salemis, Nikolaos S

2009-01-01

Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

Gastric tumor from metastasis of breast cancer.

PubMed

Yamamoto, D; Yoshida, H; Sumida, K; Ueyama, Y; Kanematsu, S; Shoji, T; Sueoka, N; Tanaka, K; Tsubota, Y; Kon, M

2010-09-01

Metastatic tumours of the stomach have been reported to result from various types of cancer. Among them, gastric metastasis from breast cancer has been recognised in 0.3-18% patients (1-4). Here, a rare case of metastatic gastric tumour derived from breast carcinoma is reported. Gastric endoscopy confirmed a large, friable mass (approximately 5 cm in diameter) in the upper part of the gastric body. The mass within the stomach was difficult to distinguish from primary gastric cancer, although biopsies of this lesion revealed the characteristics of adenocarcinoma. In addition, immunohistochemistry showed the positive expression of mammaglobin. Taken together, the evidence pointed to metastasis of breast cancer to the stomach. The patient was treated with hormonal therapy (letrozole), and the size of the metastasis in the stomach was markedly reduced. Therefore, a gastric metastasis from breast cancer was diagnosed successfully using immunohistochemistry and unnecessary surgery was avoided. In conclusion, although gastric metastatic tumours derived from breast carcinoma are rare, their accurate pre-operative diagnosis and appropriate systemic treatment is essential.

Metastatic anal sac carcinoma with hypercalcaemia and associated hypertrophic osteopathy in a dog

PubMed Central

Giuliano, A.; Salgüero, R.; Dobson, J.

2015-01-01

A seven-year-old male neutered Irish setter was treated for a metastatic anal sac adenocarcinoma (ASAC) and hypercalcaemia by complete surgical excision of the primary tumour and partial excision of the sublumbar lymph nodes. Further enlargement of the sublumbar lymph nodes was linked to recurrent hypercalcaemia 3 months after surgical treatment. Medical treatment with Toceranib and Clodronate showed modest results in the treatment of the tumour and the hypercalcaemia. Radiotherapy of the sublumbar lymph nodes and later concurrent carboplatin chemotherapy resulted in partial tumour remission with marked reduction in size of the lymph nodes and normalization of the calcaemia. Unfortunately, concurrently with subsequent relapse of the hypercalaemia, the dog developed hypertrophic osteopathy (HO) and lumbar spinal metastasis and the dog was euthanized. To the authors’ knowledge, this is the second case of metastatic apocrine gland carcinoma of the anal sac associated with HO and the first case that describe the development of HO late in the stage of the disease. PMID:26623365

A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis

PubMed Central

Reticker-Flynn, Nathan E.; Braga Malta, David F.; Winslow, Monte M.; Lamar, John M.; Xu, Mary J.; Underhill, Gregory H.; Hynes, Richard O.; Jacks, Tyler E.; Bhatia, Sangeeta N.

2013-01-01

Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified ECM and integrin interactions that could serve as therapeutic targets. PMID:23047680

Value of Ki-67 and computed tomography in the assessment of peripheral lung adenocarcinoma.

PubMed

Chen, Cheng; Zhu, Wei-Dong; Zhang, Xiao-Hui; Zhu, Ye-Han; Huang, Jian-An

2016-01-01

This study was designed to determine whether proliferation antigen Ki-67 and/or a computed tomography (CT) value could be used to evaluate the clinical-pathological features of peripheral lung adenocarcinoma. A total of 116 eligible lung cancer patients were enrolled. Nodule size, lymph node metastasis, differentiation, Ki-67 expression and CT findings were assessed. The relationship between clinic parameters and the CT feature was analysed statistically. The percentage of lesions that had ground-glass opacity or localised air bronchogram was significantly greater in low CT value group (<30, p < 0.05). No significant association was observed between CT value and size in the subgroup with CT value > 0 (p = 0.66). As a proliferative marker of lung cancer, Ki-67 was present in a total of 115 (99.9%) of the 116 evaluable primary lung cancers. There was a statistically significant correlation between the Ki-67 index and CT value (p < 0.05). Compared to CT value, Ki-67 index possessed higher sensitivity to predict the differentiation and lymph node metastasis of peripheral lung adenocarcinoma, adding of CT value would enhance its specificity. Combination of Ki-67 expression and CT value determination was useful for the classification of differentiation and metastatic or proliferative potential of peripheral lung adenocarcinoma.

[Adenocarcinoma of the uterine cervix: particularities in diagnosis and treatment].

PubMed

Vandenbroucke, L; Robert, A-L; Lavoué, V; Foucher, F; Henno, S; Levêque, J

2013-05-01

The adenocarcinoma of the uterine cervix accounts for 10 to 20% of the premalignant and malignant lesions and is different from the cervical intraepithelial neoplasia and invasive squamous cell carcinoma. Recent literature review (from 1985 to 2012) based on the literature available. Adenocarcinoma in situ is an induced HPV lesion (role of HPV 18) of the glandular epithelium: its preferential endocervical situation explains the difficulties in the diagnosis and follow-up after conservative treatment. If the hysterectomy remains the gold standard for treatment, the conservative treatments (resection in sano of the lesions with margins of more than 1cm, meticulous study of the operative specimen, compliance with the follow-up) are possible in the young patients who desire to preserve their fertility. The invasive adenocarcinoma is characterized by a more difficult diagnosis because of its endocervical development, and a prognosis less favorable when compared to squamous cell carcinoma with a greater frequency of the lymphatic node involvement and metastatic diffusion. Its treatment must take into account the particular gravity of the factors of worse prognosis (FIGO stage, tumor size, lymphatic node spreading, adenosquamous histological subtype) in particular in the advanced stages and includes beside the surgery, radiotherapy and chemotherapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Identification of metastatic papillary thyroid carcinoma in FNA specimens using thyroid peroxidase immunohistochemistry.

PubMed

Shield, P W; Crouch, S J; Papadimos, D J; Walsh, M D

2018-06-01

We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma). Thyroid tumours were stained with TTF1 and Tg in addition to TPO. All cases of metastatic lung carcinoma also had TTF-1 staining results. TPO staining was negative in all non-thyroid malignancies. Ninety percent (26/29) of PTC were positive. All positive cases showed strong cytoplasmic staining, although 54% (14/26) showed positivity in less than half of the cells. By comparison, Tg staining of TPC cases was present in 62% and TTF-1 in 100%. In addition to showing higher sensitivity, interpretation of staining results with TPO was generally easier with than Tg. All metastatic lung adenocarcinomas were positive for TTF-1 and TPO negative. The six medullary cancers showed positivity in 17%, 0% and 83% with TPO, Tg and TTF-1, respectively. TPO (mAb EP159) may be a useful addition to immunohistochemical panels for FNA specimens where metastatic PTC is a consideration, particularly in cases where metastatic lung carcinoma features in the differential diagnosis. © 2018 John Wiley & Sons Ltd.

Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

PubMed

Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

2016-06-01

Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the pivotal clinical trial. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

An unusual case of gastric cancer presenting with breast metastasis with pleomorphic microcalcifications.

PubMed

Luk, Yiu Shiobhon; Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai

2012-09-01

Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatment.

Adenocarcinoma metastatic to the uterine cervix: a case series.

PubMed

Pérez-Montiel, Delia; Serrano-Olvera, Alberto; Salazar, Luz Calderón; Cetina-Pérez, Lucely; Candelaria, Myrna; Coronel, Jaime; Montalvo, Luis Alonso Herrera; de León, David Cantú

2012-03-01

The objectives of this report are, first, to describe the clinical behavior of cases of carcinoma metastatic to the uterine cervix treated at our institution in order to carry out a systematic review to establish the behavioral patterns of the most frequent metastases to the cervix and, second, to generate guidelines for their diagnosis and treatment. At the National Institute of Cancer of Mexico (INCan), we performed a review of the clinical files with a diagnosis of malignant neoplasm metastatic to the uterine cervix between 1990 and 2009. For a systematic review, we conducted a PubMed search between the years 1970 and 2009 of case reports and series of cases of patients with metastatic gastric, breast, ovarian and colorectal cancer. We analyzed each report individually and extracted the patients' clinical data from our cases and reports, including the primary tumor, cervical metastases and survival rates. There were 10 cases of tumors metastatic to the uterine cervix. Metastasis was documented in one-half of the patients during follow up, with two of these cases having the cervix as the only site. We included the following reports in the systematic review: 13 reports of gastric-associated cancer, 30 related to breast cancer, nine with ovarian-associated cancer and 10 related to colorectal cancer. Metastatic cervical activity is an infrequent event. The prognosis of survival is poor in the presence of gastric or ovarian cancer and cervical metastases. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer

PubMed Central

Homann, Nils; Pauligk, Claudia; Illerhaus, Gerald; Martens, Uwe M.; Stoehlmacher, Jan; Schmalenberg, Harald; Luley, Kim B.; Prasnikar, Nicole; Egger, Matthias; Probst, Stephan; Messmann, Helmut; Moehler, Markus; Fischbach, Wolfgang; Hartmann, Jörg T.; Mayer, Frank; Höffkes, Heinz-Gert; Koenigsmann, Michael; Arnold, Dirk; Kraus, Thomas W.; Grimm, Kersten; Berkhoff, Stefan; Post, Stefan; Jäger, Elke; Bechstein, Wolf; Ronellenfitsch, Ulrich; Mönig, Stefan; Hofheinz, Ralf D.

2017-01-01

Importance Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie–fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures The primary end point was overall survival. Results In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Conclusions and Relevance Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. Trial Registration clinicaltrials.gov identifier: NCT00849615 PMID:28448662

Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial.

PubMed

Al-Batran, Salah-Eddin; Homann, Nils; Pauligk, Claudia; Illerhaus, Gerald; Martens, Uwe M; Stoehlmacher, Jan; Schmalenberg, Harald; Luley, Kim B; Prasnikar, Nicole; Egger, Matthias; Probst, Stephan; Messmann, Helmut; Moehler, Markus; Fischbach, Wolfgang; Hartmann, Jörg T; Mayer, Frank; Höffkes, Heinz-Gert; Koenigsmann, Michael; Arnold, Dirk; Kraus, Thomas W; Grimm, Kersten; Berkhoff, Stefan; Post, Stefan; Jäger, Elke; Bechstein, Wolf; Ronellenfitsch, Ulrich; Mönig, Stefan; Hofheinz, Ralf D

2017-09-01

Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. The primary end point was overall survival. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. clinicaltrials.gov identifier: NCT00849615.

Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

PubMed

Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

2016-03-01

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

PubMed

Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

2016-01-01

Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Expression of CDX-2 and Ki-67 in different grades of colorectal adenocarcinomas.

PubMed

Sen, Anway; Mitra, Sumit; Das, Ram Narayan; Dasgupta, Shatavisha; Saha, Koushik; Chatterjee, Uttara; Mukherjee, Krishnendu; Datta, Chhanda; Chattopadhyay, Bitan K

2015-01-01

CDX2 is a caudal homeobox gene essential for intestinal differentiation and is specifically expressed in colorectal adenocarcinomas. Its role in colorectal carcinogenesis is not fully elucidated. To study the expression pattern of CDX2 and Ki-67 in different grades of colorectal adenocarcinomas and to observe the relationship of their staining patterns in various tumor stages and to look for correlation if any, between Ki-67 labeling index (Ki-67 LI) and CDX2 expression. A total of 74 cases were enrolled. Detailed clinical profile, peroperative findings, histological grading and staging were noted. Immunohistochemistry for CDX2 and Ki-67 was done, and Ki-67 LI was calculated. CDX2 staining was graded semi-quantitatively, and statistical analysis was done. Age of presentation ranged from 20 to 75 years, and the male:female ratio was 1.83:1. There were 8, 47 and 13 cases of well, moderate and poorly differentiated adenocarcinomas, respectively. The mean Ki-67 LI of well, moderate and poorly differentiated adenocarcinomas were 14.25, 31.34 and 43.08 respectively, and their difference was statistically significant, correlation was also noted with stage. CDX2 expression appeared to be stronger in poorly differentiated cases, but there was no significant difference in its expression in the different grades and stages. There was no correlation between Ki-67 LI and CDX2 immunostaining pattern. The lymph node metastasis showed CDX2 positivity in all the cases. Expression of CDX2 does not significantly change with the grade of colorectal adenocarcinomas. However, it is an important diagnostic marker in metastatic colonic lesions. The Ki-67 LI, on the other hand, showed a strong correlation with histopathological grades.

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Kamran A.; Caudell, Jimmy J.; El-Haddad, Ghassan

Purpose/Objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRTmore » was used for clinical correlation. Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.« less

Gastric cancer and Helicobacter pylori infection in the eastern Libya: a descriptive epidemiological study.

PubMed

Elzouki, Abdel-Naser Y; Buhjab, Soad I; Alkialani, Akram; Habel, Salah; Sasco, Annie J

2012-06-01

The aim of this study was to determine the pattern of histologically-proven gastric cancer in Eastern Libya and explore its association with Helicobacter pylori infection. The registries of the Departments of Histopathology, Faculty of Medicine, Benghazi University and Oncology, Al-Jomhoria Hospital, Benghazi, were reviewed for cases with primary gastrointestinal cancer from January 2000 to December 2002 (sole Histopathology and Oncology Departments in Eastern Libya). Slides of hematoxylin and eosin stain of gastric cancer patients were re-stained to detect H. pylori. The American Joint Committee on Cancer Tumor, Node, Metastasis staging was used for clinical and pathologic staging. Gastric cancer biopsy materials were classified into intestinal or diffuse type according to Lauren criteria. One hundred and fourteen cases of gastric cancer were diagnosed. Tumor stages were: 2 (14%), 3 (21%), 4 (57%) and unknown (8%). Most common site of involvement was the antrum (48%). Diffuse adenocarcinoma occurred in 56 patients (49.1%), intestinal adenocarcinoma in 46 (40.4%) and malignant gastric lymphoma in 12 (10.5%). The overall frequency of H. pylori infection was 63.2% (72/114), more frequent in intestinal adenocarcinoma (71.7%) and malignant lymphoma (66.6%) than diffuse adenocarcinoma (55.3%). The frequency of gastric cancer increased throughout the three years of study. The majority of the patients were diagnosed in locally advanced or metastatic stage. Clearly more efforts need to be given to early detection. We showed a stronger association of H. pylori infection with intestinal type gastric adenocarcinoma and malignant lymphoma than diffuse adenocarcinoma suggesting that H. pylori infection is the most probable causal factor of gastric cancer in this part of Libya. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

High Grade Serous Cystadenocarcinoma of Testis-Case Report of a Rare Ovarian Epithelial Type Tumour

PubMed Central

Nayanar, Sangeetha K; Varadharajaperumal, R; Satheeshbabu, TV; Balasubramanian, Satheesan

2017-01-01

Ovarian epithelial type tumour of testis are extremely rare tumours that resemble ovarian surface epithelial tumours. They usually present as testicular or paratesticular tumours and can be serous, mucinous, endometrioid or Brenner tumour. Serous and mucinous types account for the majority of tumours. The tumours are benign, borderline or malignant, commonly borderline. Here, we report a case of high grade serous cyst adenocarcinoma of testis which manifested as extensive metastasis in supraclavicular, mediastinal and abdominopelvic groups of lymph nodes, lung and adrenal gland without clinical evidence of an overt primary tumour. We report this case so as to make clinicians and pathologists aware of this rare entity and to stress on the fact that this rare entity should be kept in mind when evaluating cases of metastatic adenocarcinoma in male patients. PMID:28764180

Isolated adenocarcinoma of the nipple

PubMed Central

Ahmed, M; Basit, A

2011-01-01

A 47-year-old female presented with a 1-year history of ‘eczematous change’ to the right nipple. Bilateral mammography and ultrasound were entirely normal. Free hand biopsy demonstrated invasive adenocarcinoma of the nipple. The patient underwent a right-sided central segmentectomy and sentinel node biopsy. Histology demonstrated that the nipple was almost completely replaced by an invasive ductal carcinoma with a maximum diameter of 13 mm. Invasion of the underlying breast tissue was to a depth of 3 mm. A single sentinel lymph node demonstrated metastatic carcinoma. Her oestrogen receptor status was positive while HER-2 status was negative. The patient subsequently underwent right-sided axillary node clearance to level three nodes. All 17 nodes in the specimen were found to be within normal limits. She is scheduled to undergo radiotherapy, chemotherapy and hormonal treatment. PMID:22689722

Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

DTIC Science & Technology

1996-09-01

elements of epidermoid carcinoma (A43 1) cells. J. Cell. Biol. 103: 87-94 Winkler, M. (1988). Translational regulation in sea urchin eggs: a complex...and Methods. Error bars show SEM . Figure 2. Rhodamine-actin polymerizes preferentially at the tips of lamellipods in EGF- stimulated cells. MTLn3...lamellipods. B) rhodamine-actin intensity at the cell center. Data for each time point is the average and SEM of 15 different cells. Images A and B

Diagnostic usefulness of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells and reactive mesothelial cells in effusion cell blocks.

PubMed

Cho, Jin Seong; Kim, Ga-Eon; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan

2013-01-01

The aim of our study was to determine the diagnostic value of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells (MAC) and reactive mesothelial cells (RMC) in effusion fluids. A total of 237 cell block specimens from pleural and peritoneal effusions, including 196 malignant effusions with MAC and 41 benign effusions with RMC, were stained with antibodies against MUC1 and MUC4. Membranous staining with or without cytoplasmic staining was considered to be positive. MUC1 immunoreactivity was observed in 194 (99.0%) of 196 cases of MAC and in 20 (48.8%) of 41 cases of RMC. MUC4 immunoreactivity was observed in 174 (88.8%) of 196 cases of MAC and in 4 (9.8%) of 41 cases of RMC. For distinguishing MAC from RMC, the MUC1 reactivity was found to be 99.0% sensitive and 51.2% specific with a positive predictive value of 90.7% and a negative predictive value of 91.3%. The sensitivity of MUC4 for MAC was 88.8%, the specificity was 90.2%, the negative predictive value was 62.7%, and the positive predictive value was 97.8%. Our data suggest that MUC4 appears to be a sensitive and specific marker for differentiating between MAC and RMC. Copyright © 2013 S. Karger AG, Basel.

Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma

PubMed Central

Rohloff, J; Zinke, J; Schoppmeyer, K; Tannapfel, A; Witzigmann, H; Mössner, J; Wittekind, C; Caca, K

2002-01-01

Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients. British Journal of Cancer (2002) 86, 1270–1275. DOI: 10.1038/sj/bjc/6600232 www.bjcancer.com © 2002 Cancer Research UK PMID:11953884

Breast as an unusual site of metastasis- series of 3 cases and review of literature.

PubMed

Hebbar, Ashwin K; Shashidhar, K; S, Krishna Murthy; Kumar, Veerendra; Arjunan, Ravi

2014-09-01

Background and objectives Metastasis to the breast from extra mammary sites is uncommon with an incidence ranging from 1.2 to 2 % in clinical reports. Approximately 300 cases of breast metastasis from extra mammary sites have been reported, mostly in small series or as a single case report. Gastrointestinal adenocarcinoma metastasising to the breast is also very rare and only 30 cases have been reported in the literature. Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological features and immunohistochemistry especially for steroid hormone receptors (ER/PR) and expression of gross cystic disease fluid protein (GCDFP) and presence of other immunohistochemistry protein factors in breast metastasis which are specific to primary site may be helpful in differentiating these two conditions. Materials and methods In this series of 3 cases of breast as an unusual site of metastasis, we present different cases of adenocarcinoma of stomach, sigmoid colon and kidney with metastasis to the breast and discuss the differential diagnosis and management plans. Conclusion In conclusion, secondary tumors to the breast are rare and thus differentiating primary tumors from metastatic breast carcinoma is important for rational and optimum therapy and avoidance of unnecessary radical surgery. Palpable breast lump without typical radiological signs of primary breast carcinoma in patients with known primary should be suspected of representing metastasis.

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

PubMed

Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Sakamoto, Takuya; Akiyama, Yasuki; Kuwahara, Ryuichi; Morimoto, Yoshihiro; Ishida, Tomo; Oneda, Yasuo; Murakami, Kouhei; Naito, Atsushi; Kagawa, Yoshinori; Takeno, Atsushi; Kato, Takeshi; Tamura, Shigeyuki

2016-11-01

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel plus GEM can be the standard treatment for patients with metastatic pancreatic adenocarcinoma.

Primary small-bowel malignancy: update in tumor biology, markers, and management strategies.

PubMed

Shenoy, Santosh

2014-12-01

Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies. Relevant articles from PubMed/Medline and Embase searches were collected using the phrases "small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma". Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma. Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.

[Paget disease of the vulva. 36 cases].

PubMed

Molinie, V; Paniel, B J; Lessana-Leibowitch, M; Moyal-Barracco, M; Pelisse, M; Escande, J P

1993-01-01

Thirty six patients with Paget's disease of the vulva were reviewed. The median age of the patients at diagnosis was 67 years (range: 45-91 years). One patient had a history of previous mammary adenocarcinoma. Screening for malignancy revealed two colonic tumours. Two patients with negative screening at presentation developed, 12 and 18 months respectively after vulvectomy, an ovarian carcinoma stage IIc and a cervical and urethral adenocarcinoma. All patients were treated by surgery based on extent of the disease. The operations performed included total vulvectomy (n = 11), partial vulvectomy (n = 14) and wide local excision (n = 4). Out of the 36 patients, 29 were available to follow-up. The median follow-up period was 74 months (range 2-204 months). Three patients died of metastatic disease due to vulval adenocarcinoma and breast carcinoma, or of liver metastases from an unknown adenocarcinoma. Eighteen of the 29 patients followed up remained free of disease. Five out of the 16 patients with positive margins recurred, as did 5 out of 9 patients with negative margins. Treatment of Paget's disease of the vulva is surgical. In order to prevent recurrence, some authors have proposed surgical excision extending beyond the visible clinical lesions with intraoperative frozen sections. The data we recorded show that free margins do not seem to correlate with recurrence, so that large excision beyond the clinical lesion is not useful.

Screening and identification of gastric adenocarcinoma metastasis-related genes by using cDNA microarray coupled to FDD-PCR.

PubMed

Wang, Jian-Hua; Chen, Shi-Shu

2002-07-01

To clone gastric adenocarcinoma metastasis related genes, RF-1 cell line (primary tumor of a gastric adenocarcinoma patient ) and RF-48 cell line (its metastatic counterpart) were used as a model for studying the molecular mechanism of tumor metastasis. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from RF-1 and RF-48 mRNA samples by reverse transcription method. The two color probes were then mixed and hybridized to the cDNA chip constructed by double-dots of 4 096 human genes, and scanned at two wavelengths. The experiment was repeated for 2 times. Differential expression genes from the above two cells were analyzed using the computer. 138 in all genes (3.4%) revealed differential expression in RF-48 cells compared with RF-1 cells: 81(2.1%) genes revealed apparent up-regulation, and 56(1.3%) genes revealed down-regulation. 45 genes involved in gastric adenocarcinoma metastasis were cloned using fluorescent differential display-PCR (FDD-PCR), including 3 novel genes. There were 7 differential expression genes that agreed with each other in two detection methods. The possible roles of some differential expressed genes, which maybe involved in the mechanism of tumor metastasis, were discussed. cDNA chip was used to analyze gene expression in a high-throughput and large scale manner, in combination with FDD-PCR for cloning unknown novel genes. In conclusion, some genes related to metastasis were preliminarily scanned, which would contribute to disclose the molecular mechanism of gastric adenocarcinoma metastasis.

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

PubMed

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.

PubMed

Weyemi, Urbain; Redon, Christophe E; Choudhuri, Rohini; Aziz, Towqir; Maeda, Daisuke; Boufraqech, Myriem; Parekh, Palak R; Sethi, Taresh K; Kasoji, Manjula; Abrams, Natalie; Merchant, Anand; Rajapakse, Vinodh N; Bonner, William M

2016-02-15

The epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induces mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reverses these changes, as does silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibit a similar metastatic behaviour, but the cells with re-expressed H2A.X are substantially more metastatic. We surmise that H2A.X re-expression leads to partial EMT reversal and increases robustness in the HCT116 cells, permitting them to both form tumours and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlate inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a regulator of EMT.

68Ga-PSMA PET/CT in prostate cancer.

PubMed

García Garzón, J R; de Arcocha Torres, M; Delgado-Bolton, R; Ceci, F; Alvarez Ruiz, S; Orcajo Rincón, J; Caresia Aróztegui, A P; García Velloso, M J; García Vicente, A M

Positron emission tomography/computed tomography (PET/CT) with 68 Ga-PSMA is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen (PSMA) expression. PSMA is a transmembrane protein present in all prostatic tissues. Increased PSMA expression is seen in several malignancies, although prostate cancer is the tumour where it presents higher concentrations. Almost all prostate adenocarcinomas show PSMA expression in most of lesions, primary and metastatic. Immunohistochemistry has demonstrated that the expression of PSMA increases in patients with de-differentiated, metastatic or hormone-refractory tumours. Moreover, the expression level of PSMA has a prognostic value for disease outcome. PET measures the three-dimensional distribution of 68 Ga-PSMA, producing semi-quantitative images that allow for non-invasive assessment of PSMA expression. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Discovery and validation of vascular endothelial growth factor (VEGF) pathway polymorphisms in esophageal adenocarcinoma outcome.

PubMed

Eng, Lawson; Azad, Abul Kalam; Qiu, Xin; Kong, Qin Quinn; Cheng, Dangxiao; Ying, Nanjiao; Tse, Alvina; Kuang, Qin; Dodbiba, Lorin; Renouf, Daniel J; Marsh, Sharon; Savas, Sevtap; Mackay, Helen J; Knox, Jennifer J; Darling, Gail E; Wong, Rebecca K S; Xu, Wei; Liu, Geoffrey; Faluyi, Olusola O

2015-09-01

Polymorphisms in the vascular endothelial growth factor (VEGF)/angiogenesis pathway have been implicated previously in cancer risk, prognosis and response to therapy including in esophageal adenocarcinoma. Prior esophageal adenocarcinoma studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new VEGF pathway polymorphisms associated with esophageal adenocarcinoma prognosis and validated them in an independent cohort of esophageal adenocarcinoma patients. In 231 esophageal adenocarcinoma patients of all stages/treatment plans, 58 genetic polymorphisms (18 KDR, 7 VEGFA and 33 FLT1) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then validated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median OS and PFS were 20 and 12 months, respectively. KDR rs17709898 was found significantly associated with PFS (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). FLT1 rs3794405 and rs678714 were significantly associated with OS (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No VEGFA polymorphisms were found significantly associated with either outcome. Upon validation, FLT1 rs3794405 remained strongly associated with OS (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). FLT1 rs3794405 is significantly associated with OS in esophageal adenocarcinoma, whereby each variant allele confers a 45-60% increased risk of mortality. Validation and evaluation of this association in other cancer sites are warranted. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

E-Cadherin as a Chemotherapy Resistance Mechanism on Metastatic Breast Cancer

DTIC Science & Technology

2011-01-01

Gold Kit (Zymo, San Diego, CA) per the manufacturer’s specifications. MSP was performed in the way of Corn et al [62] or using the CpG WIZ E-cadherin...Amplification Kit per the manufacturer’s instructions (Millipore, Temecula, CA). Briefly, in the method of Corn , a nested PCR method was used, in...cadherin gene promoter methylation in prostatic adenocarcinomas. Cancer 92(11): 2786-95. 29. Corn , PG, BD Smith, ES Ruckdeschel et al (2000) E-cadherin

Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret

USGS Publications Warehouse

Carpenter, J.W.; Davidson, J.P.; Novilla, M.N.; Huang, J.C.M.

1980-01-01

A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret.

PubMed

Carpenter, J W; Davidson, J P; Novilla, M N; Huang, J C

1980-10-01

A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

Radical cystectomy at Roswell Park Memorial Institute. Preoperative and post operative observations.

PubMed

Eisenkraft, S; Pontes, J E

1984-01-01

Between January 1979 and March 1983, 63 consecutive patients underwent cystectomy and urinary diversion for primary carcinoma of the bladder at Roswell Park Memorial Institute (RPMI). Fifty-five patients had transitional cell carcinoma, 6 squamous cell carcinoma and 2 adenocarcinoma of the bladder. Twelve patients with bladder cancer were found to have adenocarcinoma of the prostate on the pathological specimen. Preoperative radiation was given to 41 patients. Thirty-six patients received 4000 rads preoperatively followed by radical cystectomy, 5 patients received 2000 rads. Thirteen patients received 6000 rads as curative treatment and underwent salvage cystectomy and colon conduit because of failure. There was no operative mortality. Severe complications in the early postoperative period occurred in 19 instances, some patients having more than one complication. Late complications necessitating surgical correction occurred in 5 patients. Although radical cystectomy is effective in controlling the local disease, most patients still died of metastatic transitional cell carcinoma.

Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma.

PubMed

Ludmir, Ethan B; McCall, Shannon J; Czito, Brian G; Palta, Manisha

2014-09-19

An 82-year-old man presented with progressive right frontal headaches. The patient's history was significant for benign polyps on surveillance colonoscopy 2 years prior, without high-grade dysplasia or carcinoma. MRI revealed an enhancing lesion arising within the superomedial aspect of the right orbit. Lesion biopsy demonstrated histological appearance and immunophenotype suggestive of colonic adenocarcinoma. Staging positron emission tomography/CT showed visceral metastases and diffuse activity in the posterior rectosigmoid, consistent with metastatic colon cancer. Treatment of the orbital lesion with external beam radiotherapy to 30 Gy resulted in significant palliation of the patient's headaches. The patient expired 2 months following treatment completion due to disease progression. Orbital metastasis as the initial presentation of an occult colorectal primary lesion is exceedingly rare, and occurred in this patient despite surveillance colonoscopy. Radiotherapy remains an efficacious modality for treatment of orbital metastases. 2014 BMJ Publishing Group Ltd.

Expression of PDGFR-β and Kit in canine anal sac apocrine gland adenocarcinoma using tissue immunohistochemistry.

PubMed

Brown, R J; Newman, S J; Durtschi, D C; Leblanc, A K

2012-03-01

Canine anal sac apocrine gland adenocarcinoma (ASAGAC) is an uncommon but highly invasive and metastatic malignancy. Toceranib phosphate (Palladia) is a receptor tyrosine kinase (RTK) inhibitor that targets several members of the split kinase RTK family. These membrane receptors are important for cell cycling, apoptosis and angiogenesis, all of which can contribute to carcinogenesis. The objective of this study was to evaluate archived, paraffin-embedded canine ASAGAC and normal canine anal sacs for immunohistochemical detection of Kit and platelet-derived growth factor receptor beta (PDGFR-β). Two of 77 neoplasms (2.6%) expressed Kit. Fifteen of the neoplasms (19.5%) were positive for PDGFR-β expression. None of the normal canine anal sac epithelium expressed Kit or PDGFR-β. Because of these results, further investigation should be considered to determine the role of RTKs in the clinical course and treatment of canine ASAGAC. © 2011 Blackwell Publishing Ltd.

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

PubMed Central

Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina

2015-01-01

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential. PMID:26522614

Iris metastasis of gastric adenocarcinoma.

PubMed

Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, U Emrah; Cosar, C Banu; Ozkiris, Abdullah

2016-03-08

Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis. A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy. Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

PubMed

Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina

2015-11-02

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

Recent advances in immunohistochemistry in the diagnosis of ovarian neoplasms

PubMed Central

McCluggage, W

2000-01-01

This leader reviews recent advances in immunohistochemistry that are useful in the diagnosis of ovarian neoplasms. These include the value of different anticytokeratin antibodies in the distinction between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. The value of antibodies against so called tumour specific antigens, such as CA125 and HAM56, in determining the ovarian origin of an adenocarcinoma is also reviewed. In recent years, several studies have investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours and in the distinction between these neoplasms and their histological mimics. These antibodies include those directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like factor, melan A, and calretinin. Of these, anti-α inhibin appears to be of most diagnostic value. It is stressed that these antibodies should always be used as part of a larger panel and not in isolation.J Clin Pathol(J Clin Pathol 2000;53:327–334) Key Words: ovarian neoplasms • diagnosis • immunohistochemistry PMID:10889812

Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma

PubMed Central

Eivaz-Mohammadi, Sahar; Tarar, Omer; Malik, Khurram; Syed, Amer K.

2014-01-01

A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma. PMID:25349615

HOXB2 as a novel prognostic indicator for stage I lung adenocarcinomas.

PubMed

Inamura, Kentauro; Togashi, Yuki; Okui, Michiyo; Ninomiya, Hironori; Hiramatsu, Miyako; Satoh, Yukitoshi; Okumura, Sakae; Nakagawa, Ken; Shimoji, Takashi; Noda, Tetsuo; Ishikawa, Yuichi

2007-09-01

Outcomes of patients with lung adenocarcinomas can be predicted to some extent from the pathologic stage (p-stage). Although all attempts are made to fully remove cancer lesions, still a number of p-stage I patients without metastatic disease at the time of surgery develop recurrences and die of cancer. It is thus very important to identify p-stage I patients who are at risk of recurrence. Previously, using microdissected samples, we identified metastasis-related genes. Using real-time reverse-transcriptase polymerase chain reaction analysis, we investigated the transcriptional levels of the top metastasis-related genes using 96 independent test lung adenocarcinoma samples and investigated their correlations with the prognosis. We document evidence that p-stage I patients with HOXB2 up-regulation have a worse prognosis than those with HOXB2 down-regulation (p = 0.0065), whereas the HOXB2 status has no prognostic significance for p-stage II-IV patients. Comparing tumors and corresponding normal lung tissue, we confirmed HOXB2 up-regulated lesions to have much higher HOXB2 expression than the corresponding normal tissue. Confirmation with a larger number of samples is needed, with further research to clarify the molecular functions of HOXB2.

Adenocarcinoma of the third duodenal portion: Case report and review of literature

PubMed Central

Sista, Federico; Santis, Giuseppe De; Giuliani, Antonio; Cecilia, Emanuela Marina; Piccione, Federica; Lancione, Laura; Leardi, Sergio; Amicucci, Gianfranco

2012-01-01

We focus on the diagnostic and therapeutic problems of duodenal adenocarcinoma, reporting a case and reviewing the literature. A 65-year old man with adenocarcinoma in the third duodenal portion was successfully treated with a segmental resection of the third part of the duodenum, avoiding a duodeno-cephalo-pancreatectomy. This tumor is very rare and frequently affects the III and IV duodenal portion. A precocious diagnosis and the exact localization of this neoplasia are crucial factors in order to decide the surgical strategy. Given a non-specificity of symptoms, endoscopy with biopsy is the diagnostic gold standard. Duodeno-cephalo-pancreatectomy (DCP) and segmental resection of the duodenum (SRD) are the two surgical options, with overlapping morbidity (27% vs 18%) and post operative mortality (3% vs 1%). The average incidence of postoperative long-term survival is 100%, 73.3% and 31.6% of cases after 1, 3 and 5 years from surgery, respectively. Long-term survival is made worse by two factors: the presence of metastatic lymph nodes and tumor localization in the proximal duodenum. The two surgical options are radical: DCP should be used only for proximal localizations while SRD should be chosen for distal localizations. PMID:22347539

Barrett’s oesophagus: Current controversies

PubMed Central

Amadi, Chidi; Gatenby, Piers

2017-01-01

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett’s oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett’s oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett’s segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett’s segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus. PMID:28811703

Barrett's oesophagus: Current controversies.

PubMed

Amadi, Chidi; Gatenby, Piers

2017-07-28

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.

Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

PubMed

Xu, Jian-Ping; Liu, Xiao-Yan; Yang, Sheng; Zhang, Chang-Gong; Wang, Lin; Shi, Yuan-Kai

2016-07-01

To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute-Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

ClinicalTrials.gov

2017-07-10

Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.

PubMed

Shah, Manish A; Jhawer, Minaxi; Ilson, David H; Lefkowitz, Robert A; Robinson, Edric; Capanu, Marinela; Kelsen, David P

2011-03-01

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.

Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.

PubMed

Shah, Manish A; Ramanathan, Ramesh K; Ilson, David H; Levnor, Alissa; D'Adamo, David; O'Reilly, Eileen; Tse, Archie; Trocola, Robin; Schwartz, Lawrence; Capanu, Marinela; Schwartz, Gary K; Kelsen, David P

2006-11-20

Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma

PubMed Central

Shah, Manish A.; Jhawer, Minaxi; Ilson, David H.; Lefkowitz, Robert A.; Robinson, Edric; Capanu, Marinela; Kelsen, David P.

2011-01-01

Purpose To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Patients and Methods Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2, leucovorin 400 mg/m2 on day 1, fluorouracil 1,000 mg/m2/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. Results In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). Conclusion mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively. PMID:21189380

Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

PubMed

Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

2014-03-01

Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome furthers our understanding of malignant mesothelioma, identified galectin 1 as a potential diagnostic biomarker, and highlighted several possible prognostic biomarkers of this disease.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

PubMed

Janjigian, Y Y; Werner, D; Pauligk, C; Steinmetz, K; Kelsen, D P; Jäger, E; Altmannsberger, H-M; Robinson, E; Tafe, L J; Tang, L H; Shah, M A; Al-Batran, S-E

2012-10-01

To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.

An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast.

PubMed

Balakrishnan, Bathmapriya; Shaik, Sufiya; Burman-Solovyeva, Irina

2016-01-01

Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT) of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract.

PubMed

Tot, T

2000-06-01

Metastatic signet ring cell carcinomas of unknown primary site can represent a clinical problem. Gastrointestinal signet ring cell carcinomas and invasive lobular carcinomas of the breast are the most common sources of these metastases. Immunohistochemical algorithms have been successfully used in the search for the unknown primary adenocarcinomas. In the present study a series of primary invasive lobular breast carcinomas (79 cases) and their metastases and a series of gastrointestinal signet ring cell carcinomas (22 primary and 13 metastases) were stained with monoclonal antibodies for cytokeratin (CK) 20 and CK7 and for estrogen receptors (ER). The staining was evaluated as negative (no staining), focally (less than 10% of the tumor cells stained) or diffusely positive. All the primary and metastatic gastrointestinal signet ring cell carcinomas proved to be CK20 positive, while only 2/79 (3%) of the primary and 1/21 metastatic lobular carcinomas (5%) stained positively for this CK. None of the gastrointestinal carcinomas and the majority of the lobular carcinomas expressed ER. The majority of the tumors were CK7+. Using CK20 alone, 33 of 34 metastases could be properly classified as gastrointestinal (CK20+) or mammary (CK20-). ER identified 31/34 of breast cancer metastases. By combining the results of CK20 and ER staining all the metastases could be properly classified as the CK20+/ER- pattern identified all the gastrointestinal tumors.

Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer.

PubMed

Le, Dung T; Wang-Gillam, Andrea; Picozzi, Vincent; Greten, Tim F; Crocenzi, Todd; Springett, Gregory; Morse, Michael; Zeh, Herbert; Cohen, Deirdre; Fine, Robert L; Onners, Beth; Uram, Jennifer N; Laheru, Daniel A; Lutz, Eric R; Solt, Sara; Murphy, Aimee Luck; Skoble, Justin; Lemmens, Ed; Grous, John; Dubensky, Thomas; Brockstedt, Dirk G; Jaffee, Elizabeth M

2015-04-20

GVAX pancreas, granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes-expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received ≥ two regimens for metastatic disease. Mean number of doses (± standard deviation) administered in arms A and B were 5.5 ± 4.5 and 3.7 ± 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity. © 2015 by American Society of Clinical Oncology.

Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes–Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer

PubMed Central

Le, Dung T.; Wang-Gillam, Andrea; Picozzi, Vincent; Greten, Tim F.; Crocenzi, Todd; Springett, Gregory; Morse, Michael; Zeh, Herbert; Cohen, Deirdre; Fine, Robert L.; Onners, Beth; Uram, Jennifer N.; Laheru, Daniel A.; Lutz, Eric R.; Solt, Sara; Murphy, Aimee Luck; Skoble, Justin; Lemmens, Ed; Grous, John; Dubensky, Thomas; Brockstedt, Dirk G.; Jaffee, Elizabeth M.

2015-01-01

Purpose GVAX pancreas, granulocyte-macrophage colony-stimulating factor–secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes–expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. Patients and Methods Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. Results A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received ≥ two regimens for metastatic disease. Mean number of doses (± standard deviation) administered in arms A and B were 5.5 ± 4.5 and 3.7 ± 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. Conclusion Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity. PMID:25584002

Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells*

PubMed Central

Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A.; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E.; Sipos, Bence; Baba, Hideo A.; Sitek, Barbara

2016-01-01

Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. PMID:26644413

Immunohistochemical Markers Distinguishing Cholangiocellular Carcinoma (CCC) from Pancreatic Ductal Adenocarcinoma (PDAC) Discovered by Proteomic Analysis of Microdissected Cells.

PubMed

Padden, Juliet; Ahrens, Maike; Kälsch, Julia; Bertram, Stefanie; Megger, Dominik A; Bracht, Thilo; Eisenacher, Martin; Kocabayoglu, Peri; Meyer, Helmut E; Sipos, Bence; Baba, Hideo A; Sitek, Barbara

2016-03-01

Cholangiocellular carcinoma (CCC) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types that arise from epithelial cells of the pancreatobiliary system. Owing to their histological and morphological similarity, differential diagnosis between CCC and metastasis of PDAC located in the liver frequently proves an unsolvable issue for pathologists. The detection of biomarkers with high specificity and sensitivity for the differentiation of these tumor types would therefore be a valuable tool. Here, we address this problem by comparing microdissected CCC and PDAC tumor cells from nine and eleven cancer patients, respectively, in a label-free proteomics approach. The novel biomarker candidates were subsequently verified by immunohistochemical staining of 73 CCC, 78 primary, and 18 metastatic PDAC tissue sections. In the proteome analysis, we found 180 proteins with a significantly differential expression between CCC and PDAC cells (p value < 0.05, absolute fold change > 2). Nine candidate proteins were chosen for an immunohistochemical verification out of which three showed very promising results. These were the annexins ANXA1, ANXA10, and ANXA13. For the correct classification of PDAC, ANXA1 showed a sensitivity of 84% and a specificity of 85% and ANXA10 a sensitivity of 90% at a specificity of 66%. ANXA13 was higher abundant in CCC. It presented a sensitivity of 84% at a specificity of 55%. In metastatic PDAC tissue ANXA1 and ANXA10 showed similar staining behavior as in the primary PDAC tumors (13/18 and 17/18 positive, respectively). ANXA13, however, presented positive staining in eight out of eighteen secondary PDAC tumors and was therefore not suitable for the differentiation of these from CCC. We conclude that ANXA1 and ANXA10 are promising biomarker candidates with high diagnostic values for the differential diagnosis of intrahepatic CCC and metastatic liver tumors deriving from PDAC. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Microwave ablation for treatment of hepatic neoplasia in five dogs.

PubMed

Yang, Toni; Case, J Brad; Boston, Sarah; Dark, Michael J; Toskich, Beau

2017-01-01

CASE DESCRIPTION 5 dogs between 9 and 11 years of age were evaluated for treatment of primary (n = 2) or metastatic (3) hepatic neoplasia. CLINICAL FINDINGS Patients were evaluated on an elective (n = 3) or emergency (2) basis. Two dogs with primary hepatic neoplasia were evaluated because of lethargy and inappetence. One dog was referred after an enlarged anal sac was detected via palpation per rectum during a routine physical examination. Two dogs were evaluated on an emergency basis because of lethargy and weakness, and hemoabdomen in the absence of a history of trauma was detected. All 5 dogs underwent thoracic radiography and abdominal ultrasonography, with CT performed in both dogs with primary hepatic neoplasia. All dogs had preoperative evidence of abdominal neoplasia, and none had evidence of thoracic metastasis. TREATMENT AND OUTCOME All dogs underwent ventral midline laparotomy and had diffuse hepatic neoplasia that precluded complete resection. Locoregional treatment with MWA was applied to hepatic lesions (0.5 to 2.5 cm diameter) without procedural complications. Histopathologic diagnoses were biliary adenocarcinoma (n = 1), hemangiosarcoma (2), hepatocellular carcinoma (1), and apocrine gland adenocarcinoma (1). CLINICAL RELEVANCE MWA is being increasingly used as an adjunct in the surgical treatment of human patients with primary and metastatic liver disease. Results of the present small case series suggested that MWA is feasible and potentially effective as an adjunctive treatment for appropriately selected dogs with nonresectable hepatic tumors. Further investigation is indicated.

Malignant tumors associated with ovarian mature teratoma: A single institution experience.

PubMed

Trabzonlu, Levent; Durmaz, Guray; Vural, Cigdem; Muezzinoglu, Bahar; Corakci, Aydin

2017-05-01

The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach. Copyright © 2017 Elsevier GmbH. All rights reserved.

Management of unresectable, locally advanced pancreatic adenocarcinoma.

PubMed

Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

2018-02-01

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

Screening and identification of gastric adenocarcinoma metastasis-related genes using cDNA microarray coupled to FDD-PCR.

PubMed

Wang, Jianhua; Chen, Shishu

2002-10-01

To identify certain gastric adenocarcinoma metastasis-related genes, an RF-1 cell line (primary tumor from a gastric adenocarcinoma patient) and an RF-48 cell line (its metastatic counterpart) were used as a model for studying the molecular mechanism of tumor metastasis. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from RF-1 and RF-48 mRNA samples by the reverse transcription method. The two color probes were then mixed and hybridized to a cDNA chip constructed with double-dots from 4,096 human genes, and scanned at two wavelengths. The experiment was repeated twice. Differentially expressedn genes from the above two cells were analyzed by use of computer. Of the total genes, 138 (3.4%) revealed differential expression in RF-48 cells compared with RF-1 cells: 81 (2.1%) genes revealed apparent up-regulation, and 56 (1.3%) genes revealed down-regulation. Forty-five genes involved in gastric adenocarcinoma metastasis were cloned using fluorescent differential display-PCR (FDD-PCR), including three novel genes. There were seven differentially expressed genes that presented the same behaviour under both detection methods. The possible roles of some differentially expressed genes, which may be involved in the mechanism of tumor metastasis, were discussed. cDNA chip was used to analyze gene expression in a high-throughput and large-scale manner in combination with FDD-PCR for cloning unknown novel genes. Some genes related to metastasis were preliminarily scanned, which would contribute to disclose the molecular mechanism of gastric adenocarcinoma metastasis and provide new targets for therapeutic intervention.

Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

PubMed

Rosenberg, Emily; Buchtel, Lindsey

2016-01-01

A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

Acquired Resistance to Crizotinib from a Mutation in CD74–ROS1

PubMed Central

Awad, Mark M.; Katayama, Ryohei; McTigue, Michele; Liu, Wei; Deng, Ya-Li; Brooun, Alexei; Friboulet, Luc; Huang, Donghui; Falk, Matthew D.; Timofeevski, Sergei; Wilner, Keith D.; Lockerman, Elizabeth L.; Khan, Tahsin M.; Mahmood, Sidra; Gainor, Justin F.; Digumarthy, Subba R.; Stone, James R.; Mino-Kenudson, Mari; Christensen, James G.; Iafrate, A. John; Engelman, Jeffrey A.; Shaw, Alice T.

2013-01-01

Summary Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74–ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the meta-static sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.) PMID:23724914

Matrix control of pancreatic cancer: New insights into fibronectin signaling.

PubMed

Topalovski, Mary; Brekken, Rolf A

2016-10-10

Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease that resists most current therapies. A defining characteristic of PDA is an intense fibrotic response that promotes tumor cell invasion and chemoresistance. Efforts to understand the complex relationship between the tumor and its extracellular network and to therapeutically perturb tumor-stroma interactions are ongoing. Fibronectin (FN), a provisional matrix protein abundant in PDA stroma but not normal tissues, supports metastatic spread and chemoresistance of this deadly disease. FN also supports angiogenesis, which is required for even hypovascular tumors such as PDA to develop and progress. Targeting components of the tumor stroma, such as FN, can effectively reduce tumor growth and spread while also enhancing delivery of chemotherapy. Here, we review the molecular mechanisms by which FN drives angiogenesis, metastasis and chemoresistance in PDA. In light of these new findings, we also discuss therapeutic strategies to inhibit FN signaling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Esophagogastric metaplasia relates to nodal metastases in adenocarcinoma of esophagus and cardia.

PubMed

Ruffato, Alberto; Mattioli, Sandro; Perrone, Ottorino; Lugaresi, Marialuisa; Di Simone, Massimo Pierluigi; D'Errico, Antonietta; Malvi, Deborah; Aprile, Maria Rosaria; Raulli, Giandomenico; Frassineti, Luca

2013-04-01

Immunohistochemical profiles of esophageal and cardia adenocarcinoma differ according to the presence or absence of Barrett's epithelium (BIM) and gastric intestinal metaplasia (GIM) in the fundus and antrum. Different lymphatic spreading has been demonstrated in esophageal adenocarcinoma. We investigated the correlation among the presence or absence of intestinal metaplasia in the esophagus and stomach and lymphatic metastases in patients who underwent radical surgery for esophageal and cardia adenocarcinoma. The mucosa surrounding the adenocarcinoma and the gastric mucosa were analyzed. The BIM+ patients underwent subtotal esophagectomy and gastric pull up, and the BIM- patients underwent esophagectomy at the azygos vein, total gastrectomy, and esophagojejunostomy. The radical thoracic (station numbers 2, 3, 4R, 7, 8, and 9) and abdominal (station numbers 15 through 20) lymphadenectomy was identical in both procedures except for the greater curvature. One hundred ninety-four consecutive patients were collected in three major groups: BIM+/GIM-, 52 patients (26.8%); BIM-/GIM-, 90 patients (46.4%); BIM-/GIM+, 50 patients (25.8%). Two patients (1%) were BIM+/GIM+. A total of 6,010 lymph nodes were resected: 1,515 were recovered in BIM+, 1,587 in BIM-/GIM+, and 2,908 in BIM-/GIM- patients. The percentage of patients with pN+ stations 8 and 9 was higher in BIM+ (p=0.001), and the percentage of patients with pN+ perigastric stations was higher in BIM- (p=0.001). The BIM-/GIM- patients had a number of abdominal metastatic lymph nodes higher than did the BIM-/GIM+ patients (p=0.0001). According to the presence or absence of BIM and GIM in the esophagus and cardia, adenocarcinoma correspond to three different patterns of lymphatic metastasization, which may reflect different biologic and carcinogenetic pathways. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A new receptor tyrosine kinase inhibitor, icotinib, for patients with lung adenocarcinoma cancer without indication for chemotherapy.

PubMed

Zheng, Xiao; Liu, Guan; Wang, Shengye; Zhang, Yunli; Bao, Wenlong; Deng, Dehou; Mao, Weiming; Fang, Meiyu

2014-10-01

Epidermal growth factor receptor (EGFR) is an important therapeutic target in lung cancer. Gefitinib and erlotinib, two reversible EGFR receptor tyrosine kinases inhibitors (TKIs), have been approved for the treatment of patients with metastatic non small-cell lung cancer. Icotinib, which is a selective EGFR-TKI, provides a similar efficacy to gefitinib. The present study aimed to investigate the survival and safety of icotinib in patients with lung adenocarcinoma with a poor performance status (PS). A total of 42 cases of lung adenocarcinoma, including 35 females and 7 males, were enrolled. Icotinib was used as the first-line of treatment due to poor PS of the patient or a more advanced age. Icotinib (125 mg) was orally administered three times per day. The overall response rate and disease control rates were 33.3 and 85.7%, respectively. The median survival time was 13.0 months (95% CI, 5.6-20.4), The median progression-free survival time was 7.0 months, and the 1-year survival rate was 71.4%. A total of 79% of patients had an improved PS following icotinib treatment. Grade 1 to 2 rashes and diarrhea were the most frequent side effects. One patient succumbed during the study due to interstitial pneumonia. In conclusion, this is the first study indicating that patients with lung adenocarcinoma and poor PS may benefit from first-line icotinib therapy, but should be cautious of the occurrence of interstitial lung disease.

Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

ClinicalTrials.gov

2015-09-28

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

A case report of apatinib in treating osteosarcoma with pulmonary metastases.

PubMed

Zhou, Yong; Zhang, Wengeng; Tang, Fan; Luo, Yi; Min, Li; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

2017-04-01

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Pulmonary metastases lead to a significantly increased risk of death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast cancer. However, its efficacy in metastatic osteosarcoma has not been reported yet. Herein, we presented a 50-year-old man patient who visited hospital due to local bone pain in the left leg. He was initially diagnosed with osteoblastic osteosarcoma. The patient suffered repeated resection surgeries but developed multiple lung metastases. Positive staining for CD31, CD34, and VEGFR-2 were detected in the tumor section. As he refused to receive chemotherapy due to concerns regarding the chemotherapy toxicities and sorafenib due to high cost, apatinib was given at a dose of 500 mg daily. Eleven months following apatinib administration, the patient achieved a partial response according to the RECIST 1.1 standard. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of metastatic osteosarcoma. Clinical trials are required to further confirm the efficacy and safety of apatinib in treating pulmonary metastases from osteosarcoma.

A case report of apatinib in treating osteosarcoma with pulmonary metastases

PubMed Central

Zhou, Yong; Zhang, Wengeng; Tang, Fan; Luo, Yi; Min, Li; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

2017-01-01

Abstract Rationale: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Pulmonary metastases lead to a significantly increased risk of death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast cancer. However, its efficacy in metastatic osteosarcoma has not been reported yet. Patient concerns: Herein, we presented a 50-year-old man patient who visited hospital due to local bone pain in the left leg. Diagnoses: He was initially diagnosed with osteoblastic osteosarcoma. Interventions: The patient suffered repeated resection surgeries but developed multiple lung metastases. Positive staining for CD31, CD34, and VEGFR-2 were detected in the tumor section. As he refused to receive chemotherapy due to concerns regarding the chemotherapy toxicities and sorafenib due to high cost, apatinib was given at a dose of 500 mg daily. Outcomes: Eleven months following apatinib administration, the patient achieved a partial response according to the RECIST 1.1 standard. No severe toxicity or drug-related side effect was observed during the treatment. Lessons: Therefore, apatinib could be a new option for the treatment of metastatic osteosarcoma. Clinical trials are required to further confirm the efficacy and safety of apatinib in treating pulmonary metastases from osteosarcoma. PMID:28403086

Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

PubMed

Perets, Ruth; Greenberg, Orli; Shentzer, Talia; Semenisty, Valeria; Epelbaum, Ron; Bick, Tova; Sarji, Shada; Ben-Izhak, Ofer; Sabo, Edmond; Hershkovitz, Dov

2018-05-01

Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an efficient ctDNA marker for PDAC monitoring. Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival. Plasma KRAS mutations were detected in 5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival. Our results confirm that mutant KRAS ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring. Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers, suggest that ctDNA can be an effective marker for disease monitoring and that ctDNA level over time is a better predictor of survival than the dynamics of the commonly used biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring PDAC treatment response. These results should be further validated in larger sample numbers. © AlphaMed Press 2018.

Correlating confocal microscopy and atomic force indentation reveals metastatic cancer cells stiffen during invasion into collagen I matrices

NASA Astrophysics Data System (ADS)

Staunton, Jack R.; Doss, Bryant L.; Lindsay, Stuart; Ros, Robert

2016-01-01

Mechanical interactions between cells and their microenvironment dictate cell phenotype and behavior, calling for cell mechanics measurements in three-dimensional (3D) extracellular matrices (ECM). Here we describe a novel technique for quantitative mechanical characterization of soft, heterogeneous samples in 3D. The technique is based on the integration of atomic force microscopy (AFM) based deep indentation, confocal fluorescence microscopy, finite element (FE) simulations and analytical modeling. With this method, the force response of a cell embedded in 3D ECM can be decoupled from that of its surroundings, enabling quantitative determination of the elastic properties of both the cell and the matrix. We applied the technique to the quantification of the elastic properties of metastatic breast adenocarcinoma cells invading into collagen hydrogels. We found that actively invading and fully embedded cells are significantly stiffer than cells remaining on top of the collagen, a clear example of phenotypical change in response to the 3D environment. Treatment with Rho-associated protein kinase (ROCK) inhibitor significantly reduces this stiffening, indicating that actomyosin contractility plays a major role in the initial steps of metastatic invasion.

Well-differentiated neuroendocrine tumors in skin: Terminology and diagnostic utility of cytokeratin 5/6 and p63.

PubMed

Panse, Gauri; Cowper, Shawn E; Leffell, David J; Pulitzer, Melissa; Ko, Christine J

2017-06-01

Well-differentiated neuroendocrine tumors (WDNETs) in skin include metastases from visceral primary sites and very uncommonly, primary cutaneous carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in particular can be mistaken for a benign skin adnexal tumor. In contrast to cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin 5/6 (CK5/6) and p63 negative in the majority of cases. It is unclear if failure to stain with CK5/6 and p63 would be helpful in differentiating WDNETs from cutaneous adnexal neoplasms. We reviewed 10 cases of cutaneous WDNETs (8 cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin) and performed immunohistochemical stains for CK5/6 and p63 on all cases. All 10 cases were negative with both CK5/6 and p63. Negative staining for CK5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal neoplasms. It is important to consider WDNETs in the differential diagnosis of cutaneous adnexal neoplasms as low-grade tumors may be the first sign of aggressive metastatic disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

PubMed

Ma, Jian; Yang, Quan-Liang; Ling, Yang

2017-02-14

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

PubMed

Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

2016-10-01

Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Necrotizing Infundibular Crystalline Folliculitis (NICF) Induced by Anti-Tumoral Therapies: Report of 2 Cases.

PubMed

Fattouh, Kinda; Collet-Benzaquen, Diane; Provensal, Anne M; Desseigne, Françoise; Castillo, Christine; Combemale, Patrick; de la Fouchardière, Arnaud

2017-10-01

Necrotizing Infundibular Crystalline Folliculitis (NICF) is rare entity of unknown pathogenesis presenting as follicular crystalline papules arising in seborrheic areas. We report 2 cases of NICF in patients under targeted therapy for metastatic adenocarcinoma. In one case, the lesions reappeared cyclically every 3 weeks after each injection and in the other case, lesions persisted until disruption of the continuous oral therapy. Punch-biopsies demonstrated folliculitis with a plugging crystalline material associated with either bacteria or yeast. These are the first descriptions of drug-induced NICF.

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

PubMed

Shield, Paul W; Papadimos, David J; Walsh, Michael D

2014-04-01

The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration. © 2014 American Cancer Society.

Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.

PubMed

Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel

2016-08-09

Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a viable alternative to the current standard-of-care nab-PTX plus GEM regimen for the treatment of PDAC patients.

Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival.

PubMed

Faluyi, Olusola O; Eng, Lawson; Qiu, Xin; Che, Jiahua; Zhang, Qihuang; Cheng, Dangxiao; Ying, Nanjiao; Tse, Alvina; Kuang, Qin; Dodbiba, Lorin; Renouf, Daniel J; Marsh, Sharon; Savas, Sevtap; Mackay, Helen J; Knox, Jennifer J; Darling, Gail E; Wong, Rebecca K S; Xu, Wei; Azad, Abul Kalam; Liu, Geoffrey

2017-02-01

Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04-1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53-0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28-0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03-1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01-1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Targeted treatment of mutated EGFR-expressing non-small-cell lung cancer: focus on erlotinib with companion diagnostics

PubMed Central

Karachaliou, Niki; Rosell, Rafael

2014-01-01

Deeper understanding of the pathobiology of non-small-cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in the progression to metastatic disease. The discovery of epidermal growth factor receptor (EGFR) mutations in 15%–20% of lung adenocarcinomas and the associated response to EGFR tyrosine kinase inhibitors have provided a successful avenue of attack in late-stage adenocarcinomas. Use of the EGFR tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib is limited to patients who have adenocarcinomas with known activating EGFR mutations. However, the EGFR mutation testing landscape is varied and includes many screening and targeted methods, each with its own benefits and limitations. These tests can simplify the drug discovery process, make clinical trials more efficient and informative, and individualize cancer therapy. In practice, the choice of method should be determined by the nature of the sample to be tested, the testing laboratory’s expertise and access to equipment, and whether the detection of only known activating EGFR mutations, or of all possible mutations, is required. Development of companion diagnostic tests for this identification is advancing; nevertheless, the use of such tests merits greater attention. PMID:28210145

Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

PubMed

Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

2016-02-01

Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

ClinicalTrials.gov

2018-06-04

Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Small Cell Lung Carcinoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Small Cell Lung Carcinoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Small Cell Lung Carcinoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Small Cell Lung Carcinoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Pancreatic Carcinoma

Metastasis to the pancreas and stomach from a breast cancer primary: a case report.

PubMed

Kliiger, Jason; Gorbaty, Mayer

2017-10-01

A 60-year-old female with an unknown family history initially presented with signs and symptoms concerning for gastrointestinal cancer. Regular breast cancer screening and subsequent work-up around this time demonstrated the presence of T2N1 stage II triple positive ductal adenocarcinoma of the left breast. Follow-up imaging for her gastrointestinal symptoms demonstrated a 3.5 cm solitary mass in the pancreas and diffuse thickening of the stomach wall. Biopsies of the gastrointestinal lesions were identified as metastatic foci of the breast cancer primary. Breast cancer metastases to the stomach and to the pancreas are both very rare events. Of the breast cancer primaries that do metastasize to the gastrointestinal system, it is unusual for the primary to be ductal adenocarcinoma. The rapid succession of diagnosing the primary source of breast cancer simultaneously with its metastases is also unusual. Timely identification and appropriate management of these rare metastases was made possible due to routine breast cancer screening.

Comparison of abdominal ultrasound and magnetic resonance imaging for detection of abdominal lymphadenopathy in dogs with metastatic apocrine gland adenocarcinoma of the anal sac.

PubMed

Anderson, C L; MacKay, C S; Roberts, G D; Fidel, J

2015-06-01

Imaging studies in humans with anal and rectal cancer indicate that magnetic resonance imaging (MRI) is a more sensitive technique than abdominal ultrasound (AUS) for the detection of abdominal lymphadenopathy. The purpose of this retrospective study was to directly compare the efficacy of these two techniques in detecting abdominal lymphadenopathy in dogs with apocrine gland adenocarcinoma of the anal sac (AGAAS). Six dogs with histologically confirmed AGAAS and histopathologic confirmation of metastasis to abdominal lymph nodes (LNs) had AUS and abdominal MRI. AUS identified lymphadenopathy in two of six dogs, whereas MRI identified lymphadenopathy in all the six dogs. Lymphadenopathy was predominantly sacral in location, with involvement of the medial iliac and hypogastric LNs in only two cases. These data suggest that MRI is more sensitive than AUS for detecting sacral abdominal lymphadenopathy in dogs with AGAAS. As such, MRI could be considered in any patient with AGAAS for initial staging of this disease. © 2013 Blackwell Publishing Ltd.

Diabetes Insipidus: An Unusual Presentation of Adenocarcinoma of the Lung in a Patient with no Identifiable Lung Mass.

PubMed

Gulati, Shuchi; Kiefer, Christoper; Karim, Nagla Abdel

2015-10-01

Lung cancers are known to metastasize to unusual sites. Despite this knowledge often times the diagnosis of a primary lung cancer gets delayed especially when the patient presents without respiratory symptoms. The patient discussed in our review is a 47-year-old female, smoker who had presented to several hospitals with months of headache, nausea and intermittent episodes of vomiting. She was noted to have hypernatremia due to diabetes insipidus and a pituitary lesion on her magnetic resonance images. The pituitary mass on biopsy was found to represent a metastatic focus from a primary lung adenocarcinoma. Clinicians should be aware of malignancies that are well known to metastasize to the posterior pituitary. Conversely, since not every patient presents with symptoms of metastasis, there is a need to recognize the clinical syndromes (e. g., diabetes insipidus-like symptoms or more subtle symptoms like cranial nerve palsies) associated with potential metastasis to the pituitary.

Vaginal stump metastasis from sigmoid colon cancer.

PubMed

Tanaka, Tomohito; Kanda, Takayoshi; Sakaguchi, Satoru; Munakata, Satoru; Ohmichi, Masahide

2012-01-01

Vaginal metastasis from organs other than the uterus is rare. Generally, patients with vaginal metastasis from colorectal cancer have a dismal prognosis. Although biopsy is the best method to make the diagnosis, massive bleeding may occur. On the other hand, liquid-based cytology (LBC) has the utility to perform immunocytochemistry on additional unstained slides: we can make a diagnosis with several immunocytochemical findings. A 67-year-old postmenopausal female presented to our hospital with vaginal bleeding. The patient had undergone colectomy because of her stage III sigmoid colon cancer 3 years earlier. The patient had also undergone hysterectomy for cervical cancer 30 years earlier. LBC from the vaginal stump revealed adenocarcinoma. Immunocytochemically, cancer cells were negative for cytokeratin 7 and positive for cytokeratin 20, which suggested metastasis from the sigmoid colon cancer; the diagnosis was made without a biopsy. When the patient has a metastatic lesion from colon adenocarcinoma, LBC with immunocytochemistry is useful in making a diagnosis. Copyright © 2012 S. Karger AG, Basel.

Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey

PubMed Central

Afrin, Sadia; Forbes-Hernandez, Tamara Y.; Gasparrini, Massimiliano; Bompadre, Stefano; Quiles, José L.; Sanna, Gavino; Spano, Nadia; Giampieri, Francesca; Battino, Maurizio

2017-01-01

Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree (Arbutus unedo) honey (STH) and its cytotoxic properties against human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cell lines in comparison with Manuka (Leptospermum scoparium) honey (MH). Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS) generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer. PMID:28287469

Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma Reveals an Atypical Presentation of Li-Fraumeni Syndrome

PubMed Central

Chang, Vivian Y.; Federman, Noah; Martinez-Agosto, Julian; Tatishchev, Sergei F.; Nelson, Stanley F.

2014-01-01

Background Gastric adenocarcinoma is a rare diagnosis in childhood. A 14-year old male patient presented with metastatic gastric adenocarcinoma, and a strong family history of colon cancer. Clinical sequencing of CDH1 and APC were negative. Whole exome sequencing was therefore applied to capture the majority of protein-coding regions for the identification of single-nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient’s germline as well as primary tumor. Materials and Methods DNA was extracted from the patient’s blood, primary tumor, and the unaffected mother’s blood. DNA libraries were constructed and sequenced on Illumina HiSeq2000. Data were post-processed using Picard and Samtools, then analyzed with the Genome Analysis Toolkit. Variants were annotated using an in-house Ensembl-based program. Copy number was assessed using ExomeCNV. Results Each sample was sequenced to a mean depth of coverage of greater than 120×. A rare non-synonymous coding SNV in TP53 was identified in the germline. There were 10 somatic cancer protein-damaging variants that were not observed in the unaffected mother genome. ExomeCNV comparing tumor to the patient’s germline, identified abnormal copy number, spanning 6,946 genes. Conclusion We present an unusual case of Li-Fraumeni detected by whole exome sequencing. There were also likely driver somatic mutations in the gastric adenocarcinoma. These results highlight the need for more thorough and broad scale germline and cancer analyses to accurately inform patients of inherited risk to cancer and to identify somatic mutations. PMID:23015295

Comparative study of the radical and standard lymphadenectomy in the surgical treatment of adenocarcinoma of the ampula of Vater.

PubMed

Albagli, Rafael Oliveira; Carvalho, Gustavo Santos Stoduto de; Mali Junior, Jorge; Eulálio, José Marcos Raso; de Melo, Eduardo Linhares Rielo

2010-12-01

To evaluate the morbidity and mortality in patients undergoing surgical pancreatoduodenectomy (PD) in standard and radical lymphadenectomy for adenocarcinoma of papilla, analyzing the prognostic factors related to overall and disease-free survival. Were analyzed retrospectively from 1999 to 2007, in the Department of Abdominal and Pelvic Surgery (INCa-RJ), 50 cases of PD for adenocarcinoma of the duodenal papilla divided into two groups according to lymphadenectomy (group A: standard lymphadenectomy and group B: radical lymphadenectomy). The median age was similar in both groups, as well as the distribution between the sex. In the comparison between the lymphadenectomies, only the number of lymph nodes resected (group A: 12.3 and group B: 26.5) and operative time (group A: 421 and group B: 474) were significantly different. There were no statistically significant differences in the two groups with respect to morbidity and mortality rate and length of hospitalization. The disease-free survival (group A: 35 months and group B: 51 months) and overall survival (group A: 38 months and group B: 53 months) was higher in the group of radical lymphadenectomy, but were not statistically significant. In this study there were no cases of metastatic lymph nodes to other groups without nodal involvement of the pancreatic-duodenal lymph node chains (13, 17), suggesting a pattern of lymph node spread. Despite the radical lymphadenectomy present rates of disease-free survival and overall survival largest such data were not statistically significant. Further studies should be conducted to evaluate the real role of radical lymphadenectomy in adenocarcinoma of the duodenal papilla.

Metastatic mediastinal mature teratoma with malignant transformation in a young man with an adenocarcinoma in a Klinefelter's syndrome: Case report and review of the literature.

PubMed

Le Fèvre, C; Vigneron, C; Schuster, H; Walter, A; Marcellin, L; Massard, G; Lutz, P; Noël, G

2018-05-01

Malignant transformation of mediastinal mature teratoma is extremely rare and worsens the prognosis of the disease. Transformation can appear synchronously to or several years after the initial diagnosis. Clinical and radiological signs can orientate the clinician but the definitive diagnosis is obtained thanks to histology. An 11 year-old boy presented with a mediastinal mature teratoma and bone and pulmonary metastases. He received six cycles of chemotherapy combining etoposide, ifosfamide, cisplatin, followed by resection of a 16×14×9cm mediastinal mass. Karyotype analysis revealed the presence of an additional sex chromosome X (47 XXY) pathognomonic of Klinefelter's syndrome. Ten years later, sciatalgia revealed malignant transformation of a pre-existing sacral bone metastasis into gastrointestinal adenocarcinoma. The patient received four cycles of chemotherapy combining oxaliplatin, 5-fluorouracil and cetuximab. This treatment was followed by a complete resection of the sacral metastasis and completed with adjuvant irradiation of 54Gy in 30 daily fractions. Twelve months after the diagnosis of relapse, the patient remained alive without disease. To our knowledge, this is the first case of adenocarcinoma developed in bone metastases of a mediastinal mature teratoma in a boy with a Klinefelter's syndrome. We propose a review of the literature and an analysis of 20 others published cases of mediastinal teratoma with malignant transformation into adenocarcinoma. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Advanced pancreatic adenocarcinoma outcomes with transition from devolved to centralised care in a regional Cancer Centre.

PubMed

Faluyi, Olusola O; Connor, Joanna L; Chatterjee, Madhuchanda; Ikin, Carl; Wong, Helen; Palmer, Daniel H

2017-02-14

Previous observations suggest suboptimal 'real world' survival outcomes for advanced pancreatic adenocarcinoma. We hypothesized that centralisation of advanced pancreatic adenocarcinoma management would improve chemotherapy treatment and survival from the disease. The data was prospectively collected on all cases of advanced pancreatic adenocarcinoma reviewed through Clatterbridge Cancer Centre according to two groups; 1 October 2009-31st Dec 2010 (devolved care) or 1 January 2013-31 March 2014 (centralised care). Analysis included treatment received, 30-day chemotherapy mortality rate and overall survival (OS). More patients received chemotherapy with central care (67.0% (n=115) vs 43.0% (n=121); P=2.2 × 10 -4 ) with no difference in 30-day mortality (20.8% vs 25%; P=0.573) but reduced time to commencement of chemotherapy (18 vs 28 days, P=1.0 × 10 -3 ). More patients received second-line chemotherapy with central care (23.4% vs 1.9%, P=1.4 × 10 -4 ), while OS was significantly increased with central care (median: Five vs three months, HR 0.785, P=0.045). Exploratory analysis suggested that it was those with a poorer performance status, elderly or with metastatic disease who benefited the most from transition to central care. A centralised clinic model for advanced pancreatic cancer management resulted in prompt, safe and higher use of chemotherapy compared with devolved care. This was associated with a modest survival benefit. Prospective studies are required to validate the findings reported and the basis for improved survival with centralised care.

Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung.

PubMed

Semba, Seitaro; Iwaya, Keiichi; Matsubayashi, Jun; Serizawa, Hiromi; Kataba, Hiroaki; Hirano, Takashi; Kato, Harubumi; Matsuoka, Takeshi; Mukai, Kiyoshi

2006-04-15

Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar carcinomas (P < 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time (P < 0.0001) and overall survival time (P < 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.

Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma

PubMed Central

PALIOGIANNIS, PANAGIOTIS; ATTENE, FEDERICO; COSSU, ANTONIO; DEFRAIA, EFISIO; PORCU, GIUSEPPE; CARTA, ANNAMARIA; SOTGIU, MARIA IGNAZIA; PAZZOLA, ANTONIO; CORDERO, LORENZO; CAPELLI, FRANCESCA; FADDA, GIOVANNI MARIA; ORTU, SALVATORE; SOTGIU, GIOVANNI; PALOMBA, GRAZIA; SINI, MARIA CRISTINA; PALMIERI, GIUSEPPE; COLOMBINO, MARIA

2015-01-01

Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. A total of 515 patients with histologically-confirmed disease were included in the present study. Formalin-fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. Genomic DNA was isolated using a standard protocol. The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. The mean age of the patients examined was 64.9 years and 357 (69.3%) were male. A total of 429 tissue samples (83.3%) were obtained by biopsy and the remaining samples were obtained by surgery. A total of 456 samples (88.5%) were observed from primary lung adenocarcinomas, while 59 (11.5%) were from metastatic lesions. EGFR mutations occurred in 59 cases (11.5%); exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. EGFR mutations were more frequent in females and patients that had never smoked. The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. However, a statistically significant difference in the number of mutations detected was found between samples with at least 50% of neoplastic cells (450 cases-57 mutations; 12.7%) and those with <50% of neoplastic cells (65 cases-2 mutations; 3.1%). PMID:25683726

Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow.

PubMed

Wittchow, R; Laszewski, M; Walker, W; Dick, F

1992-09-01

Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory.

Metastatic gastric carcinoma from breast cancer mimicking primary linitis plastica: A case report.

PubMed

Yagi, Yasumichi; Sasaki, Shozo; Yoshikawa, Akemi; Tsukioka, Yuji; Fukushima, Wataru; Fujimura, Takashi; Hirosawa, Hisashi; Izumi, Ryohei; Saito, Katsuhiko

2015-12-01

Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer.

PubMed

Goddard, Erica T; Fischer, Jacob; Schedin, Pepper

2016-12-26

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.

PubMed

Bullman, Susan; Pedamallu, Chandra S; Sicinska, Ewa; Clancy, Thomas E; Zhang, Xiaoyang; Cai, Diana; Neuberg, Donna; Huang, Katherine; Guevara, Fatima; Nelson, Timothy; Chipashvili, Otari; Hagan, Timothy; Walker, Mark; Ramachandran, Aruna; Diosdado, Begoña; Serna, Garazi; Mulet, Nuria; Landolfi, Stefania; Ramon Y Cajal, Santiago; Fasani, Roberta; Aguirre, Andrew J; Ng, Kimmie; Élez, Elena; Ogino, Shuji; Tabernero, Josep; Fuchs, Charles S; Hahn, William C; Nuciforo, Paolo; Meyerson, Matthew

2017-12-15

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome-including Bacteroides , Selenomonas , and Prevotella species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium -associated colorectal cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity.

PubMed

Sharbeen, George; Youkhana, Janet; Mawson, Amanda; McCarroll, Joshua; Nunez, Andrea; Biankin, Andrew; Johns, Amber; Goldstein, David; Phillips, Phoebe

2017-02-07

Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread.

Lung cancer diagnosis on ovary mass: a case report

PubMed Central

2013-01-01

Metastatic neoplasms to the ovary often cause diagnostic problems, in particular those large ovarian masses mimicking primary tumors. Most of these tumors arise from digestive system or breast, while 37-year-old woman diagnosed as right adnexal complex mass, with a subpleural nodule in the apical part of the left lower lobe, at preoperative chest computed tomography scan. The patient underwent total abdominal hysterectomy with right salpingo-oophorectomy (ovarian mass 220 × 200 mm), total omentectomy, left ovarian biopsy, peritoneal random biopsies, and peritoneal washings for cytology. Pathologic and immunohistochemical examination of ovarian specimen suggested morphology and expression of metastatic lung adenocarcinoma with an intense positivity for Thyroid Transcriptional Factor-1 (TTF-1) and Cytokeratin 7 (CK7) staining. Fine needle biopsy of the lung nodule found epithelioid like malignant cells, confirming the diagnosis of an ovarian metastasis from a primary lung cancer. This report focused on the clinical and pathologic diagnostic challenge of distinguishing secondary from primary ovarian neoplasms. Issues on useful immunohistochemical stains are also discussed. PMID:23663245

An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma

PubMed Central

Benson, Al; Yaghmai, Vahid; Costa, Ricardo L. B.; Zhou, Haijun; Behdad, Amir; Kaplan, Jason B.; Sadim, Maureen; Talamantes, Sarah; Kalyan, Aparna

2018-01-01

Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS) for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case. PMID:29808141

Bilateral ethmoid sinusitis with unilateral proptosis as an initial manifestation of metastatic prostate carcinoma.

PubMed Central

Fortson, J. K.; Bezmalinovic, Z. L.; Moseley, D. L.

1994-01-01

This article presents a case of bilateral ethmoid sinusitis with unilateral proptosis as a presenting sign of an unsuspected prostate carcinoma. A 59-year-old Hispanic male presented to his primary care physician with nasal congestion and rhinitis. He was treated with antibiotics and antihistamine decongestants for 3 weeks without improvement. A trial of steroids resulted in brief improvement followed by a rapid onset of nasal obstruction with proptosis. A computed tomography scan revealed opacification of the ethmoid sinus with right proptosis. The presumptive diagnosis was orbital cellulitis secondary to chronic ethmoid sinusitis. Endoscopic sinusotomy and bilateral ethmoidectomies were performed. Biopsy results returned as metastatic adenocarcinoma, probably of prostate origin. Urological work-up and evaluation with biopsy confirmed the diagnosis of prostatic carcinoma. The patient was treated with chemotherapy and radiation therapy. He died 7 months later with disseminated disease. Images Figure 1 Figure 2 Figure 3 Figure 4A Figure 4B PMID:7861473

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

PubMed

Bustamante, Carmen; Hoyos-Martínez, Alfonso; Pirela, Daniela; Díaz, Alejandro

2017-07-26

Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.

A Case of Metachronous Metastasis to the Breast from Non-Small Cell Lung Carcinoma

PubMed Central

Yoon, Min Yong; Song, Chang Seok; Seo, Mi Hae; Kim, Min Jae; Oh, Tae Yun; Jang, Un Ha; Kwag, Hyon Joo; Kim, Hee Sung; Lim, Si Young; Lim, Seong Yong

2010-01-01

Breast metastases from an extramammary primary tumor are very rare and the prognosis for such patients is generally poor. We report here on a case of a 42-year-old female with metastasis of non-small cell lung cancer to the breast, and she is now being followed up on an outpatient basis. In 2004, she presented with a solitary pulmonary nodule in the left lung, and this lesion had been noted to have gradually increased in size over time. The final pathological diagnosis was adenocarcinoma, and the diagnosis was made by performing percutaneous needle aspiration and lobectomy of the left upper lobe. Adjuvant chemotherapy and radiotherapy were given. Unfortunately, a nodule in the left breast was noted three years later, and metastatic non-small-cell lung cancer to the breast was diagnosed by excisional biopsy. Making the correct diagnosis to distinguish a primary breast carcinoma from a metastatic one is important, because the therapeutic plan and outcome for these two types of cancer are quite different. PMID:20948923

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer

PubMed Central

Smolle, Maria A.; Bauernhofer, Thomas; Pummer, Karl; Calin, George A.; Pichler, Martin

2017-01-01

The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread. PMID:28241429

The Role of BRCA1 in Normal Mammary Epithelial Development and Tumorigenesis.

DTIC Science & Technology

1999-06-01

addition, a hemangiosarcoma was found in one of the Brcal’’~p53~’~ mice. Cell lines were generated from each of these tumors. Generation and...19 10 45.2 23.8 2/9 0/5 Hemangiosarcoma Cerebellar developmental defect Adenocarcinoma of the Hardarian gland 3 2 1 5.9 3.9 2.0 2 4.8...17.4 0/2 Hemangiosarcoma 2 8.7 Squamous cell carcinoma 1 4.3 Benign spindle cell tumor 1 4.3 No visible or metastatic tumors at death 3 15.8 3 13.0

Isolated Hepatic Metastasis from Prostate Carcinoma.

PubMed

Wang, Stephani C; McCarthy, Lezah P; Mehdi, Syed

2017-01-01

Worldwide, prostate cancer is considered the second most common cancer in men. Most common sites for metastatic disease are lymph nodes and bones. However, isolated liver metastasis from prostate cancer is rare. We present a 75 year-old male with prostate adenocarcinoma diagnosed 7 years ago. With rising PSA, he underwent imaging and found to have isolated hepatic metastasis. After left hepatic lobectomy, his PSA dramatically decreased to < 0.01. Physicians should be aware of isolated hepatic metastasis in patients with prostate cancer. Metastasectomy should be considered in such case, and combined medical and surgical approach may prolong the overall survival.

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeman, Jonathan E.; Rimner, Andreas; Montecalvo, Joseph

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. Methods and Materials: We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 Worldmore » Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non–high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score–weighted Cox regression models. Results: The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non–high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. Conclusions: The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have important implications for patient selection, adjuvant treatment, biopsy methods, and clinical trial design.« less

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy.

PubMed

Leeman, Jonathan E; Rimner, Andreas; Montecalvo, Joseph; Hsu, Meier; Zhang, Zhigang; von Reibnitz, Donata; Panchoo, Kelly; Yorke, Ellen; Adusumilli, Prasad S; Travis, William; Wu, Abraham J

2017-01-01

Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 World Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non-high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score-weighted Cox regression models. The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non-high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have important implications for patient selection, adjuvant treatment, biopsy methods, and clinical trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Imaging for Guiding Oncologic Prognosis and Therapy in Esophageal Adenocarcinoma

PubMed Central

Yentz, Sarah; Wang, Thomas D.

2011-01-01

In the last 30 years, the incidence of esophageal adenocarcinoma has skyrocketed. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal adenocarcinoma remains poor with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because “alarm symptoms” such as dysphagia occur at a late stage, and 2) high-grade dysplasia (HGD) and early adenocarcinoma (ACA) are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to adenocarcinoma because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease, and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance and treatment. Targeted agents against EGFR, HER2/neu and VEGF are currently being evaluated for their role in combination chemotherapy for metastatic esophageal adenocarcinoma. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell surface receptors, and has the potential to evaluate an individual patient’s gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for truly personalized treatment in the future. PMID:21576902

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.

PubMed

Court, Colin M; Ankeny, Jacob S; Sho, Shonan; Winograd, Paul; Hou, Shuang; Song, Min; Wainberg, Zev A; Girgis, Mark D; Graeber, Thomas G; Agopian, Vatche G; Tseng, Hsian-Rong; Tomlinson, James S

2018-04-01

Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040). CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

Prophylactic Dendritic Cell-Based Vaccines Efficiently Inhibit Metastases in Murine Metastatic Melanoma.

PubMed

Markov, Oleg V; Mironova, Nadezhda L; Sennikov, Sergey V; Vlassov, Valentin V; Zenkova, Marina A

2015-01-01

Recent data on the application of dendritic cells (DCs) as anti-tumor vaccines has shown their great potential in therapy and prophylaxis of cancer. Here we report on a comparison of two treatment schemes with DCs that display the models of prophylactic and therapeutic vaccination using three different experimental tumor models: namely, Krebs-2 adenocarcinoma (primary tumor), melanoma (B16, metastatic tumor without a primary node) and Lewis lung carcinoma (LLC, metastatic tumor with a primary node). Dendritic cells generated from bone marrow-derived DC precursors and loaded with lysate of tumor cells or transfected with the complexes of total tumor RNA with cationic liposomes were used for vaccination. Lipofectamine 2000 and liposomes consisting of helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and cationic lipid 2D3 (1,26-Bis(1,2-de-O-tetradecyl-rac-glycerol)-7,11,16,20-tetraazahexacosan tetrahydrocloride) were used for RNA transfection. It was shown that DCs loaded with tumor lysate were ineffective in contrast to tumor-derived RNA. Therapeutic vaccination with DCs loaded by lipoplexes RNA/Lipofectamine 2000 was the most efficient for treatment of non-metastatic Krebs-2, where a 1.9-fold tumor growth retardation was observed. Single prophylactic vaccination with DCs loaded by lipoplexes RNA/2D3 was the most efficient to treat highly aggressive metastatic tumors LLC and B16, where 4.7- and 10-fold suppression of the number of lung metastases was observed, respectively. Antimetastatic effect of single prophylactic DC vaccination in metastatic melanoma model was accompanied by the reductions in the levels of Th2-specific cytokines however the change of the levels of Th1/Th2/Th17 master regulators was not found. Failure of double prophylactic vaccination is explained by Th17-response polarization associated with autoimmune and pro-inflammatory reactions. In the case of therapeutic DC vaccine the polarization of Th1-response was found nevertheless the antimetastatic effect was less effective in comparison with prophylactic DC vaccine.

A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.

PubMed

Wang, Feng-Hua; Wang, Yun; Chen, Zhen-Dong; Chen, Jian-Hua; Qin, Feng-Zhan; Jiang, Wen-Qi; Li, Yu-Hong

2016-11-01

Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m 2 /d and 20 µg/m 2 /d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m 2 /d rhLTα-Da followed by DDP (15 mg/m 2 /d) and 5-Fu (750 mg/m 2 /d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m 2 /d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m 2 /d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m 2 /d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.

The T-LAK Cell-originated Protein Kinase Signal Pathway Promotes Colorectal Cancer Metastasis.

PubMed

Zykova, Tatyana A; Zhu, Feng; Wang, Lei; Li, Haitao; Bai, Ruihua; Lim, Do Young; Yao, Ke; Bode, Ann M; Dong, Zigang

2017-04-01

Approximately 90% of all cancer deaths arise from the metastatic dissemination of primary tumors. Metastasis is the most lethal attribute of colorectal cancer. New data regarding the molecules contributing to the metastatic phenotype, the pathways they control and the genes they regulate are very important for understanding the processes of metastasis prognosis and prevention in the clinic. The purpose of this study was to investigate the role of T-LAK cell-originated protein kinase (TOPK) in the promotion of colorectal cancer metastasis. TOPK is highly expressed in human metastatic colorectal cancer tissue compared with malignant adenocarcinoma. We identified p53-related protein kinase (PRPK) as a new substrate of TOPK. TOPK binds with and phosphorylates PRPK at Ser250 in vitro and ex vivo. This site plays a critical role in the function of PRPK. Cell lines stably expressing mutant PRPK (S250A), knockdown TOPK, knockdown PRPK or knockdown of both TOPK and PRPK significantly inhibited liver metastasis of human HCT116 colon cancer cells in a xenograft mouse model. Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. Thus, these findings may assist in the prediction of prognosis or development of new therapeutic strategies against colon cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

PubMed

Dondossola, Eleonora; Dobroff, Andrey S; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-23

Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell-mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery.

Cooperativity of E-cadherin and Smad4 loss to promote diffuse-type gastric adenocarcinoma and metastasis.

PubMed

Park, Jun Won; Jang, Seok Hoon; Park, Dong Min; Lim, Na Jung; Deng, Chuxia; Kim, Dae Yong; Green, Jeffrey E; Kim, Hark Kyun

2014-08-01

Loss of E-cadherin (CDH1), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre, and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice than in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(+/+) mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. Knockdown of β-catenin significantly inhibited the migratory activity of Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma. This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, providing novel insights into mechanisms for gastric cancer metastasis. ©2014 American Association for Cancer Research.

Metastasis to the penis in a patient with adenocarcinoma of lung, case report and literature review.

PubMed

Zheng, Fu-Fu; Zhang, Zhong-Yun; Dai, Yu-Ping; Liang, Yue-You; Deng, Chun-Hua; Tao, Yu

2009-01-01

Metastasis of lung cancer to the penis is very rare; it causes various clinical symptoms seriously affecting the quality of life. Early recognition and appropriate management will likely enhance survival in these patients. Here, we report a case of penile metastasis secondary to pulmonary carcinoma along with a review of the literature. One case of penile metastasis secondary to pulmonary carcinoma was detected in a 51-year-old patient who was admitted to the First Affiliated Hospital of Sun Yat-Sen University with persistent cough along with swelling of the perineum and penis. The clinical features, diagnosis, and treatment of this disease along with a relevant literature are reviewed and discussed. A MEDLINE search was performed to identify similar reports in the literature. CT scan revealed lung mass, and a glans penis ulcer and enlargement of inguinal lymph nodes was discovered upon physical examination. CT-guided percutaneous puncture of the lung mass revealed adenocarcinoma of lung, and biopsies of the glans penis ulcer and inguinal lymph nodes confirmed metastatic adenocarcinoma. The patients received chemotherapy and died of acute pulmonary embolism in less than 2 months. Metastasis of lung cancer to the penis is extremely rare. It presents an advanced form of lung cancer, and thus survival is extremely short. Although treatment of penile metastasis is almost always palliative, early recognition may enhance survival for these patients.

Small bowel adenocarcinoma of the jejunum: a case report and literature review.

PubMed

Li, Jie; Wang, Zhiliang; Liu, Na; Hao, Junfeng; Xu, Xin

2016-07-04

In practice, small bowel cancer is a rare entity. The most common histologic subtype is adenocarcinoma. Adenocarcinoma of the small bowel (SBA) is challenging to diagnose, often presents at a late stage and has a poor prognosis. The treatment of early-stage SBA is surgical resection. No standard protocol has been established for unresectable or metastatic disease. We report here on a 26-year-old man with SBA in the jejunum, lacking specific symptoms and with a delay of 6 months in diagnosis. The diagnosis was finally achieved with a combination of balloon-assisted enteroscopy, computed tomography scans, positron emission computed tomography scans and the values of carcino-embryonic antigen and carbohydrate antigen 19-9. The patient underwent segmental intestine with lymph node resection, followed by eight cycles of FOLFOX palliative chemotherapy with good tolerance. As of the 11-month postoperative follow-up, there has been no evidence of recurrent disease. This case is reported to arouse a clinical suspicion of SBA in patients with abdominal pain of unknown cause. We also provided evidence in this case of a response to palliative chemotherapy with FOLFOX. Because the incidence of SBA is very low, there is a need for further studies to evaluate the possible application of newer investigative agents and strategies to obtain a better outcome within the framework of international collaborations.

Recurrence of lung adenocarcinoma after an interval of 15 years revealed by demonstration of the same type of EML4-ALK fusion gene.

PubMed

Tsukamoto, Yoshitane; Kanamori, Kiyonobu; Watanabe, Takahiro; Mikami, Koji; Ieki, Ryuji; Nakano, Takashi; Kajimoto, Kazuyoshi; Hirota, Seiichi

2014-12-01

We carried out an experiment on a 58-year-old man with multiple left lung tumors and swelling of multiple lymph nodes. For clinical staging and therapeutic purposes, bronchoalveolar lavage (BAL) cytology and lung biopsy were performed. The biopsy specimen revealed the left lower lung mass to be immunohistochemically ALK (anaplastic lymphoma kinase)-positive adenocarcinoma. Using the BAL specimen from the left lower lung, EML4 (echinoderm microtubule-associated protein-like 4)-ALK variant 1 fusion gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). His past history showed that he had undergone an operation for lung adenocarcinoma of the right lower lobe 15 years before, and the pathological specimen at that time revealed that the lung adenocarcinoma with pleural invasion and single metastasis of mediastinal lymph node showed a mucinous cribriform pattern and/or signet-ring cell pattern. The typical histology led us to examine the ALK rearrangement in the primary lung cancer and mediastinal metastatic tumor. Immunohistochemistry (IHC) for ALK was positive, and ALK break apart fluorescence in situ hybridization (FISH) showed a positive result. Moreover, RT-PCR using formalin-fixed, paraffin-embedded tissue from the right lung cancer also demonstrated EML4-ALK variant 1 fusion gene. Although there is a possibility that the left lung cancer is de novo one with multiple metastases, detection of the same fusion gene of the very rare EML4-ALK variant 1 in both tumors suggests that the left cancer is a recurrence of the right lung cancer after an interval of 15 years. Copyright © 2014 Elsevier GmbH. All rights reserved.

The Frequency of EGFR Mutation in Lung Adenocarcinoma and the Efficacy of Tyrosine Kinase Inhibitor Therapy in a Hungarian Cohort of Patients.

PubMed

Sárosi, Veronika; Balikó, Zoltán; Smuk, Gábor; László, Terézia; Szabó, Mariann; Ruzsics, István; Mezősi, Emese

2016-10-01

In the last decades new therapeutic drugs have been developed for the treatment of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) significantly increase the progression free survival (PFS) of patients with NSCLC carrying epidermal growth factor receptor (EGFR) mutations. This type of lung cancer occurs mainly among non-smoking women and Asian origin. However, the new ESMO guideline recommends EGFR mutation analysis in every patient with NSCLC, because in patients with activating EGFR mutation, TKIs should be considered as first line therapy. In our recent work, we analyzed data of patients with EGFR-mutant adenocarcinoma from January 2009. The number of patients investigated was 446, among them 44 cases were positive for EGFR mutation. The ratio of positive cases was 9.86 % that is lower than the average mutation rate in Europe and much lower than that found in Asia. The exon 19 deletion was detected in 61.4 % of the patients, while L858R point mutation in exon 21 was observed in 34.1 % of them. In one subject, both exon 19 and 21 mutations were present simultaneously. A rare mutation located in exon 21 was found in another patient. TKI therapy was conducted in 38 patients. The disease control rate by TKI therapy was 85.7 %; primary resistance was documented in five subjects. Non-smoking patients with EGFR mutant adenocarcinoma had the highest benefit from TKI treatment. Our data support the recommendation that EGFR mutation status should be defined in all cases of locally advanced or metastatic lung adenocarcinoma.

Molecular and cytogenomic profiling of hepatic adenocarcinoma expressing inhibinA, a mimicker of neuroendocrine tumors: proposal to reclassify as "cholangioblastic variant of intrahepatic cholangiocarcinoma".

PubMed

Braxton, David R; Saxe, Debra; Damjanov, Nevena; Stashek, Kristen; Shroff, Stuti; Morrissette, Jennifer D; Tondon, Rashmi; Furth, Emma E

2017-04-01

Only a single case report exists in the literature of hepatic adenocarcinoma expressing InhibinA in a young woman, in which the authors proposed it to be a rare variant of intrahepatic cholangiocarcinoma (iCCA). We present novel molecular and histologic findings in our series of three cases occurring in young women and show these tumors may mimic well-differentiated neuroendocrine tumors (NET). Immunohistochemical (IHC) profiling was performed along with a next-generation sequencing (NGS) 47-gene solid tumor panel, and cytogenomic profiling via single-nucleotide polypmorphism microarray. IHC for inhibinA, chromogranin A (ChrA), and synaptophysin (Syn) was surveyed in liver tumors and in fetal liver. Two of the three patients recurred with metastatic disease with two confirmed deaths. Histological patterns present in the tumors included solid, trabecular, organoid, microcystic, and blastemal-like. IHC was positive for cytokeratin 7 in 3/3, cytokeratin 19 in 3/3, inhibinA in 3/3, ChrA in 3/3, Syn in 3/3, Sox9 in 2/3 and HepPar1 in 0/3. NGS was negative for pathogenic mutations. Recurrent cytogenomic abnormalities included gain of 17q, and loss of 6q. InhibinA was strong and diffusely expressed in 0/10 (0%) iCCA, 0/15 (0%) hepatocellular carcinomas (HCC), in the biliary component of 1/4 (25%) combined HCC-iCCA, 0/4 hepatoblastomas, 1/8 (13%) metastatic NET, and in 1/8 fetal liver tissues. We propose a classification of "cholangioblastic variant of intrahepatic cholangiocarcinoma" and molecular pathogenesis for this rare malignancy. Accurate identification on core biopsy is crucial for clinical management as it may mimic neuroendocrine neoplasms. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic impact of early nutritional support in patients affected by locally advanced and metastatic pancreatic ductal adenocarcinoma undergoing chemotherapy.

PubMed

Trestini, Ilaria; Carbognin, Luisa; Sperduti, Isabella; Bonaiuto, Clelia; Auriemma, Alessandra; Melisi, Davide; Salvatore, Lisa; Bria, Emilio; Tortora, Giampaolo

2018-05-01

The aim of this analysis was to determine the risk of malnutrition and the prognostic value of nutritional intervention in patients affected by pancreatic ductal adenocarcinoma (PDAC) undergoing chemotherapy. Clinical-pathological and nutritional data were correlated with overall survival (OS) using a Cox model. Nutritional status was determined by Malnutrition Universal Screening Tool (MUST), body mass index, weight loss in the past 6 months, presence of nutrition-related symptoms, and current energy intake. Nutritional intervention included appropriate individual dietary counseling. Data from 109 patients were gathered (median age 63 years). The majority of patients (64.2%) presented a MUST value of ≥ 2, corresponding to a high risk of malnutrition. At multivariate analysis for OS in locally advanced and metastatic PDAC patients, the time between the diagnosis and the nutritional intervention (HR 2.22, p = 0.017), the performance status (HR 1.38, p = 0.075), the surgery of the primary (HR 5.89, p = 0.005), and the response to the first line (HR 5.9, p = 0.03) were independent significant predictors of outcome. Furthermore, a weight gain > 2% from the baseline weight was correlated with the time between the diagnosis and the nutritional intervention (p = 0.021): in patients receiving a nutritional support within 3 months from diagnosis, a 2% weight gain was associated with a 2-year OS benefit (50.3% vs. 33.0%, p = 0.04). This analysis suggests that the early nutritional support may contribute to influence the prognosis of patients affected by advanced PDAC undergoing chemotherapy.

Evidence for circulating cancer stem-like cells and epithelial-mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy.

PubMed

Mirza, Sheefa; Jain, Nayan; Rawal, Rakesh

2017-03-01

Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(-) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

Identification and survival outcomes of a cohort of patients with cancer of unknown primary in Ontario, Canada.

PubMed

Kim, Chong S; Hannouf, Malek B; Sarma, Sisira; Rodrigues, George B; Rogan, Peter K; Mahmud, Salaheddin M; Winquist, Eric; Brackstone, Muriel; Zaric, Gregory S

2015-11-01

Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma.

PubMed

Urie, Bridget K; Russell, Duncan S; Kisseberth, William C; London, Cheryl A

2012-05-25

Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma

PubMed Central

2012-01-01

Background Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. Results mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Conclusions Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib’s activity. PMID:22630170

Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

PubMed

Kälsch, Julia; Padden, Juliet; Bertram, Stefanie; Pott, Leona L; Reis, Henning; Westerwick, Daniela; Schaefer, Christoph M; Sowa, Jan-P; Möllmann, Dorothe; Fingas, Christian; Dechȇne, Alexander; Sitek, Barbara; Eisenacher, Martin; Canbay, Ali; Ahrens, Maike; Baba, Hideo A

2017-05-01

Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

Huntingtin-Interacting Protein-1 Is an Early-Stage Prognostic Biomarker of Lung Adenocarcinoma and Suppresses Metastasis via Akt-mediated Epithelial-Mesenchymal Transition.

PubMed

Hsu, Che-Yu; Lin, Cheng-Han; Jan, Yi-Hua; Su, Chia-Yi; Yao, Yun-Chin; Cheng, Hui-Chuan; Hsu, Tai-I; Wang, Po-Shun; Su, Wen-Pin; Yang, Chih-Jen; Huang, Ming-Shyan; Calkins, Marcus J; Hsiao, Michael; Lu, Pei-Jung

2016-04-15

Non-small cell lung cancer (NSCLC) carries a poor survival rate mainly because of metastasis. However, the molecular mechanisms that govern NSCLC metastasis have not been described. Because huntingtin-interacting protein-1 (HIP1) is known to play a role in tumorigenesis, we tested the involvement of HIP1 in NSCLC progression and metastasis. HIP1 expression was measured in human NSCLC tumors, and correlation with survival outcome was evaluated. Furthermore, we investigated the ability of HIP1 to suppress metastasis. The molecular mechanism by which HIP1 contributes to suppress metastasis was investigated. We used tissue arrays containing samples from 121 patients with NSCLC to analyze HIP1 expression by immunohistochemistry. To investigate the role of HIP1 expression on metastasis, we evaluated cellular mobility, migration, and invasion using lung adenocarcinoma (AdCA) cells with modified HIP1 expression levels. The human disease mouse models with the same cells were applied to evaluate the HIP1 suppressing metastasis and its mechanism in vivo. HIP1 expression in AdCA progression was found to be an early-stage prognostic biomarker, with low expression correlated to poor prognosis. We also found HIP1 to be a metastatic suppressor in AdCA. HIP1 significantly repressed the mobility of lung cancer cells in vitro and in vivo and regulated the epithelial-mesenchymal transition by repressing AKT/glycogen synthase kinase-3β/β-catenin signaling. HIP1 serves as an early-stage prognostic biomarker and a metastatic suppressor. Reduced expression during AdCA progression can relieve HIP1 suppression of Akt-mediated epithelial-mesenchymal transition and thereby lead to development of late metastases and poor prognosis.

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

PubMed

Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

2013-12-01

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.

PubMed

Miura, Nami; Kamita, Masahiro; Kakuya, Takanori; Fujiwara, Yutaka; Tsuta, Koji; Shiraishi, Hideaki; Takeshita, Fumitaka; Ochiya, Takahiro; Shoji, Hirokazu; Huang, Wilber; Ohe, Yuichiro; Yamada, Tesshi; Honda, Kazufumi

2016-05-31

Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (-)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (-). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells.

RNA sequencing enables systematic identification of platelet transcriptomic alterations in NSCLC patients.

PubMed

Zhang, Qun; Hu, Huan; Liu, Hongda; Jin, Jiajia; Zhu, Peiyuan; Wang, Shujun; Shen, Kaikai; Hu, Yangbo; Li, Zhou; Zhan, Ping; Zhu, Suhua; Fan, Hang; Zhang, Jianya; Lv, Tangfeng; Song, Yong

2018-05-29

Platelets are implicated as key players in the metastatic dissemination of tumor cells. Previous evidence demonstrated platelets retained cytoplasmic RNAs with physiologically activity, splicing pre-mRNA to mRNA and translating into functional proteins in response to external stimulation. Recently, platelets gene profile of healthy or diseased individuals were characterized with the help of RNA sequencing (RNA-Seq) in some studies, leading to new insights into the mechanisms underlying disease pathogenesis. In this study, we performed RNA-seq in platelets from 7 healthy individuals and 15 non-small cell lung cancer (NSCLC) patients. Our data revealed a subset of near universal differently expressed gene (DEG) profiles in platelets of metastatic NSCLC compared to healthy individuals, including 626 up-regulated RNAs (mRNAs and ncRNAs) and 1497 down-regulated genes. The significant over-expressed genes showed enrichment in focal adhesion, platelets activation, gap junction and adherens junction pathways. The DEGs also included previously reported tumor-related genes such as PDGFR, VEGF, EGF, etc., verifying the consistence and significance of platelet RNA-Seq in oncology study. We also validated several up-regulated DEGs involved in tumor cell-induced platelet aggregation (TCIPA) and tumorigenesis. Additionally, transcriptomic comparison analyses of NSCLC subgroups were conducted. Between non-metastatic and metastatic NSCLC patients, 526 platelet DEGs were identified with the most altered expression. The outcomes from subgroup analysis between lung adenocarcinoma and lung squamous cell carcinoma demonstrated the diagnostic potential of platelet RNA-Seq on distinguishing tumor histological types. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype.

PubMed

Monterisi, Simona; Lo Riso, Pietro; Russo, Karin; Bertalot, Giovanni; Vecchi, Manuela; Testa, Giuseppe; Di Fiore, Pier Paolo; Bianchi, Fabrizio

2018-03-26

HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

NASA Astrophysics Data System (ADS)

Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth

2016-11-01

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

A 63-year-old man with peripheral facial nerve paralysis and a pulmonary lesion.

PubMed

Yserbyt, J; Wilms, G; Lievens, Y; Nackaerts, K

2009-01-01

Occasionally, malignant neoplasms may cause peripheral facial nerve paralysis as a presenting symptom. A 63-year-old man was referred to the Emergency Department because of a peripheral facial nerve paralysis, lasting for 10 days. Initial diagnostic examinations revealed no apparent cause for this facial nerve paralysis. Chest X-ray, however, showed a suspicious tumoural mass, located in the right hilar region, as confirmed by CAT scan. The diagnosis of an advanced stage lung adenocarcinoma was finally confirmed by bronchial biopsy. MRI scanning showed diffuse brain metastases and revealed a pontine lesion as the most probable underlying cause of this case of peripheral facial nerve paralysis. Platin-based palliative chemotherapy was given, after an initial pancranial irradiation. According to the MRI findings, the pontine lesion was responsible for the peripheral facial nerve paralysis, as an initial presenting symptom in this case of lung adenocarcinoma. This clinical case of a peripheral facial nerve paralysis was caused by a pontine brain metastasis and illustrates a rather rare presenting symptom of metastatic lung cancer.

Caecal cancer presenting as leg erythema and a lung opacity.

PubMed

Das, Archik; Hureibi, Khalid; Tayyab, Muhammad; McCullough, Peter

2017-09-07

Necrotising infection of the lower limb is a rare presentation for colorectal malignancy. We report a case of a perforated caecal adenocarcinoma presenting with right leg erythema, pain and swelling in the presence of a right lower lobe lung opacity. Following initial debridement and washout, CT imaging demonstrated a thickened terminal ileum, caecum and appendix, in keeping with primary malignancy. This fed the right-sided lower limb sepsis tracking down from the medial aspect of the psoas muscle to give rise to the multiloculated collection seen in the adductor compartment. The lung lesion measured 16 mm and was metastatic. The patient was successfully managed with a subtotal colectomy and an end ileostomy. The biopsy confirmed an adenocarcinoma (T4N1M1). We highlight the importance of perforated colonic carcinoma as a leading differential for lower limb abscesses. Suspicions should be raised further if accompanied by rounded opacifications on plain film radiography of the lungs. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Unique presentation of giant metastatic microcystic serous adenocarcinoma of the pancreas.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, Kn Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures.

Unique Presentation of Giant Metastatic Microcystic Serous Adenocarcinoma of the Pancreas

PubMed Central

Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, KN Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures. PMID:24782930

Comparative label-free LC-MS/MS analysis of colorectal adenocarcinoma and metastatic cells treated with 5-fluorouracil.

PubMed

Bauer, Kerry M; Lambert, Paul A; Hummon, Amanda B

2012-06-01

A label-free mass spectrometric strategy was used to examine the effect of 5-fluorouracil (5-FU) on the primary and metastatic colon carcinoma cell lines, SW480 and SW620, with and without treatment. 5-FU is the most common chemotherapeutic treatment for colon cancer. Pooled biological replicates were analyzed by nanoLC-MS/MS and protein quantification was determined via spectral counting. Phenotypic and proteomic changes were evident and often similar in both cell lines. The SW620 cells were more resistant to 5-FU treatment, with an IC(50) 2.7-fold higher than that for SW480. In addition, both cell lines showed pronounced abundance changes in pathways relating to antioxidative stress response and cell adhesion remodeling due to 5-FU treatment. For example, the detoxification enzyme NQO1 was increased with treatment in both cell lines, while disparate members of the peroxiredoxin family, PRDX2 or PRDX5 and PRDX6, were elevated with 5-FU exposure in either SW480 or SW620, respectively. Cell adhesion-associated proteins CTNNB1 and RhoA showed decreased expression with 5-FU treatment in both cell lines. The differential quantitative response in the proteomes of these patient-matched cell lines to drug treatment underscores the subtle molecular differences separating primary and metastatic cancer cells. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.

PubMed

Ansari, Daniel; Urey, Carlos; Gundewar, Chinmay; Bauden, Monika Posaric; Andersson, Roland

2013-10-01

OBJECTIVE. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. MATERIAL AND METHODS. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. RESULTS. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.

Pancreatic cancer ascites xenograft–an expeditious model mirroring advanced therapeutic resistant disease

PubMed Central

Schvimer, Michael; Atias, Dikla; Halperin, Sharon; Buzhor, Ella; Raitses-Gurevich, Maria; Cohen, Keren; Pri-Chen, Sara; Wilson, Julie; Denroche, Robert E.; Lungu, Ilinca; Bartlett, John M.S.; Mbabaali, Faridah; Yarden, Yosef; Nataraj, Nishanth Belugali; Gallinger, Steven; Berger, Raanan

2017-01-01

Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations. PMID:28489577

Loss of Canonical Smad4 Signaling Promotes KRAS Driven Malignant Transformation of Human Pancreatic Duct Epithelial Cells and Metastasis

PubMed Central

Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Wang, Dennis; To, Christine; Ibrahimov, Emin; Tsao, Ming-Sound

2013-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell line model. Marked Smad4 downregulation by shRNA in KRAS G12V expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR) cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells. PMID:24386371

High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

PubMed

Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis.

PubMed

Kim, Green; Kim, Tae-Hyoun; Hwang, Eun-Ha; Chang, Kyu-Tae; Hong, Jung Joo; Park, Jong-Hwan

2017-07-01

Human gastric adenocarcinoma (AGS) is one of the most common types of malignant tumor and the third-leading cause of tumor-associated mortality worldwide. Withaferin A (WA), a steroidal lactone derived from Withania somnifera , exhibits antitumor activity in a variety of cancer models. However, to the best of our knowledge, the direct effect of WA on AGS cells has not previously been determined. The present study investigated the effects of WA on the proliferation and metastatic activity of AGS cells. WA exerted a dose-dependent cytotoxic effect on AGS cells. The effect was associated with cell cycle arrest at the G2/M phase and the expression of apoptotic proteins. Additionally, WA treatment resulted in a decrease in the migration and invasion ability of the AGS cells, as demonstrated using a wound healing assay and a Boyden chamber assay. These results indicate that WA directly inhibits the proliferation and metastatic activity of gastric cancer cells, and suggest that WA may be developed as a drug for the treatment of gastric cancer.

Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis

PubMed Central

Kim, Green; Kim, Tae-Hyoun; Hwang, Eun-Ha; Chang, Kyu-Tae; Hong, Jung Joo; Park, Jong-Hwan

2017-01-01

Human gastric adenocarcinoma (AGS) is one of the most common types of malignant tumor and the third-leading cause of tumor-associated mortality worldwide. Withaferin A (WA), a steroidal lactone derived from Withania somnifera, exhibits antitumor activity in a variety of cancer models. However, to the best of our knowledge, the direct effect of WA on AGS cells has not previously been determined. The present study investigated the effects of WA on the proliferation and metastatic activity of AGS cells. WA exerted a dose-dependent cytotoxic effect on AGS cells. The effect was associated with cell cycle arrest at the G2/M phase and the expression of apoptotic proteins. Additionally, WA treatment resulted in a decrease in the migration and invasion ability of the AGS cells, as demonstrated using a wound healing assay and a Boyden chamber assay. These results indicate that WA directly inhibits the proliferation and metastatic activity of gastric cancer cells, and suggest that WA may be developed as a drug for the treatment of gastric cancer. PMID:28693185

Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

PubMed Central

Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

2015-01-01

A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT. PMID:26170575

Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland.

PubMed

Takeyama, Hiroshi; Takahashi, Hiroyuki; Tabei, Isao; Fukuchi, Osamu; Nogi, Hiroko; Kinoshita, Satoki; Uchida, Ken; Morikawa, Toshiaki

2010-04-01

A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 x 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin-eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.

MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity

PubMed Central

Sharbeen, George; Youkhana, Janet; Mawson, Amanda; McCarroll, Joshua; Nunez, Andrea; Biankin, Andrew; Johns, Amber; Goldstein, David; Phillips, Phoebe

2017-01-01

Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread. PMID:27999205

Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer.

PubMed

Ray, P; Bhatti, R; Gadarowski, J; Bell, N; Nasruddin, S

1998-01-01

The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid.

PubMed Central

Nistér, M.; Enblad, P.; Bäckström, G.; Söderman, T.; Persson, L.; Heldin, C. H.; Westermark, B.

1994-01-01

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier. PMID:8180030

Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression

PubMed Central

Gibbons, Don L.; Lin, Wei; Creighton, Chad J.; Rizvi, Zain H.; Gregory, Philip A.; Goodall, Gregory J.; Thilaganathan, Nishan; Du, Liqin; Zhang, Yiqun; Pertsemlidis, Alexander; Kurie, Jonathan M.

2009-01-01

Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here, we address this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. Despite having widespread somatic genetic alterations, the metastasis-prone tumor cells retained a marked plasticity. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in three-dimensional culture that underwent epithelial-to-mesenchymal transition (EMT) following treatment with transforming growth factor-β or injection into syngeneic mice. This transition was entirely dependent on the microRNA (miR)-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize, and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that tumor cell metastasis is regulated by miR-200 expression, which changes in response to contextual extracellular cues. PMID:19759262

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

PubMed Central

Goddard, Erica T.; Fischer, Jacob; Schedin, Pepper

2016-01-01

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas. PMID:28060292

Prognostic impact of KRAS mutation subtypes in 677 patients with metastatic lung adenocarcinomas

PubMed Central

Yu, Helena A.; Sima, Camelia S.; Shen, Ronglai; Kass, Samantha; Gainor, Justin; Shaw, Alice; Hames, Megan; Iams, Wade; Aston, Jonathan; Lovly, Christine M.; Horn, Leora; Lydon, Christine; Oxnard, Geoffrey R.; Kris, Mark G.; Ladanyi, Marc; Riely, Gregory J.

2015-01-01

Background We previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared to patients with KRAS wild type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer. Methods We reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6 year time period. We evaluated the associations between KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient data set. Results Among 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p=0.99), smoking status (p=0.33) or when comparing specific amino acid substitutions (p=0.20). In our data set, patients with KRAS codon 13 mutant tumors (n=53) had shorter overall survival compared to patients with codon 12 mutant tumors (n=624)( 1.1 vs 1.3 years, respectively, p=0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex and smoking status (HR 1.52 95% CI 1.11-2.08, p=0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 vs 1.1 years respectively, p=0.41). Conclusions Among individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are apparent differences in outcome based on KRAS mutation subtype PMID:25415430

Lower tract neoplasm: Update of imaging evaluation.

PubMed

Hartman, Robert; Kawashima, Akira

2017-12-01

Cancers of the lower urinary tract can arise from the bladder, urachus or urethra. Urothelial carcinoma of the bladder (UCB) is the most common of these. The presentation of bladder, urachal and urethral cancers can differ but many result in hematuria as an initial indication. The diagnosis and staging of these cancers often necessitate radiologic imaging often in the form of cross-section CT urography or MR urography. The following article reviews the specific nature of lower tract cancers and their imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Prophylactic Dendritic Cell-Based Vaccines Efficiently Inhibit Metastases in Murine Metastatic Melanoma

PubMed Central

Sennikov, Sergey V.; Vlassov, Valentin V.; Zenkova, Marina A.

2015-01-01

Recent data on the application of dendritic cells (DCs) as anti-tumor vaccines has shown their great potential in therapy and prophylaxis of cancer. Here we report on a comparison of two treatment schemes with DCs that display the models of prophylactic and therapeutic vaccination using three different experimental tumor models: namely, Krebs-2 adenocarcinoma (primary tumor), melanoma (B16, metastatic tumor without a primary node) and Lewis lung carcinoma (LLC, metastatic tumor with a primary node). Dendritic cells generated from bone marrow-derived DC precursors and loaded with lysate of tumor cells or transfected with the complexes of total tumor RNA with cationic liposomes were used for vaccination. Lipofectamine 2000 and liposomes consisting of helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and cationic lipid 2D3 (1,26-Bis(1,2-de-O-tetradecyl-rac-glycerol)-7,11,16,20-tetraazahexacosan tetrahydrocloride) were used for RNA transfection. It was shown that DCs loaded with tumor lysate were ineffective in contrast to tumor-derived RNA. Therapeutic vaccination with DCs loaded by lipoplexes RNA/Lipofectamine 2000 was the most efficient for treatment of non-metastatic Krebs-2, where a 1.9-fold tumor growth retardation was observed. Single prophylactic vaccination with DCs loaded by lipoplexes RNA/2D3 was the most efficient to treat highly aggressive metastatic tumors LLC and B16, where 4.7- and 10-fold suppression of the number of lung metastases was observed, respectively. Antimetastatic effect of single prophylactic DC vaccination in metastatic melanoma model was accompanied by the reductions in the levels of Th2-specific cytokines however the change of the levels of Th1/Th2/Th17 master regulators was not found. Failure of double prophylactic vaccination is explained by Th17-response polarization associated with autoimmune and pro-inflammatory reactions. In the case of therapeutic DC vaccine the polarization of Th1-response was found nevertheless the antimetastatic effect was less effective in comparison with prophylactic DC vaccine. PMID:26325576

Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4

PubMed Central

Miura, Nami; Kamita, Masahiro; Kakuya, Takanori; Fujiwara, Yutaka; Tsuta, Koji; Shiraishi, Hideaki; Takeshita, Fumitaka; Ochiya, Takahiro; Shoji, Hirokazu; Huang, Wilber; Ohe, Yuichiro; Yamada, Tesshi; Honda, Kazufumi

2016-01-01

Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ). In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (−)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (−). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells. PMID:27121206

A retrospective review of combination chemohormonal therapy as initial treatment for locally advanced or metastatic adenocarcinoma of the prostate.

PubMed

Amato, Robert J; Teh, Bin S; Henary, Haby; Khan, Muhammad; Saxena, Somyata

2009-01-01

Chemotherapy for hormone-refractory prostate cancer reduces PSA levels and enhances overall survival (OS), suggesting that administration in earlier disease stages may be beneficial. If expansion of an androgen-independent clone present during androgen deprivation mediates the transformation from an androgen-dependent to an androgen-independent phenotype, combination chemohormonal therapy would be effective initial treatment for locally advanced or metastatic prostate cancers. A retrospective review was conducted to evaluate results. Chemohormonal therapy outcomes were retrospectively evaluated in men with locally advanced or metastatic prostate cancer seen at our institution between January 2001 and February 2003. Chemotherapy consisted of three 8-week cycles (once weekly intravenous doxorubicin 20 mg/m(2) and thrice daily oral ketoconazole 400 mg in weeks 1, 3, and 5; once weekly intravenous docetaxel 35 mg/m(2) and thrice daily oral estramustine 280 mg in weeks 2, 4, and 6; and no therapy in weeks 7 and 8). Hormone therapy consisted of hormonal ablation during and after antiandrogen therapy after chemotherapy. Data for 31 men (median age, 63 years [range, 41-74 years]; white, 97% [30/31]) were reviewed. At 1 year, median PSA level had fallen 99.3% (range, 91.7%-99.9%) from a baseline value of 14.3 ng/ml (range, 1.9-497.9 ng/mL). Median time to progression was 34+ months (range, 14-68+ months). Median OS was 56+ months (range, 17-73+ months). Combination chemohormonal therapy for locally advanced or metastatic prostate cancer safely and effectively reduces PSA levels and increases OS. We are now testing this approach in a prospective, Phase II randomized clinical trial.

Decreased metastatic phenotype in cells resistant to Aminolevulinic acid-Photodynamic therapy

PubMed Central

Casas, Adriana; Di Venosa, Gabriela; Vanzulli, Silvia; Perotti, Christian; Mamome, Leandro; Rodriguez, Lorena; Simian, Marina; Juarranz, Angeles; Pontiggia, Osvaldo; Hasan, Tayyaba; Batlle, Alcira

2008-01-01

Photodynamic therapy (PDT) is a novel cancer treatment utilising a photosensitiser, visible light and oxygen. PDT often leaves a significant number of surviving tumour cells. In a previous work, we isolated and studied two PDT resistant clones derived from the mammary adenocarcinoma LM3 line (Int. J. Oncol. 29 (2006) 397–405). The isolated Clon 4 and Clon 8 exhibited a more fibroblastic, dendritic pattern and were larger than the parentals. In the present work we studied the metastatic potential of the two clones in comparison with LM3. We found that 100 % of LM3 invaded Matrigel, whereas only 19 ± 6 % and 24 ± 7 % of Clon 4 and Clon 8 cells invaded. In addition, 100% of LM3 cells migrated towards a chemotactic stimulus whereas 38 ± 8 % and 73 ± 10 % of Clones 4 and 8 respectively were able to migrate. In vivo, 100% of the LM3 injected mice developed spontaneous lung metastasis, whereas none of the Clon 8 did, and only one of the mice injected with Clon 4 did. No differences were found in the proteolytic enzyme profiles among the cells. Anchorage-dependent adhesion was also impaired in vivo in the resistant clones, evidenced by the lower tumour take, latency time and growth rates, although both clones showed in vitro higher binding to collagen I without overexpression of β1 integrin. This is the first work where the metastatic potential of cells surviving to PDT has been studied. PDT strongly affects the invasive phenotype of these cells, probably related to a higher binding to collagen. These findings may be crucial for the outcome of ALA-PDT of metastatic tumours, although further studies are needed to extrapolate the results to the clinic employing another photosensitisers and cell types. PMID:18662847

Chronic low dose ethanol induces an aggressive metastatic phenotype in TRAMP mice, which is counteracted by parthenolide.

PubMed

Morel, Katherine L; Ormsby, Rebecca J; Solly, Emma L; Tran, Linh N K; Sweeney, Christopher J; Klebe, Sonja; Cordes, Nils; Sykes, Pamela J

2018-06-23

Despite advances in prostate cancer therapy, dissemination and growth of metastases results in shortened survival. Here we examined the potential anti-cancer effect of the NF-κB inhibitor parthenolide (PTL) and its water soluble analogue dimethylaminoparthenolide (DMAPT) on tumour progression and metastasis in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model of prostate cancer. Six-week-old male TRAMP mice received PTL (40 mg/kg in 10% ethanol/saline), DMAPT (100 mg/kg in sterile water), or vehicle controls by oral gavage thrice weekly until palpable tumour formation. DMAPT treatment slowed normal tumour development in TRAMP mice, extending the time-to-palpable prostate tumour by 20%. PTL did not slow overall tumour development, while the ethanol/saline vehicle used to administer PTL unexpectedly induced an aggressive metastatic tumour phenotype. Chronic ethanol/saline vehicle upregulated expression of NF-κB, MMP2, integrin β1, collagen IV, and laminin, and induced vascular basement membrane degradation in primary prostate tumours, as well as increased metastatic spread to the lung and liver. All of these changes were largely prevented by co-administration with PTL. DMAPT (in water) reduced metastasis to below that of water-control. These data suggest that DMAPT has the potential to be used as a cancer preventive and anti-metastatic therapy for prostate cancer. Although low levels of ethanol consumption have not been shown to strongly correlate with prostate cancer epidemiology, these results would support a potential effect of chronic low dose ethanol on metastasis and the TRAMP model provides a useful system in which to further explore the mechanisms involved.

A case of cetuximab-related tumour lysis syndrome in metastatic rectal carcinoma

PubMed Central

Haroon, Muhammad; Kwong, Whye Yan; Cantwell, Brian; Walker, Frank

2010-01-01

A 60-year-old man was diagnosed with a moderately differentiated adenocarcinoma in November 2006. The computed tomography (CT), magnetic resonance imaging (MRI) and whole-body positron emission tomography–CT (PET–CT) scan showed the presence of multiple liver metastases which were confined to its right lobe. He had the first session of a combined therapy with cetuximab and 5-fluorouracil (5-FU) in March 2009; however, soon afterwards, he presented with the symptoms, signs and biochemistry suggestive of tumour lysis syndrome. Our unusual case highlights that tumour lysis syndrome can also develop in ‘low risk’ category tumours, and that clinicians should be vigilant in identifying at-risk patients. PMID:28657052

Immune mediated colitis caused by lung cancer treatment with atezolizumab.

PubMed

González Vázquez, Santiago; de la Riva Onandía, Susana; Echeveste, José Ignacio; Muñoz Navas, Miguel

2017-12-01

Atezolizumab is an IgG1 isotype monoclonal antibody against the protein programmed cell death-ligand 1 (PD- L1). PD-L1 may be highly expressed in some tumors and is believed to inhibit immune cells that recognize and attack tumor cells. Inhibition of PD-L1 can remove its inhibitory effect and provoke an anti-tumor response. In October 2016, the Food and Drugs Administration (FDA) approved atezolizumab for the treatment of patients with metastatic non-small cell lung cancer after disease progression during or following platinum based chemotherapy. We present the case of a 43-year-old male with stage IV lung adenocarcinoma in progression, despite standard chemotherapy.

Percutaneous ablation of pancreatic cancer

PubMed Central

D’Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

2016-01-01

Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review. PMID:27956791

Predicting soil water content at - 33 kPa by pedotransfer functions in stoniness 1 soils in northeast Venezuela.

PubMed

Pineda, M C; Viloria, J; Martínez-Casasnovas, J A; Valera, A; Lobo, D; Timm, L C; Pires, L F; Gabriels, D

2018-02-22

Soil water content is a key property in the study of water available for plants, infiltration, drainage, hydraulic conductivity, irrigation, plant water stress and solute movement. However, its measurement consumes time and, in the case of stony soils, the presence of stones difficult to determinate the water content. An alternative is the use of pedotransfer functions (PTFs), as models to predict these properties from readily available data. The present work shows a comparison of different widely used PTFs to estimate water content at-33 kPa (WR -33kPa ) in high stoniness soils. The work was carried out in the Caramacate River, an area of high interest because the frequent landslides worsen the quality of drinking water. The performance of all evaluated PTFs was compared with a PTF generated for the study area. Results showed that the Urach's PTF presented the best performance in relation to the others and could be used to estimate WR -33kPa in soils of Caramacate River basin. The calculated PTFs had a R 2 of 0.65. This was slightly higher than the R 2 of the Urach's PTF. The inclusion of the rock fragment volume could have the better results. The weak performance of the other PTFs could be related to the fact that the mountain soils of the basin are rich in 2:1 clay and high stoniness, which were not used as independent variables for PTFs to estimate the WR -33kPa .

Cystic mucinous adenocarcinoma of the lung: a case report

PubMed Central

2011-01-01

Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung, We underline the difficulty of the clinical pre-operative diagnosis of this cystic neoplasia radiologically mimicking a hydatid cyst, and we report the negative TTF1 immunostaining potentially misleading in the differential diagnosis with metastatic mucinous carcinomas. Finallly, we evidence the presence of a pre-existing mucinous benign lesion suggesting early and complete resection of benign appearing lung cysts because they can undergo malignant transformation if left untreated or they can already harbor foci of invasive carcinoma at the time of the presentation. Even if a good prognosis, better than in other lung carcinomas, with no recurrrence or metastasis after complete surgical exicision, has been reported for cystic mucinous cystoadenocarcinomas, the follow-up showed an aggressive biological behaviour, with the early onset of metastasis, in keeping with P53 positive immunostaining and high Ki-67 proliferation index. PMID:21970610

A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary

PubMed Central

Shiono, Saori; Saito, Tsuyoshi; Fujii, Hiroaki; Arakawa, Atsushi; Nakamura, Takanori; Yao, Takashi

2014-01-01

We report a case of a 44-year-old woman with bilateral ovarian carcinoma that had metastasized from the colon and mimicked primary mucinous cystadenocarcinoma. Macroscopically, both ovarian tumors were large, multiloculated cystic masses with abundant mucinous content. Histologically, they were lined with mucinous epithelium with mild to moderate nuclear atypia and showed stromal invasion and surface involvement. At first, the tumors were diagnosed as bilateral primary ovarian mucinous cystadenocarcinomas. However, three months after surgery, a large villous tumor was discovered in the ascending colon by colonoscopic examination and was surgically resected. Histologically, the colonic tumor was a villous adenomatous tumor with invasive components of mucinous adenocarcinoma composed of well-differentiated adenocarcinoma and exhibited abundant extracellular mucin production. As a villous adenomatous component was present in the mucosal area, the colonic tumor was considered a primary tumor. Therefore, the original diagnosis of bilateral ovarian tumors was revised for consistent with metastasis from the colon carcinoma, in line with the findings of immunohistochemistry and loss of heterozygosity analysis. This case highlights the importance of considering the possibility of metastatic tumors from the gastrointestinal tract in the diagnosis of mucinous ovarian tumors. PMID:24427362

The sebaceous gland antigen defined by the OM-1 monoclonal antibody is expressed at high density on the surface of ovarian carcinoma cells.

PubMed

de Kretser, T A; Thorne, H J; Jacobs, D J; Jose, D G

1985-09-01

A monoclonal antibody, designated OM-1, was raised against ovarian serous papillary cystadenocarcinoma (stage IV) cells. This antibody was found to react strongly with primary and metastatic ovarian serous cystadenocarcinomas and endometrioid carcinomas but the antigen detected was either absent or at very low levels in ovarian mucinous adenocarcinomas, clear cell carcinomas, benign serous and mucinous cystadenomas and Brenner tumours. The OM-1 antibody gave no detectable reaction with 93 other human tumours, including examples of breast and colon adenocarcinomas. In normal tissues the OM-1 antibody reacted with normal sebaceous gland cells, lung type II pneumocytes and placental syncytial trophoblasts. In the normal ovary OM-1 reactivity was confined to extremely weak staining of the surface epithelium. No reaction with any other ovarian cell type could be detected. No evidence of reaction with other normal cell populations present in 24 adult and seven foetal tissues was found. The antigen detected is compared with other ovarian tumour-associated antigens. The OM-1 antibody is likely to prove of value in the detection and diagnosis of ovarian carcinoma.

[Clear cells cervical adenocarcinoma in a girl no exposed to dietiletilbestrol].

PubMed

Romero-Durán, Elizabeth; Chávez-Bravo, Neyda Cecilia; García-Rodríguez, Antonio Severo

2012-01-01

the clear cell adenocarcinoma (CCA) in cervix is a rare disease. It represents only 2 to 7 % of whole adecocarcinomas of cervix. Its histological pattern seems identical to their counterparts elsewhere in the female genital tract, including the vagina, endometrial and ovary. The CCA is constituted by cells with a clear cytoplasm in tack that are arranged in a solid pattern, tubu-locystic, papillary, or mixed. an eleven year old girl with sporadic and intermittent transvaginal bleeding, and who felt in severe anemia due to hiperpolimenorrea treated with athinyl estradiol deso-gestrel was attended. She had not history of exposition in utero to diethyletilbestrol. Hysteroscopy showed an ectocervical exophytic lesion in a barrel of 7 × 3 × 3 cm, located predominantly in the posterior lip. A frozen section of the lesion was reported as a poorly differentiated malignant tumor compatible with cervical carcinoma. She underwent to simple trachelectomy. diagnostic difficulty was the age of the patient and the lack exposition in utero to DES, the differential diagnosis included the age group tumors and rhabdomyosarcoma botryoides and extragonadal endodermic origen with papillary and reticular pattern. Another was a metastatic CCA.

Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)

PubMed Central

Uccello, M.; Moschetta, M.; Mak, G.; Alam, T.; Henriquez, C. Murias; Arkenau, H.-T.

2018-01-01

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm. PMID:29507500

BAG3 increases the invasiveness of uterine corpus carcinoma cells by suppressing miR-29b and enhancing MMP2 expression.

PubMed

Habata, Shutaro; Iwasaki, Masahiro; Sugio, Asuka; Suzuki, Miwa; Tamate, Masato; Satohisa, Seiro; Tanaka, Ryoichi; Saito, Tsuyoshi

2015-05-01

Approximately 30% of uterine corpus carcinomas are diagnosed at an advanced stage and have a poor prognosis. Our previous study indicated that BCL2-associated athanogene 3 (BAG3) enhances matrix metalloproteinase-2 (MMP2) expression and binds to MMP2 to positively regulate the process of cell invasion in ovarian cancer cells. Recently, altered miRNA expression patterns were observed in several groups of patients with endometrial cancers. One of the altered miRNAs, miR-29b, reportedly reduces tumor invasiveness by suppressing MMP2 expression. Our aim in the present study was to examine the relationships among BAG3, miR-29b and MMP2 in endometrioid adenocarcinoma cells. We found that BAG3 suppresses miR-29b expression and enhances MMP2 expression, which in turn increases cell motility and invasiveness. Moreover, restoration of miR-29b through BAG3 knockdown reduced MMP2 expression, as well as cell motility and invasiveness. Collectively, our findings indicate that BAG3 enhances MMP2 expression by suppressing miR-29b, thereby increasing the metastatic potential of endometrioid adenocarcinomas.

Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

PubMed Central

Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A.; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O.

2017-01-01

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma. PMID:28620146

Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model.

PubMed

Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O

2017-07-04

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

Tumours of the female genital tract

PubMed Central

McEntee, Kenneth; Nielsen, Svend W.

1976-01-01

Tumours of the female tubular genital tract are comparatively rare, with the exception of leiomyomas in cows and bitches, uterine carcinomas and vaginal fibropapillomas in cows, and transmissible venereal tumours in bitches. Uterine adenocarcinomas of cows are highly scirrhous, often causing minimal gross lesions that remain undetected until metastatic lesions in pelvic nodes and lungs are found. Cats and bitches also develop uterine carcinomas, but less frequently than cows; when present, they are predominantly discrete masses of well differentiated, non-sclerosing adenocarcinoma. Fibropapillomas are caused by the virus of verrucca vulgaris and can be transmitted to the penis of the bull. Adenomyosis is not uncommon in the cat, cow, and bitch. There is a marked difference in the frequency with which cervical carcinomas occur in man compared with other mammals; in the latter we could find no instance of an unequivocal primary cervical carcinoma. There are a few reports describing invasive carcinomas involving the cervix, but invasion from either a uterine or a vaginal carcinoma could not be ruled out. ImagesFig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12Fig. 1Fig. 2Fig. 3Fig. 4 PMID:1086152

African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression

PubMed Central

Mukherjee, Angana; Jones, Jacqueline; Karanam, Balasubramanyam; Davis, Melissa; Jaynes, Jesse; Reams, R. Renee; Dean-Colomb, Windy; Yates, Clayton

2016-01-01

Kaiso, a bi-modal transcription factor, regulates gene expression, and is elevated in breast, prostate, and colon cancers. Depletion of Kaiso in other cancer types leads to a reduction in markers for the epithelial–mesenchymal transition (EMT) (Jones et al., 2014), however its clinical implications in pancreatic ductal adenocarcinoma (PDCA) have not been widely explored. PDCA is rarely detected at an early stage but is characterized by rapid progression and invasiveness. We now report the significance of the subcellular localization of Kaiso in PDCAs from African Americans. Kaiso expression is higher in the cytoplasm of invasive and metastatic pancreatic cancers. In males, cytoplasmic expression of Kaiso correlates with cancer grade and lymph node positivity. In male and female patients, cytoplasmic Kaiso expression correlates with invasiveness. Also, nuclear expression of Kaiso increases with increased invasiveness and lymph node positivity. Further, analysis of the largest PDCA dataset available on ONCOMINE shows that as Kaiso increases, there is an overall increase in Zeb1, which is the inverse for E-cadherin. Hence, these findings suggest a role for Kaiso in the progression of PDCAs, involving the EMT markers, E-cadherin and Zeb1. PMID:27424525

Desmoplastic small round cell tumor with sphere-like clusters mimicking adenocarcinoma.

PubMed

Hattori, Yukinori; Yoshida, Akihiko; Sasaki, Naoshi; Shibuki, Yasuo; Tamura, Kenji; Tsuta, Koji

2015-03-01

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere-like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients. © 2014 Wiley Periodicals, Inc.

[A Case of Sigmoid Colon Cancer with Metastasis to the Uterus].

PubMed

Tokoro, Yukinari; Tonooka, Toru; Souda, Hiroaki; Takiguchi, Nobuhiro; Chibana, Tomofumi; Kobayashi, Ryosuke; Arimitsu, Hidehito; Yanagibashi, Hiroo; Chou, Akihiro; Ikeda, Atsushi; Nabeya, Nobuhiro; Kainuma, Osamu; Yamamoto, Hiroshi; Nagata, Matsuo

2015-11-01

A 65-year-old woman complaining of fetor ex vagina was diagnosed with endometrial adenocarcinoma of the uterus based on the pathological findings of an endometrial biopsy. Sigmoid colon cancer was found on a pre-operative CT scan. Diagnosis of double cancer was made and we performed sigmoidectomy and panhysterectomy with associated resection of both adnexa. Histopathological examination found that the tumor accounted for almost all of the uterine mucosa and over half of the muscular layer. Immunostaining showed CK7 (-), CK20 (+), CDX2 (+), ER (-), and PgR (-), and we diagnosed it as a metastasis to the uterus of the sigmoid colon cancer. The pathological diagnosis was a moderately differentiated adenocarcinoma, pT4b (SI: urinary bladder), pN0 (0/12), H0, P1,M1a (uterus), pStage Ⅳ. As adjuvant chemotherapy, she was administered XELOX for 6 months. Although colorectal cancer rarely metastasizes to the uterus, due to the increase in the prevalence of colorectal cancer, it may be also increase. To choose the best treatment course, it is necessary to diagnose whether it is a primary uterine cancer or a metastatic uterine cancer.

Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis.

PubMed

Yamagata, Hideo; Matsuzaki, Koichi; Mori, Shigeo; Yoshida, Katsunori; Tahashi, Yoshiya; Furukawa, Fukiko; Sekimoto, Go; Watanabe, Toshihiko; Uemura, Yoshiko; Sakaida, Noriko; Yoshioka, Kazuhiko; Kamiyama, Yasuo; Seki, Toshihito; Okazaki, Kazuichi

2005-01-01

Conversion of normal epithelial cells to tumors is associated with a shift in transforming growth factor-beta (TGF-beta) function: reduction of tumor suppressor activity and increase of oncogenic activity. However, specific mechanisms of this functional alteration during human colorectal carcinogenesis remain to be elucidated. TGF-beta signaling involves Smad2/3 phosphorylated at linker regions (pSmad2/3L) and COOH-terminal regions (pSmad2/3C). Using antibodies specific to each phosphorylation site, we herein showed that Smad2 and Smad3 were phosphorylated at COOH-terminal regions but not at linker regions in normal colorectal epithelial cells and that pSmad2/3C were located predominantly in their nuclei. However, the linker regions of Smad2 and Smad3 were phosphorylated in 31 sporadic colorectal adenocarcinomas. In particular, late-stage invasive and metastatic cancers typically showed a high degree of phosphorylation of Smad2/3L. Their extent of phosphorylation in 11 adenomas was intermediate between those in normal epithelial cells and adenocarcinomas. Whereas pSmad2L remained in the cytoplasm, pSmad3L was located exclusively in the nuclei of Ki-67-immunoreactive adenocarcinomas. In contrast, pSmad3C gradually decreased as the tumor stage progressed. Activated c-Jun NH(2)-terminal kinase in cancers could directly phosphorylate Smad2/3L. Although Mad homology 2 region sequencing in the Smad4 gene revealed a G/A substitution at codon 361 in one adenocarcinoma, the mutation did not correlate with phosphorylation. No mutations in the type II TGF-beta receptor and Smad2 genes were observed in the tumors. In conclusion, pSmad3C, which favors tumor suppressor activity of TGF-beta, was found to decrease, whereas c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence.

Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract.

PubMed

Hong, Jung Yong; Choi, Moon Ki; Uhm, Ji Eun; Park, Min Jae; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kim, Won Seog; Kang, Won Ki; Lee, Hyun Moo; Choi, Han Yong; Lim, Hoyeong

2009-01-01

Non-transitional cell carcinomas of the urothelial tract comprise 5-10% of urothelial cancers. Clinical information regarding the clinical behavior and chemotherapy outcome of non-transitional cell carcinomas of the urothelial tract are incomplete due to their rarity. The object of this study was to evaluate the clinical features and the efficacy of palliative chemotherapy in advanced non-transitional cell carcinomas of the urothelial tract. We analyzed the clinical records of 21 consecutive patients who received palliative chemotherapy for unresectable or metastatic non-transitional cell carcinomas of the urothelial tract between January 1995 and November 2007. All the 21 patients received first-line chemotherapy with platinum-based regimens which are known to be effective in transitional cell urothelial carcinomas. The median age of the patients was 57 years (range, 27-71 years). The primary sites of involvement were the bladder, urethra, urachus, and ureter in 43%, 29%, 19%, and 10% of the patients, respectively. Adenocarcinoma was the most common histological type (67%); squamous cell carcinoma and small cell carcinoma comprised 24 and 10% of the histologic types, respectively. With a median duration of follow-up of 32 months (range, 12-71 months), the median overall survival for all 21 patients from the day of first-line chemotherapy was 13 months (95% CI, 6.8-19.2). The expected 1-year survival rate was 50.6% (95% CI, 28.6-72.5). Univariate analysis showed a better median overall survival in patients with adenocarcinoma, compared to non-adenocarcinomas (47 vs. 10 months, P = 0.049). The median overall survival of patients who received platinum-based palliative chemotherapy for advanced non-transitional cell carcinomas was comparable to previous studies for patients with transitional cell carcinomas. Adenocarcinomas appear to have a favorable prognosis for the survival of the patients who received platinum-based chemotherapy for advanced non-transitional cell carcinomas.

HER2 Status in Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma for Entry to the TRIO-013/LOGiC Trial of Lapatinib.

PubMed

Press, Michael F; Ellis, Catherine E; Gagnon, Robert C; Grob, Tobias J; Buyse, Marc; Villalobos, Ivonne; Liang, Zhiyong; Wu, Shafei; Bang, Yung-Jue; Qin, Shu-Kui; Chung, Hyun Cheol; Xu, Jianming; Park, Joon Oh; Jeziorski, Krzysztof; Afenjar, Karen; Ma, Yanling; Estrada, Monica C; Robinson, Douglas M; Scherer, Stefan J; Sauter, Guido; Hecht, J Randolph; Slamon, Dennis J

2017-01-01

HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2 In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low. Mol Cancer Ther; 16(1); 228-38. ©2016 AACR. ©2016 American Association for Cancer Research.

Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.

PubMed

Hecht, J Randolph; Bang, Yung-Jue; Qin, Shukui K; Chung, Hyun C; Xu, Jianming M; Park, Joon O; Jeziorski, Krzysztof; Shparyk, Yaroslav; Hoff, Paulo M; Sobrero, Alberto; Salman, Pamela; Li, Jin; Protsenko, Svetlana A; Wainberg, Zev A; Buyse, Marc; Afenjar, Karen; Houé, Vincent; Garcia, Agathe; Kaneko, Tomomi; Huang, Yingjie; Khan-Wasti, Saba; Santillana, Sergio; Press, Michael F; Slamon, Dennis

2016-02-10

To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma. Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population. A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea. Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation. © 2015 by American Society of Clinical Oncology.

Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium.

PubMed

Steuer, Conor E; Behera, Madhusmita; Berry, Lynne; Kim, Sungjin; Rossi, Michael; Sica, Gabriel; Owonikoko, Taofeek K; Johnson, Bruce E; Kris, Mark G; Bunn, Paul A; Khuri, Fadlo R; Garon, Edward B; Ramalingam, Suresh S

2016-03-01

The discovery of oncogenic drivers has ushered in a new era for lung cancer, but the role of these mutations in different racial/ethnic minorities has been understudied. The Lung Cancer Mutation Consortium 1 (LCMC1) database was investigated to evaluate the frequency and impact of oncogenic drivers in lung adenocarcinomas in the racial/ethnic minority patient population. Patients with metastatic lung adenocarcinomas from 14 US sites were enrolled in the LCMC1. Tumor samples were collected from 2009 through 2012 with multiplex genotyping performed on 10 oncogenic drivers (KRAS, epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase (ALK) rearrangements, ERBB2 [formerly human epidermal growth factor receptor 2], BRAF, PIK3CA, MET amplification, NRAS, MEK1, and AKT1). Patients were classified as white, Asian, African American (AA), or Latino. The driver mutation frequency, the treatments, and the survival from diagnosis were determined. One thousand seven patients were included. Whites represented the majority (n = 838); there were 60 AAs, 48 Asians, and 28 Latinos. Asian patients had the highest rate of oncogenic drivers with 81% (n = 39), and they were followed by Latinos with 68% (n = 19), whites with 61% (n = 511), and AAs with 53% (n = 32). For AAs, the EGFR mutation frequency was 22%, the KRAS frequency was 17%, and the ALK frequency was 4%. Asian patients were most likely to receive targeted therapies (51% vs 27% for AAs). There were no significant differences in overall survival. Differences were observed in the prevalence of oncogenic drivers in lung adenocarcinomas and in subsequent treatments among racial groups. The lowest frequency of drivers was seen for AA patients; however, more than half of AA patients had a driver, and those treated with targeted therapy had outcomes similar to those of other races. Cancer 2016;122:766-772. © 2015 American Cancer Society. © 2015 American Cancer Society.

Mucosal colonization by metastatic carcinoma in the gastrointestinal tract: a potential mimic of primary neoplasia.

PubMed

Estrella, Jeannelyn S; Wu, Tsung-Teh; Rashid, Asif; Abraham, Susan C

2011-04-01

The gastrointestinal (GI) tract is a common site for both primary and metastatic carcinomas. Distinguishing the two can occasionally be difficult, particularly when metastatic tumor reaches the mucosal surface. Features that are typically used to make this distinction include the presence of an adenomatous precursor lesion, regional lymph node involvement, and gross configuration of the tumor. However, we recently encountered 2 index cases of metastatic carcinoma in the small intestine (1 from the colorectum and 1 of endocervical origin) that were initially misinterpreted as primary small bowel carcinomas because of apparent in situ growth in the mucosal surface resembling polypoid, adenomatous precursor lesions. We, therefore, studied 100 GI resections from 1987 to 2009 that were reported to show mucosal involvement by metastatic carcinoma, and compared the histologic features with a control group of 29 primary small bowel adenocarcinomas. Gross descriptions and histologic sections were evaluated for the following: (1) tumor spread along an intact basement membrane of villi/crypts (mucosal colonization), (2) resemblance to an adenoma/precursor lesion, (3) gross configuration of the tumor, (4) lymphovascular invasion, and (5) regional lymph node involvement in the metastatic site. Metastatic sites included the small intestine (n=74), colorectum (n=16), or both (n=10). Primary tumors were GI (n=55, with 47 from colorectum), gynecologic (n=28), pulmonary (n=8), genitourinary (n=6), head and neck (n=2), and breast (n=1). Overall, 42 (42%) of the metastases that reached the mucosal surface of the bowel showed at least focal mucosal colonization, 26% resembled a precursor adenoma, 62% had regional lymph node positivity, and only 24% cases showed a classic serosal-based configuration. In 4 cases (2 of GI origin and 2 of gynecologic origin), metastatic tumors were initially interpreted as new primaries by the pathologist (n=2) or clinicians (n=2). Metastatic carcinomas originating from the GI tract were significantly more likely to show mucosal colonization (60% vs. 20%, P<0.0001) and resemblance to a precursor lesion (45% vs. 2%, P<0.0001) than other primary tumors. In a comparison between 29 primary small bowel carcinomas and 41 metastatic colorectal carcinomas in the small bowel, metastatic tumors were distinguished by a higher prevalence of multiple lesions (0% vs. 39%, P<0.0001), whereas small bowel primaries were more likely to show high tumor grade (41% vs. 17%, P=0.03). There were no significant differences in the mean age (61.4 y vs. 60.9 y), number of male participants (69% vs. 56%), growth along basement membranes (62% vs. 63%), apparent precursor lesion (55% vs. 46%), lymphovascular invasion (69% vs. 73%), or lymph node positivity (68% vs. 37.5%, P=0.065). These results confirm that metastatic carcinomas involving the mucosal surface of the intestines frequently exhibit gross and histologic features, which mimic second primaries, especially when they originate from the GI tract. In situ growth and presence of an apparent adenoma cannot be taken as prima facie evidence of a primary neoplasm.

Label-Free Isolation and mRNA Detection of Circulating Tumor Cells from Patients with Metastatic Lung Cancer for Disease Diagnosis and Monitoring Therapeutic Efficacy.

PubMed

Wang, Jidong; Lu, Wenjing; Tang, Chuanhao; Liu, Yi; Sun, Jiashu; Mu, Xuan; Zhang, Lin; Dai, Bo; Li, Xiaoyan; Zhuo, Hailong; Jiang, Xingyu

2015-12-01

We develop an inertial-based microfluidic cell sorter combined with an integrated membrane filter, allowing for size-based, label-free, and high-efficiency separation and enrichment of circulating tumor cells (CTCs) in whole blood. The cell sorter is composed of a double spiral microchannel that hydrodynamically focuses and separates large CTCs from small blood cells. The focused CTCs with the equilibrium position around the midline of microchannel are further captured and enriched by a membrane filter (pore size of 8 μm) attached at the middle outlet. This integrated microfluidic device can process 1 mL of whole blood containing spiked tumor cells (A549, human lung adenocarcinoma epithelial cell line) within 15 min, with the capture efficiency of 74.4% at the concentration as low as tens of A549 cells per mL of whole blood. This microfluidic cell sorter is further adopted for isolation of CTCs from peripheral blood samples of patients with metastatic lung cancer. The immunostaining and CK-19 mRNA detection are applied for identification of captured CTCs, showing that our method can detect 90% of metastatic lung cancer patients before therapy, whereas the commercially used system can only detect 40% of the same patients. We also use the expression of CK-19 mRNA from captured CTCs as an indicator for monitoring the therapeutic efficiency, which correlates well with X-ray computed tomography (CT) assessment of the disease.

Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

PubMed

Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

2018-03-01

Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

Correlation of metastasis characteristics with prognosis in gastric mixed adenoneuroendocrine carcinoma

PubMed Central

Tang, Qiang; Zhou, Zili; Chen, Jinhuang; Di, Maojun; Ji, Jintong; Yuan, Wenzheng; Liu, Zhengyi; Wu, Liang; Zhang, Xudan; Li, Kang; Shu, Xiaogang

2017-01-01

Abstract Rationale: This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy. Patient concerns: The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena. Diagnosis: The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes. Interventions: The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness. Outcomes: The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation. Lessons: The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management. PMID:29390331

CT features of HER2-mutant lung adenocarcinomas.

PubMed

Sawan, Peter; Plodkowski, Andrew J; Li, Angela E; Li, Bob T; Drilon, Alexander; Capanu, Marinela; Ginsberg, Michelle S

2018-06-07

To describe the radiological phenotype of HER2-mutant lung cancers on CT at presentation. Eligible patients with lung adenocarcinomas with HER2 mutations were stage-matched with two control groups (EGFR- and KRAS-mutant groups). Evaluated CT features of the primary tumor included size, location, consistency, contour, presence of pleural tags and pleural retractions. Presence of pleural effusions, lung metastases, adenopathy, chest wall invasion, and were also recorded. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical features, respectively. One hundred and fifty-four patients were identified: 50 (33%) harbored HER2 mutations, 56 (36%) harbored KRAS mutations, and 48 (31%) harbored EGFR mutations. Compared with KRAS, HER2 tumors presented as smaller lesions (2.3 cm versus 2.9 cm, p = 0.005 for length; 1.6 cm versus 2.1 cm, p = 0.002 for width) with the presence of pleural tags (74% vs. 52%, p = 0.03), pleural retractions (58% vs. 39%, p = 0.006), ipsilateral hilar (36% vs. 16%, p = 0.03) and scalene/supraclavicular N3 adenopathy (24% vs. 7%, p = 0.03). Compared with EGFR, pleural retractions were more prevalent among the HER2 tumors (58% vs. 37%, p = 0.05). Lung adenocarcinomas with HER2 gene mutation exhibit an aggressive behavior manifesting by higher incidence of local invasion, compared to KRAS and EGFR mutant controls, and a nodal metastatic spread compared to KRAS-mutant control. This is the first radiogenomics study of HER2 mutations in lung cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer.

PubMed

Liu, Yong-Jun; Yan, Pei-Song; Li, Jun; Jia, Jing-Fen

2005-11-14

To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6, and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma, intraductal carcinoma of breast, and lung cancer. Using tissue microarray by immuhistochemical (IHC) staining and in situ hybridization (ISH), we examined the expression levels of nm23 mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6 in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer. The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P>0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P>0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P<0.01; r = -4.93, P<0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P<0.05; P<0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P<0.01; r = 5.04, P<0.01). CD44s and CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P<0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (c2 = 5.68, P<0.05). The expressional level of nm23 mRNA was closely related to the degree of cell differentiation (P<0.05) and lymph node metastasis (P<0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P>0.05). Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.

Detection of HER2 polymorphism and expression using circulating DNA and RNA as a tool in lung adenocarcinoma patients: a case control study.

PubMed

Mirza, Masroor; Javid, Jamsheed; Yadav, Prasant; Mohan, Anant; Ray, Prakash Chandra; Saxena, Alpana

2016-06-01

Circulating DNA and RNA is an important prognostic tool for noninvasive malignant disease detection and in disease prognosis. Study aimed to evaluate the possible prognostic role of HER2 (-3444C/T) promoter polymorphism and its mRNA expression in Lung adenocarcinoma patients using circulating DNA and RNA. One hundred newly diagnosed lung adenocarcinoma patients and 100 age and sex matched healthy controls were included and allele specific (AS) polymerase chain reaction (PCR) was used for genotyping and expression was analyzed by quantitative real time PCR. Overall survival of patients was analyzed by Kaplan-Meier method. We observed a statistically significant difference in the frequency of HER2 CC, CT, and CT genotype among lung adenocarcinoma cases vs. healthy controls (P=0.001). Compared to the CC genotype, OR 2.51 (1.4-4.51), 5.97 (1.17-30.41) and RR 1.56 (1.17-2.07), 2.83 (0.82-9.73) for heterozygous CT and homozygous TT genotypes suggesting possible dominant effect on risk of lung adenocarcinoma. Cases with CC genotype showed 9.29 fold increased mRNA expression while cases with heterozygous CT and homozygous TT genotype showed 16.26, 16.72 fold increased mRNA expression (P<0.0001). We observed 13.92 fold increased HER2mRNA expression Lung adenocarcinoma patients. Patients in different TNM stages showed significant difference in HER2 mRNA expression which was found to be significantly associated (P<0.0001). Patients with distant metastases and without distant metastases had 17.44 and 11.16 fold increased HER2 mRNA expression was also found to be significantly associated (P<0.0001). It was also observed that patients with pleural effusion and without pleural effusion showed significant difference in HER2 mRNA expression (P=0.03). We also analysed patients with CC, TT, CT (P=0.02) and CT + TT (P=0.008) genotype showed 15.8, 7.9, 9.5 and 7.9 months of overall median survival time and found to be significantly associated, respectively. Patients with >13 and ≤13 fold increased HER mRNA expression also showed 7.9 and 11.5 months of overall median survival time was also found to be significantly associated (P=0.01). Our work provides evidence that circulating DNA and RNA may be a potential prognostic tool in Lung adenocarcinoma patients. Promoter polymorphism of HER2 (-3444C/T) gene had significant impact on higher HER2 mRNA expression could be a predictive factor for patients' worse overall survival and metastatic behaviour.

Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

PubMed Central

Anota, Amélie; Mouillet, Guillaume; Trouilloud, Isabelle; Dupont-Gossart, Anne-Claire; Artru, Pascal; Lecomte, Thierry; Zaanan, Aziz; Gauthier, Mélanie; Fein, Francine; Dubreuil, Olivier; Paget-Bailly, Sophie; Taieb, Julien; Bonnetain, Franck

2015-01-01

Background A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study. Methods HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS. Results 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1. Conclusion Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics. Trial registration information Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM). PMID:26010884

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

PubMed

Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

2016-01-01

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis

PubMed Central

Sasada, Shinji; Izumo, Takehiro; Matsumoto, Yuji; Tsuchida, Takaaki

2016-01-01

Background Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Methods Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Results Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Conclusion Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic approach for malignant pleural diseases presenting with effusion. PMID:27880851

GLI1 inhibition promotes epithelial-to-mesenchymal transition in pancreatic cancer cells

PubMed Central

Joost, Simon; Almada, Luciana L.; Rohnalter, Verena; Holz, Philipp S.; Vrabel, Anne M.; Fernandez-Barrena, Maite G.; McWilliams, Robert R.; Krause, Michael; Fernandez-Zapico, Martin E.; Lauth, Matthias

2011-01-01

The Hedgehog (HH) pathway has been identified as an important deregulated signal transduction pathway in pancreatic ductal adenocarcinoma (PDAC), a cancer type characterized by a highly metastatic phenotype. In PDAC, the canonical HH pathway activity is restricted to the stromal compartment while HH signaling in the tumor cells is reduced as a consequence of constitutive KRAS activation. Here we report that in the tumor compartment of PDAC the HH pathway effector transcription factor GLI1 regulates epithelial differentiation. RNAi-mediated knockdown of GLI1 abolished characteristics of epithelial differentiation, increased cell motility and synergized with TGFβ to induce an epithelial-to-mesenchymal transition (EMT). Notably, EMT conversion in PDAC cells occurred in the absence of induction of SNAIL or SLUG, two canonical inducers of EMT in many other settings. Further mechanistic analysis revealed that GLI1 directly regulated the transcription of E-cadherin, a key determinant of epithelial tissue organization. Collectively, our findings identify GLI1 as an important positive regulator of epithelial differentiation, and they offer an explanation for how decreased levels of GLI1 are likely to contribute to the highly metastatic phenotype of PDAC. PMID:22086851

Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 integrin.

PubMed

Cao, Ying; Hoeppner, Luke H; Bach, Steven; E, Guangqi; Guo, Yan; Wang, Enfeng; Wu, Jianmin; Cowley, Mark J; Chang, David K; Waddell, Nicola; Grimmond, Sean M; Biankin, Andrew V; Daly, Roger J; Zhang, Xiaohui; Mukhopadhyay, Debabrata

2013-07-15

Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis. ©2013 AACR.

Cytomorphologic features of myxopapillary ependymoma: a review of 13 cases.

PubMed

Takei, Hidehiro; Kosarac, Ognjen; Powell, Suzanne Z

2009-01-01

To describe the cytologic features of myxopapillary ependymoma (MPE) on intraoperative smears, to analyze cytomorphologic parameters that may help in reaching the diagnosis and to discuss differential diagnosis. Touch imprint smears of 13 MPE cases were reviewed and graded semiquantitatively for 14 cytomorphologic parameters; cellularity, myxoid background, isolated/dispersed tumor cells, "hyaline globules (HGs)," fibrillary cytoplasmic processes, papillary structures, perivascular pseudorosettes, epithelioid tumor cells (ETCs), intracytoplasmic mucin, intranuclear inclusions, nuclear grooves, mitosis, cytologic atypia and hemosiderin-laden macrophages. Cytologic examination revealed variably cellular specimens composed of isolated and loosely aggregated tumor cells with round to oval or occasionally spindle-shaped nuclei; evenly distributed, finely granular chromatin; and fibrillary processes admixed with occasional ETCs. Most of the cases showed prominent fibrillary processes and occasional ETCs with at least a focal myxoid background. HGs and hemosiderin-laden macrophages were often seen. Papillary structure, a histologic hallmark of MPE, was rarely observed. Dual glial and epithelioid properties of tumor cells, well-known features of "regular" ependymomas, and a distinctive myxoid background with HGs strongly support a diagnosis of MPE and are of great help in excluding other mimics (e.g., other variants of ependymoma, metastatic mucinous adenocarcinoma, metastatic adenoid cystic carcinoma and chordoma).

Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells.

PubMed

Ricciardi, M; Zanotto, M; Malpeli, G; Bassi, G; Perbellini, O; Chilosi, M; Bifari, F; Krampera, M

2015-03-17

Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape. Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines. EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors. EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.

TGFβ signaling supports survival and metastasis of endometrial cancer cells

PubMed Central

Lei, XiuFen; Wang, Long; Yang, Junhua; Sun, Lu-Zhe

2009-01-01

The association of mutation of the transforming growth factor beta (TGFβ) type II receptor (RII) with microsatellite instability revealed a significant molecular mechanism of tumorigenesis and tumor progression in gastrointestinal carcinomas with DNA replication error. However, mutation of RII is rare in other types of carcinomas with microsatellite instability including endometrial adenocarcinoma suggesting that TGFβ receptor signaling may be necessary for tumor progression. To test this hypothesis, we abrogated TGFβ signaling with ectopic expression of a dominant-negative RII (DNRII) in human endometrial carcinoma HEC-1-A cells with microsatellite instability. Our study showed that over-expression of DNRII blocked the TGFβ signaling, inhibited anchorage-dependent and -independent growth, and stimulated apoptosis in vitro. Interestingly, the expression of DNRII expression showed little effect on tumor growth of subcutaneously inoculated cells in vivo. On the other hand, the DNRII cells showed more epithelial features whereas the control cells showed more mesenchymal features suggesting a reversal of autocrine TGFβ-induced epithelial–mesenchymal transition (EMT). Consistent with these findings, DNRII cells were much less migratory and invasive in vitro and metastatic in vivo than the control cells. Therefore, an intact TGFβ signaling pathway appears necessary for the metastatic phenotypes of this carcinoma model. PMID:20622970

Splenic abscess in cancer chemotherapy.

PubMed

Ismail, Essadi; El Barni, Rachid; Lahkim, Mohamed; Rokhsi, Redouane; Atmane, Elmehdi; El Fikri, Abdelghani; Bouchama, Rachid; Achour, Abdessamad; Zyani, Mohamed

2015-11-11

Splenic abcess is an uncommon complication for cancer treatment. It occurs more frequently in immunocompromised patients. They are characterized by high mortality. The classic triad (fever, pain of the left hypochondrium, and sensitive mass left) is only present in one-third of cases the clinical spectrum ranging from no symptoms to events such as fever, nausea, vomiting, weight loss, abdominal pain left, splenomegaly. Treatment options are limited, but must be discussed and adapted to the patient profile. We report the case of a 62-year-old Arabic male, diagnosed with metastatic lung adenocarcinoma, who, after several cycles of chemotherapy, presented symptoms and signs of splenic abcess. Splenic abcess is rare situation, which must be actively researched, to have access to an optimal therapeutic approach.

Molecular mechanisms of pancreatic cancer dissemination: the role of the chemokine system.

PubMed

Marchesi, Federica; Grizzi, Fabio; Laghi, Luigi; Mantovani, Alberto; Allavena, Paola

2012-01-01

Over the last decade it has been established that cancer-associated inflammation affects many aspects of malignancy and in particular endorses tumor cell survival, proliferation and distant spread. Chemokines and their receptors are major players of the cancerrelated inflammation. Our understanding of the chemokine role in tumor biology now ranges from their ability to recruit blood leukocytes within tumors, to direct effects on cancer cell survival, metastatization and regulation of angiogenesis. Chemokines and their receptors are expressed in human pancreatic adenocarcinoma and are involved in its malignant behavior. Notably, the receptor CX3CR1 favors tumor perineural tropism which is typical of this neoplasm and is associated with early recurrence after surgery and with poor patient prognosis.

Long-term benefit of PD-L1 blockade in lung cancer associated with JAK3 activation

PubMed Central

Van Allen, Eliezer M.; Golay, Hadrien G.; Liu, Yan; Koyama, Shohei; Wong, Karrie; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, Maegan; Rojas-Rudilla, Vanesa; Chevalier, Aaron; Thai, Tran; Lydon, Christine; Mach, Stacy; Wong, Joshua A.; Rabin, Alexandra R.; Helmkamp, Joshua; Sholl, Lynette; Carter, Scott L.; Oxnard, Geoffrey; Janne, Pasi; Getz, Gad; Lindeman, Neal; Hammerman, Peter S.; Garraway, Levi A.; Hodi, F. Stephen; Rodig, Scott; Dranoff, Glenn; Wong, Kwok-Kin; Barbie, David A.

2015-01-01

PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. PMID:26014096

EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus.

PubMed

Birkman, Eva-Maria; Ålgars, Annika; Lintunen, Minnamaija; Ristamäki, Raija; Sundström, Jari; Carpén, Olli

2016-07-07

Approximately 50 % of gastric adenocarcinomas belong to a molecular subgroup characterised by chromosomal instability and a strong association with the intestinal histological subtype. This subgroup typically contains alterations in the receptor tyrosine kinase-RAS pathway, for example EGFR or HER2 gene amplifications leading to protein overexpression. In clinical practice, HER2 overexpressing metastatic gastric cancer is known to respond to treatment with anti-HER2 antibodies. By contrast, anti-EGFR antibodies have not been able to provide survival benefit in clinical trials, which, however, have not included patient selection based on the histological subtype or EGFR gene copy number analysis of the tumours. To examine the role of EGFR as a potential biomarker, we studied the prevalence, clinicopathological associations as well as prognostic role of EGFR and HER2 expression and gene amplification in intestinal adenocarcinomas of the stomach, gastro-oesophageal junction and distal oesophagus. Tissue samples from 220 patients were analysed with EGFR and HER2 immunohistochemistry. Those samples with moderate/strong staining intensity were further analysed with silver in situ hybridization to quantify gene copy numbers. The results were associated with clinical patient characteristics and survival. Moderate/strong EGFR protein expression was found in 72/220 (32.7 %) and EGFR gene amplification in 31/220 (14.1 %) of the tumours, while moderate/strong HER2 protein expression was detected in 31/220 (14.1 %) and HER2 gene amplification in 29/220 (13.2 %) of the tumours. EGFR and HER2 genes were co-amplified in eight tumours (3.6 %). EGFR gene amplification was more common in tumours of distal oesophagus/gastro-oesophageal junction/cardia than in those of gastric corpus (p = 0.013). It was associated with shortened time to cancer recurrence (p = 0.026) and cancer specific survival (p = 0.033). EGFR gene amplification is relatively common in intestinal adenocarcinomas and associates with decreased survival. It is rarely concurrent with HER2 gene amplification, suggesting that anti-EGFR therapies might be applicable to some patients not eligible for anti-HER2 treatment. Analogous to HER2 testing, determination of EGFR gene amplification status in concert with immunohistochemistry could improve the specificity of patient selection when investigating the possible benefits of anti-EGFR therapies in the treatment of gastric adenocarcinomas.

Effect of different concentrations of oxygen on expression of sigma 1 receptor and superoxide dismutases in human colon adenocarcinoma cell lines.

PubMed

Skrzycki, Michał; Czeczot, Hanna; Mielczarek-Puta, Magdalena; Otto-Ślusarczyk, Dagmara; Graboń, Wojciech

2017-06-01

Tumor cells due to distance from capillary vessels exist in different oxygenation conditions (anoxia, hypoxia, normoxia). Changes in cell oxygenation lead to reactive oxygen species production and oxidative stress. Sigma 1 receptor (Sig1R) is postulated to be stress responding agent and superoxide dismutases (SOD1 and SOD2) are key antioxidant enzymes. It is possible that they participate in tumor cells adaptation to different concentrations of oxygen. Evaluation of Sig1R, SOD1, and SOD2 expression in different concentrations of oxygen (1%, 10%, 21%) in colon adenocarcinoma cell lines. SW480 (primary adenocarcinoma) and SW620 (metastatic) cell lines were cultured in standard conditions in Dulbecco's modified Eagle's medium for 5 days, and next cultured in Hypoxic Chamber in 1% O 2 , 10% O 2 , 21% O 2 . Number of living cells was determined by trypan blue assay. Level of mRNA for Sig1R, SOD1, and SOD2 was determined by standard PCR method. Statistical analysis was conducted using Statistica 10.1 software. We observed significant changes in expression of Sig1R, SOD1, SOD2 due to different oxygen concentrations. ANOVA analysis revealed significant interactions between studied parameters mainly in hypoxia conditions in SW480 cells and between Sig1R and SOD2 in SW620 cells. It also showed that changes in expression of studied proteins depend significantly on type of the cell line. Changes of Sig1R and SOD2 expression point to mitochondria as main organelle responsible for survival of tumor cells exposed to hypoxia or oxidative stress. Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen.

Correlation of metastasis characteristics with prognosis in gastric mixed adenoneuroendocrine carcinoma: Two case reports.

PubMed

Tang, Qiang; Zhou, Zili; Chen, Jinhuang; Di, Maojun; Ji, Jintong; Yuan, Wenzheng; Liu, Zhengyi; Wu, Liang; Zhang, Xudan; Li, Kang; Shu, Xiaogang

2017-12-01

This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy. The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena. The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes. The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness. The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation. The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

AB 66. One-year experience of the pulmonary department of Aristotle University of Thessaloniki in thoracoscopy with local anaesthesia (medical thoracoscopy)

PubMed Central

Spyropoulos, George; Kontakiotis, Theodoros; Spyratos, Dionysios; Iakovidis, Dimitrios; Zoglopitis, Fotis; Zarogoulidis, Konstantinos

2012-01-01

Background Thoracoscopy with local anesthesia or medical thoracoscopy is an invasive method which is rather valuable not only for the approach of undiagnosed exudative pleural effusions but also for the treatment of symptomatic malignant effusions with the conduct of pleurodesis. This is a review of those patients who underwent medical thoracoscopy in the period May 2011 to September 2012 in the Pulmonary Department the Aristotle University of Thessaloniki. Patients and methods Thirty nine thoracoscopies were conducted in our Department since May 2011. Twenty nine patients with cytological test negative for malignancy underwent diagnostic thoracoscopy. Eleven of those procedures were diagnostic and positive for malignancy, while 12 were non-diagnostic and 2 with limited evidence of malignancy. The biopsy results of 2 thoracoscopies showed granulomatous infection and other 2 nonspecific chronic inflammation. Out of all the diagnoses which were positive for malignancy, 2 were related to mesothelioma, 5 to adenocarcinoma (4 of them originated from lungs and one of unknown primary origin) while 1 patient was diagnosed with metastatic papillary adenocarcinoma originated from the thyroid and another one with lymphoma. There were also patients carrying diagnosed illness intending pleurodesis in cases of malignant recrudescent pleural effusions in mesothelioma, lung adenocarcinoma and biliary carcinoma who underwent thoracoscopy. Another patient with recrudescent pneumothorax underwent pleurodesis with talc. Results The major complications which emerged either during the procedure or after the thoracoscopy were two: one patient developed allergy in lidocaine intake for the local anesthesia having as a result to quit the procedure while another patient developed an empyema several weeks later. Conclusions Thoracoscopy with local anesthesia is a safe procedure, tolerable for the patient, which has a significant diagnostic value and only a small percentage of complications.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

PubMed

Diaz De Vivar, Andrea; Roma, Andres A; Park, Kay J; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G; Mikami, Yoshiki; Hong, Sung R; Arville, Brent; Teramoto, Norihiro; Ali-Fehmi, Rouba; Rutgers, Joanne K L; Tabassum, Farah; Barbuto, Denise; Aguilera-Barrantes, Irene; Shaye-Brown, Alexandra; Daya, Dean; Silva, Elvio G

2013-11-01

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

PubMed

Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

2012-08-09

Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

LFA-1 expression in a series of colorectal adenocarcinomas.

PubMed

Papas, Maria G; Karatzas, Pantelis S; Papanikolaou, Ioannis S; Karamitopoulou, Evanthia; Delicha, Eumorphia M; Adler, Andreas; Triantafyllou, Konstantinos; Thomopoulou, Georgia-Heleni; Patsouris, Efstratios; Lazaris, Andreas C

2012-09-01

LFA-1 is an adhesion molecule which belongs to the β2-integrin family. Overexpression of LFA-1 in hepatic natural killer cells has been associated with increased apoptosis of neoplastic cells in colorectal cancer (CRC); moreover, studies in CRC have linked LFA-1 overexpression in neoplastic cells with vascular intrusion through adhesion to endothelial cells, thus implying a possible role in creation of metastases. We studied the expression of LFA-1 in a series of 82 patients with CRC. A standard three-step immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded tissue sections. An IgG2a anti-CD11a monoclonal antibody was used. Cases were characterized according to clinicopathological variables including sex, age, tumor localization, size, grade, Dukes stage, wall invasion, and presence of metastatic lymph nodes (mLNs) or distal metastases. LFA-1 was expressed at the primary tumor site in 51 cases and 6/33 cases with metastatic lymphnodes. In Dukes D cases (n = 4), only one case was LFA-1(+). LFA-1 expression at the primary tumor site was associated with the absence of metastatic disease and with Dukes B stage. However, in those cases with LFA-1 expression in cancer cells in mLNs, this was associated with its expression at the primary tumor site. The positive association of LFA-1 expression in mLNs when the primary tumor site is also LFA-1(+) could imply an adaptation advantage of this specific cellular clone to its micro-environment, predisposing it to creation of mLNs, pointing to a role for LFA-1 in creation of mLNs in CRC.

Preferential expression of NY-BR-1 and GATA-3 in male breast cancer.

PubMed

Biserni, Giovanni Battista; Di Oto, Enrico; Moskovszky, Linda Eszter; Foschini, Maria Pia; Varga, Zsuzsanna

2018-02-01

Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer. Thirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted. 30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher's exact test. We found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.

Metastatic colonic and gastric polyps from breast cancer resembling hyperplastic polyps.

PubMed

Horimoto, Yoshiya; Hirashima, Tetsuro; Arakawa, Atsushi; Miura, Hiroyoshi; Saito, Mitsue

2018-03-23

Breast cancer metastasis to the gastrointestinal tract is relatively rare and is generally found when patients complain of symptoms such as gastrointestinal obstruction. Herein, we report a case with metastatic colonic and gastric lesions from breast cancer, with the formation of mucosal polyps which resembled typical hyperplastic polyps.A 47-year-old woman underwent curable surgery for breast cancer and received standard systemic treatments. Her primary tumor was composed of a mix of invasive lobular and ductal carcinomas. During adjuvant endocrine therapy, she developed multiple colonic metastases, identified by colonoscopy performed as part of a general health check-up. She had no symptoms. Small elevated sessile polyps in the transverse colon and rectum showed histological features of signet-ring cell type adenocarcinoma, similar to the invasive lobular component of the primary breast cancer. During treatments for recurrent disease, she also developed multiple gastric metastases, with the same endoscopic and pathological features as the colonic lesions. Her treatment regimen was switched to oral chemotherapy, and she has since maintained stable disease for nearly 3 years. Multiple bone metastases eventually developed, and she was again switched to another systemic treatment but, to date, has remained free of symptoms.We emphasize that the endoscopic findings of the metastatic lesions in the colon and stomach in this case highly resembled hyperplastic polyps. Since biopsy is not always performed for hyperplastic polyps in the gastrointestinal tract, we believe that this case report may encourage endoscopists to offer biopsies to the patient who has a history of breast cancer.

Re-engineering the Pancreas Tumor Microenvironment: A “Regenerative Program” Hacked

PubMed Central

Evan, Gerard I.; Hah, Nasun; Littlewood, Trevor D.; Sodir, Nicole M.; Vidal, Tania Campos; Downes, Michael; Evans, Ronald M.

2017-01-01

The “hallmarks” of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix and immune cells. The oncogenically-activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immune-suppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue specific repair mechanism regulated by discrete super enhancer networks. Defined as genomic regions containing clusters of multiple enhancers, super enhancers play pivotal roles in cell/tissue specification, identity and maintenance. Hence, interfering with such super enhancer driven repair networks should exert a disproportionately disruptive effect on tumor versus normal pancreatic tissue. Novel drugs that directly or indirectly inhibit processes regulating epigenetic status and integrity, including those driven by histone deacetylases, histone methyltransferase and hydroxylases, DNA methyltransferases, various metabolic enzymes, and bromodomain and extra-terminal motif proteins (BETs) have shown the feasibility of disrupting super enhancer-dependent transcription in treating multiple tumor types, including PDAC. The idea that pancreatic adenocarcinomas rely on embedded super enhancer transcriptional mechanism suggests a vulnerability that can be potentially targeted as novel therapies for this intractable disease. PMID:28373363

Stimulatory effect of desipramine on lung metastases of adenocarcinoma MADB 106 in stress highly-sensitive and stress non-reactive rats.

PubMed

Grygier, Beata; Kubera, Marta; Wrona, Danuta; Roman, Adam; Basta-Kaim, Agnieszka; Gruca, Piotr; Papp, Mariusz; Rogoz, Zofia; Leskiewicz, Monika; Budziszewska, Boguslawa; Regulska, Magdalena; Korzeniak, Barbara; Curzytek, Katarzyna; Glombik, Katarzyna; Slusarczyk, Joanna; Maes, Michael; Lason, Wladyslaw

2018-01-03

The effect of antidepressant drugs on tumor progress is very poorly recognized. The aim of the present study was to examine the effect of individual reactivity to stress and 24-day desipramine (DES) administration on the metastatic colonization of adenocarcinoma MADB 106 cells in the lungs of Wistar rats. Wistar rats were subjected to stress procedure according to the chronic mild stress (CMS) model of depression for two weeks and stress highly-sensitive (SHS) and stress non-reactive (SNR) rats were selected. SHS rats were more prone to cancer metastasis than SNR ones and chronic DES treatment further increased the number of lung metastases by 59% and 50% in comparison to vehicle-treated appropriate control rats. The increase in lung metastases was connected with DES-induced skew macrophage activity towards M2 functional phenotype in SHS and SNR rats. Moreover, during 24h after DES injection in healthy rats, the decreased number of TCD8 + and B cells in SHS and SNR rats as well as NK cell cytotoxic activity in SNR rats could be attributed to the lowered capacity to defend against cancer metastasis observed in chronic DES treated and tumor injected rats. Copyright © 2017. Published by Elsevier Inc.

Stem cells as the root of pancreatic ductal adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes

2012-04-01

Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulationsmore » that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.« less

Advances in the treatment of gastric cancer.

PubMed

Ilson, David H

2017-11-01

To review recent studies in esophagogastric cancer. Positive emission tomography (PET) scan in follow-up after curative treatment of esophagogastric cancer did not lead to improved survival. In the preoperative treatment of esophagogastric cancer, the addition of the antivascular endothelial growth factor agent bevacizumab to perioperative chemotherapy with combination epirubicin, cisplatinum, and 5-fluorouracil (5-FU; ECF) failed to improve survival compared with chemotherapy alone. In a head-to-head comparison of preoperative chemotherapy for locally advanced gastric and esophagogastric adenocarcinoma, FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved overall survival compared with ECF. Assessing response to induction chemotherapy prior to combined preoperative chemoradiotherapy in PET nonresponding patients allowed a change in chemotherapy during subsequent radiotherapy with improved rates of pathologic complete response. In human epidermal growth factor receptor-2-positive advanced esophagogastric adenocarcinoma, second-line treatment with the chemotherapy/trastuzumab drug conjugate emtansine/trastuzumab failed to improve response or overall survival compared with treatment using paclitaxel chemotherapy. The immune checkpoint inhibitor, nivolumab, improved survival in refractory gastric cancer. Recent studies in gastric cancer clarify the optimal preoperative chemotherapy regimen and the use of PET scan as a response measure of preoperative therapy in esophagogastric cancer, and the role of targeted agents and immune checkpoint inhibitors in metastatic disease.

Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion

PubMed Central

Yazdani, Hamza O.; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L.; Tsung, Allan

2017-01-01

Introduction Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Methods Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. Results After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines. Conclusions DRPs significantly attenuated metastatic tumor development and growth. DRPs warrant further investigation as a potential treatment for liver I/R injury in the clinical setting to improve cancer-specific outcomes. PMID:28938688

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years

PubMed Central

Hall, Bradley R.; Cannon, Andrew; Atri, Pranita; Wichman, Christopher S.; Smith, Lynette M.; Ganti, Apar K.; Are, Chandrakanth; Sasson, Aaron R.; Kumar, Sushil; Batra, Surinder K.

2018-01-01

Background In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. Materials and methods All Phase 2–4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. Results Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). Conclusions Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. Funding The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586). PMID:29721211

Branched Chain RNA In Situ Hybridization for Androgen Receptor Splice Variant AR-V7 as a Prognostic Biomarker for Metastatic Castration-Sensitive Prostate Cancer.

PubMed

Saylor, Philip J; Lee, Richard J; Arora, Kshitij S; Deshpande, Vikram; Hu, Rong; Olivier, Kara; Meneely, Erika; Rivera, Miguel N; Ting, David T; Wu, Chin-Lee; Miyamoto, David T

2017-01-15

The androgen receptor (AR) mRNA splice variant AR-V7 has emerged as a predictive biomarker for response to AR-targeted therapies. There are currently no commercially available assays to detect AR splice variants. The branched chain RNA in situ hybridization (ISH) platform enables the highly sensitive detection of RNA transcripts in formalin-fixed, paraffin-embedded (FFPE) tissues. We designed a branched chain RNA ISH probe to target the unique cryptic exon CE3 of AR-V7 using multiple tiling probes. This automated ISH assay was applied to tumor tissue from two distinct clinical cohorts that we hypothesized would differ in AR-V7 status. We detected AR-V7 in all tumor samples from men with metastatic castration-resistant prostate cancer with tissue obtained after disease progression despite at least one subsequent line of hormonal therapy (abiraterone, enzalutamide, or bicalutamide; n = 12). We detected AR-V7 in just one tumor from men who had undergone prostatectomy for localized adenocarcinoma (n = 30; Gleason 4 + 5 = 9 in the AR-V7-positive sample). Given the apparent distinction between the above groups by AR-V7 signal, we analyzed pretreatment AR-V7 status as a predictive and prognostic biomarker in men with treatment-naïve metastatic disease. Patients with metastases but without detectable AR-V7 RNA at baseline had significantly longer overall survival (log-rank P = 0.044) and a trend toward superior progression-free survival (log-rank P = 0.055). Within an institutional cohort, the RNA ISH assay identified AR-V7 within FFPE tissue and may have prognostic value in metastatic castration-sensitive prostate cancer. These preliminary findings warrant further study in larger cohorts. Clin Cancer Res; 23(2); 363-9. ©2016 AACR. ©2016 American Association for Cancer Research.

The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity.

PubMed

Liu, Wendy; Fackler, William; Rice, Thomas W; Richter, Joel E; Achkar, Edgar; Goldblum, John R

2002-06-01

Pseudoachalasia is an esophageal motor disorder usually associated with malignancy that has clinical, radiographic, and manometric findings that are often indistinguishable from primary achalasia. There are few reports examining the histologic features of the associated neoplasms and their relationship with the esophageal myenteric plexus. We studied the clinical and pathologic features of 13 cases of pseudoachalasia seen at our institution between 1979 and 1999. Detailed clinical and radiographic data were obtained from medical records. In all cases available histologic material was reviewed to confirm the presence and type of associated neoplasm. When possible, the relationship of the neoplasm to the esophageal myenteric plexus was examined. In selected cases immunohistochemical stains were performed to further evaluate this relationship. All patients had clinical, radiographic, and manometric features similar to primary achalasia. The cohort included seven men and six women, age range 24-79 years (median 61 years). Associated neoplasms included esophageal adenocarcinoma arising in Barrett's esophagus (n = 1), adenocarcinoma of the esophagogastric junction (n = 7), metastatic renal cell carcinoma to the esophagogastric junction (n = 1), breast adenocarcinoma (n = 1), pulmonary small cell carcinoma (n = 1), pleural malignant mesothelioma (n = 1), and mediastinal fibrosis (n = 1). The mechanism of pseudoachalasia was consistent with neoplastic infiltration of the esophageal myenteric plexus in 11 cases. Neoplastic cells surrounded myenteric ganglion cells, which appeared normal in number and morphology. In the patient with pulmonary small cell carcinoma, there was no evidence of neoplastic infiltration of the esophagogastric junction, and anti-ANNA-1 antibody was detected, suggesting a paraneoplastic syndrome. Tissue obtained at the time of esophagomyotomy revealed lymphocytic myenteric inflammation and marked depletion of ganglion cells identical to that seen in primary achalasia. The mechanism pseudoachalasia in the patient with breast adenocarcinoma is uncertain, as there was no evidence of direct involvement of the esophagogastric junction. In summary, we describe 13 cases of pseudoachalasia resulting in a clinical syndrome indistinguishable from primary achalasia. The most common mechanism is direct involvement of the esophageal myenteric plexus by neoplastic cells. Rarely, a distant neoplasm may cause this syndrome as a paraneoplastic process.

[Current standards in the treatment of gastric cancer].

PubMed

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

Biodistribution detection of Photofrin porfimer sodium and benzoporphyrin derivative using a fiber optic sensor and ratio fluorometry

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; Papazoglou, Theodore G.; Papaioannou, Thanassis; Stavridi, Marigo; Pergadia, Vani R.; Fishbein, Michael C.; van der Veen, Maurits J.; Thomas, Reem; Grundfest, Warren S.

1994-03-01

Laser induced fluorescence spectroscopy (LIFS) was used to detect the presence of PHOTOFRINR porfimer sodium and Benzoporphyrin derivative-monoacid, ring A (BPD-MA) in various tissues. Lobund Wistar rats (n equals 49) inoculated with rat prostatic adenocarcinoma (PA-III) were injected with PHOTOFRINR porfimer sodium (7.5 - 0.25 mg/kg) and BPD (0.50 - 25 mg/kg) intravenously. A Helium-Cadmium laser (442 nm) was used as an excitation source. Our study showed that the amount of PHOTOFRINR porfimer sodium and BPD-MA which localizes in the metastatic lymph nodes is higher than in tumor and all other healthy tissues. Laser induced fluorescence spectroscopy may be a feasible method to detect the distribution of photosensitizers or other fluorescent compounds in vivo.

Metastatic lung adenocarcinoma related α-Fetoprotein elevation in a patient with HBV-related cirrhosis.

PubMed

Hamamci, Mevlut; Karaahmet, Fatih; Akinci, Hakan; Kilincalp, Serta; Acıkgoz, Ruchan; Coban, Sahin; Yuksel, Ilhami

2015-12-01

HCC is the most common type of primary liver tumor. The Practice Guideline, AASLD, for HCC recommended surveillance of HBV carriers at high risk of HCC with US every 6-12 months. Laboratory surveillance option is the measurement of serum α-fetoprotein level which has long been used for the diagnosis of HCC. But, increased serum levels of α-fetoprotein are also seen in acute hepatitis, cirrhosis, and malignancies include yolk sac carcinoma, neuroblastoma, hepatoblastoma, gastric and lung carcinoma. Because of elevation α-fetoprotein in these malignancies, liver mass with an elevated α-fetoprotein does not directly indicate HCC. For these reason, clinicians evaluating patient with liver mass and HBV-related cirrhosis should be vigilant for other case of α-fetoprotein elevation. © Acta Gastro-Enterologica Belgica.

Management of penoscrotal extramammary Paget disease: case series and review of the literature

PubMed Central

Moretto, P.; Nair, V.J.; Hallani, S. El; Malone, S.; Belanger, E.; Morash, C.; Canil, C.M.

2013-01-01

Extramammary Paget disease (empd) is a rare, slow-growing neoplasm, considered to be an adenocarcinoma of the apocrine glands. In men, the penoscrotal region is the most commonly affected area. The disease can present as carcinoma in situ or as invasive disease that can subsequently metastasize to lymph nodes and distant sites. Because of the rarity of empd, the medical literature available to guide management of the disease is limited, particularly in patients with metastases. In addition, metastatic disease may pose a diagnostic challenge, because invasive cancer of the genitourinary or gastrointestinal tract can occur in association with empd. In the present case series, we describe our experience in treating penoscrotal empd with multimodality therapy, and we review the existing literature concerning its diagnosis and management. PMID:23904770

Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer.

PubMed

Ito, Daisuke; Yogosawa, Satomi; Mimoto, Rei; Hirooka, Shinichi; Horiuchi, Takashi; Eto, Ken; Yanaga, Katsuhiko; Yoshida, Kiyotsugu

2017-08-01

Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran.

PubMed

Koochak, Aghigh; Rakhshani, Nasser; Karbalaie Niya, Mohammad Hadi; Tameshkel, Fahimeh Safarnezhad; Sohrabi, Masoud Reza; Babaee, Mohammad Reza; Rezvani, Hamid; Bahar, Babak; Imanzade, Farid; Zamani, Farhad; Khonsari, Mohammad Reza; Ajdarkosh, Hossein; Hemmasi, Gholamreza

2016-01-01

The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

Factors Associated with Life Expectancy in Patients with Metastatic Spine Disease from Adenocarcinoma of the Lung

PubMed Central

Goodwin, C. Rory; Khattab, Mohamed H.; Sankey, Eric W.; Elder, Benjamin D.; Kosztowski, Thomas A.; Sarabia-Estrada, Rachel; Bydon, Ali; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L.; Sciubba, Daniel M.

2015-01-01

Study Design Retrospective study. Objective Our objective was to identify preoperative prognostic factors associated with survival in patients with spinal metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients diagnosed with lung carcinoma metastatic to the spinal column was performed to determine factors associated with survival. We used 3 months survival as the clinical cutoff for whether surgical intervention should be performed. We analyzed patients who survived less than 3 months compared with those who survived more than 3 months. Demographic, preoperative, operative, and postoperative factors including functional scores were collected for analysis. Results The median survival for all patients in our study was 3.5 months. We found a statistically significant difference between the group that survived less than 3 months and the group that survived greater than 3 months in terms of extrathoracic metastasis, visceral metastasis, and average postoperative modified Rankin score. Conclusion Determining which patients with lung cancer spinal metastases will benefit from surgical intervention is often dictated by the patient's predicted life expectancy. Factors associated with poorer prognosis include age, functional status, visceral metastases, and extrathoracic metastases. Although the prognosis for patients with lung cancer spinal metastases is poor, some patients may experience long-term benefit from surgical intervention. PMID:26430597

MR Fingerprinting for Rapid Quantitative Abdominal Imaging

PubMed Central

Chen, Yong; Jiang, Yun; Pahwa, Shivani; Ma, Dan; Lu, Lan; Twieg, Michael D.; Wright, Katherine L.; Seiberlich, Nicole; Griswold, Mark A.

2016-01-01

Purpose To develop a magnetic resonance (MR) “fingerprinting” technique for quantitative abdominal imaging. Materials and Methods This HIPAA-compliant study had institutional review board approval, and informed consent was obtained from all subjects. To achieve accurate quantification in the presence of marked B0 and B1 field inhomogeneities, the MR fingerprinting framework was extended by using a two-dimensional fast imaging with steady-state free precession, or FISP, acquisition and a Bloch-Siegert B1 mapping method. The accuracy of the proposed technique was validated by using agarose phantoms. Quantitative measurements were performed in eight asymptomatic subjects and in six patients with 20 focal liver lesions. A two-tailed Student t test was used to compare the T1 and T2 results in metastatic adenocarcinoma with those in surrounding liver parenchyma and healthy subjects. Results Phantom experiments showed good agreement with standard methods in T1 and T2 after B1 correction. In vivo studies demonstrated that quantitative T1, T2, and B1 maps can be acquired within a breath hold of approximately 19 seconds. T1 and T2 measurements were compatible with those in the literature. Representative values included the following: liver, 745 msec ± 65 (standard deviation) and 31 msec ± 6; renal medulla, 1702 msec ± 205 and 60 msec ± 21; renal cortex, 1314 msec ± 77 and 47 msec ± 10; spleen, 1232 msec ± 92 and 60 msec ± 19; skeletal muscle, 1100 msec ± 59 and 44 msec ± 9; and fat, 253 msec ± 42 and 77 msec ± 16, respectively. T1 and T2 in metastatic adenocarcinoma were 1673 msec ± 331 and 43 msec ± 13, respectively, significantly different from surrounding liver parenchyma relaxation times of 840 msec ± 113 and 28 msec ± 3 (P < .0001 and P < .01) and those in hepatic parenchyma in healthy volunteers (745 msec ± 65 and 31 msec ± 6, P < .0001 and P = .021, respectively). Conclusion A rapid technique for quantitative abdominal imaging was developed that allows simultaneous quantification of multiple tissue properties within one 19-second breath hold, with measurements comparable to those in published literature. © RSNA, 2016 PMID:26794935

Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.

PubMed

Zhang, Jing-Jing; Zhu, Yi; Xie, Kun-Ling; Peng, Yun-Peng; Tao, Jin-Qiu; Tang, Jie; Li, Zheng; Xu, Ze-Kuan; Dai, Cun-Cai; Qian, Zhu-Yin; Jiang, Kui-Rong; Wu, Jun-Li; Gao, Wen-Tao; Du, Qing; Miao, Yi

2014-05-29

Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software. We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.

MR Fingerprinting for Rapid Quantitative Abdominal Imaging.

PubMed

Chen, Yong; Jiang, Yun; Pahwa, Shivani; Ma, Dan; Lu, Lan; Twieg, Michael D; Wright, Katherine L; Seiberlich, Nicole; Griswold, Mark A; Gulani, Vikas

2016-04-01

To develop a magnetic resonance (MR) "fingerprinting" technique for quantitative abdominal imaging. This HIPAA-compliant study had institutional review board approval, and informed consent was obtained from all subjects. To achieve accurate quantification in the presence of marked B0 and B1 field inhomogeneities, the MR fingerprinting framework was extended by using a two-dimensional fast imaging with steady-state free precession, or FISP, acquisition and a Bloch-Siegert B1 mapping method. The accuracy of the proposed technique was validated by using agarose phantoms. Quantitative measurements were performed in eight asymptomatic subjects and in six patients with 20 focal liver lesions. A two-tailed Student t test was used to compare the T1 and T2 results in metastatic adenocarcinoma with those in surrounding liver parenchyma and healthy subjects. Phantom experiments showed good agreement with standard methods in T1 and T2 after B1 correction. In vivo studies demonstrated that quantitative T1, T2, and B1 maps can be acquired within a breath hold of approximately 19 seconds. T1 and T2 measurements were compatible with those in the literature. Representative values included the following: liver, 745 msec ± 65 (standard deviation) and 31 msec ± 6; renal medulla, 1702 msec ± 205 and 60 msec ± 21; renal cortex, 1314 msec ± 77 and 47 msec ± 10; spleen, 1232 msec ± 92 and 60 msec ± 19; skeletal muscle, 1100 msec ± 59 and 44 msec ± 9; and fat, 253 msec ± 42 and 77 msec ± 16, respectively. T1 and T2 in metastatic adenocarcinoma were 1673 msec ± 331 and 43 msec ± 13, respectively, significantly different from surrounding liver parenchyma relaxation times of 840 msec ± 113 and 28 msec ± 3 (P < .0001 and P < .01) and those in hepatic parenchyma in healthy volunteers (745 msec ± 65 and 31 msec ± 6, P < .0001 and P = .021, respectively). A rapid technique for quantitative abdominal imaging was developed that allows simultaneous quantification of multiple tissue properties within one 19-second breath hold, with measurements comparable to those in published literature.

Occult Metastases in Pelvic Lymphadenectomy Specimens From Patients With Urothelial Carcinoma of the Bladder.

PubMed

Gordetsky, Jennifer; Gibson, Briana; Stevens, Todd M; Ellenburg, J Luke; Grizzle, William; Rais-Bahrami, Soroush

2016-08-01

To identify occult metastases within lymph nodes (LNs) reported as negative by routine histologic evaluation. In patients with high-grade, muscle-invasive urothelial carcinoma (UC) of the bladder, pelvic lymphadenectomy during radical cystectomy demonstrates a survival advantage, increasing with the number of LNs removed, even if negative for metastatic disease. This finding may potentially be explained by the presence of occult metastases. Radical cystectomy specimens with high-grade UC invading the perivesical tissue and negative LNs (pT3N0) between 2000 and 2014 were reviewed. Five levels were cut for each LN block. Two sections were cut per level: 1 stained for hematoxylin and eosin and 1 for AE1/AE3. Micrometastases were defined as tumor deposits >0.2 mm but <2 mm. Isolated tumor cells were defined as ≤0.2 mm. Medical records and survival data were reviewed. We identified 21 cases, consisting of 370 lymph nodes. Six of 21 patients (29%) had occult metastases, including 5 occult metastatic UC and 1 occult metastatic prostate adenocarcinoma. There were 10 positive LNs; 2 macrometastases, 2 micrometastases, and 6 with ITCs. Two of 6 patients (33%) had lymphovascular invasion identified in the primary tumor. Kaplan-Meier analysis showed no significant difference in overall survival between the group of patients who remained N0 versus those upstaged due to discovery of occult metastases (P-value = .42). In patients with pT3 UC undergoing cystectomy, we demonstrated the presence of occult metastases in 29% of patients. The high percentage of occult metastases present in these cases possibly explains the proven survival advantage of removing "negative" LNs. This finding might also have implications in the histologic evaluation of LNs. Copyright © 2016 Elsevier Inc. All rights reserved.

The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.

PubMed

Gurzu, Simona; Banias, Laura; Bara, Tivadar; Feher, I; Bara, Tivadar; Jung, Ioan

2018-01-01

Metastases to the stomach are extremely rare and the metastatic pathway is not well understood. To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells. The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents. In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, β-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma. In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/β-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Minimally invasive "separation surgery" plus adjuvant stereotactic radiotherapy in the management of spinal epidural metastases.

PubMed

Turel, Mazda K; Kerolus, Mena G; O'Toole, John E

2017-01-01

This study aimed to describe the application of minimally invasive surgery (MIS) in separation surgery combined with postoperative stereotactic body radiation therapy (SBRT) in patients with symptomatic metastatic epidural spinal disease. Three techniques are described: (1) MIS posterior separation surgery alone, (2) MIS posterolateral separation surgery with percutaneous pedicle screw placement, and (3) MIS lateral corpectomy with percutaneous pedicle screw placement. Seven representative cases are presented in which the above techniques were applied and after which postoperative SBRT was performed. The seven representative patients (3 male, 4 female) had a mean age of 54 years (range, 46-62 years). Two patients had a primary diagnosis of cholangiocarcinoma and in one patient each a diagnosis of breast, renal, lung adenocarcinoma, melanoma, and urothelial squamous cell carcinoma as their primary tumor. All patients had additional multiorgan disease apart from the metastatic spine involvement. Three patients underwent operations in the lumbar spine, two in the thoracic spine, and one in each of the thoraco-lumbar and lumbo-sacral spine. The average operating time was 149 ± 60.3 min (range, 90-240 min). The mean estimated blood loss was 188.8 cc. The mean length of stay in the hospital was 4 days (range, 3-7 days). There were no surgical complications. All patients received postoperative SBRT (typically 24 Gy in 3 fractions) at a mean of 43.2 days after surgery (range, 30-83). Early reports such as this suggest that MIS techniques can be successfully and safely applied in accomplishing "separation surgery" with adjuvant SBRT in the management of metastatic spinal disease. The potential advantages conferred by MIS techniques such as shortened hospital stay, decreased blood loss, reduced perioperative complications, and earlier initiation of adjuvant radiation are highly desirable in the treatment of this challenging patient population.

Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis.

PubMed

Kudinov, Alexander E; Deneka, Alexander; Nikonova, Anna S; Beck, Tim N; Ahn, Young-Ho; Liu, Xin; Martinez, Cathleen F; Schultz, Fred A; Reynolds, Samuel; Yang, Dong-Hua; Cai, Kathy Q; Yaghmour, Khaled M; Baker, Karmel A; Egleston, Brian L; Nicolas, Emmanuelle; Chikwem, Adaeze; Andrianov, Gregory; Singh, Shelly; Borghaei, Hossein; Serebriiskii, Ilya G; Gibbons, Don L; Kurie, Jonathan M; Golemis, Erica A; Boumber, Yanis

2016-06-21

Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of Kras(LA1/+);P53(R172HΔG/+) (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial-mesenchymal transition, including the TGF-β receptor 1 (TGFβR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFβRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2-dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial-mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFβR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness.

Safety and pharmacokinetics of ramucirumab in combination with docetaxel in Japanese patients with locally advanced or metastatic breast cancer: a Phase Ib study.

PubMed

Masuda, Norikazu; Iwata, Hiroji; Aogi, Kenjiro; Xu, Yihuan; Ibrahim, Ayman; Gao, Ling; Dalal, Rita; Yoshikawa, Reigetsu; Sasaki, Yasutsuna

2016-12-01

The primary objective of this study was to investigate the safety and tolerability and to confirm the recommended dose of the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab in combination with docetaxel in Japanese patients with metastatic/locally advanced breast cancer. In this multicenter, single-arm, Phase Ib trial, eligibility criteria included: 20 years or older, Eastern Cooperative Oncology Group performance status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2-negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients received docetaxel (75 mg/m 2 ) followed by ramucirumab (10 mg/kg) on Day 1 of 21-day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose-limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics, immunogenicity and antitumor activity were examined. Seven patients were treated. Most adverse events were mild to moderate. Two patients during Cycle 1 experienced a dose-limiting toxicity; one patient each experienced Grade 3 febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities subsequently resolved. No patients discontinued study therapies during Cycle 1. Four serious adverse events were possibly related to ramucirumab in combination with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic analysis revealed low total body clearance and long apparent terminal elimination half-life (~7-12 days). Partial response was reported in four patients. The combination of ramucirumab and docetaxel was tolerable in female Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with docetaxel (75 mg/m 2 ) was confirmed as the recommended dose among Japanese patients, supporting its use in future studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

PubMed

Prpić, Marin; Fröbe, Ana; Zadravec, Dijana; Pažanin, Leo; Jakšić, Blanka; Bolanča, Ante; Kusić, Zvonko

2015-06-01

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer.

PubMed

Nicoś, Marcin; Krawczyk, Paweł; Jarosz, Bożena; Sawicki, Marek; Szumiłło, Justyna; Trojanowski, Tomasz; Milanowski, Janusz

2016-05-01

KRAS mutations are associated with tumor resistance to EGFR TKIs (erlotinib, gefitinib) and to monoclonal antibody against EGFR (cetuximab). Targeted treatment of mutated RAS patients is still considered as a challenge. Inhibitors of c-Met (onartuzumab or tiwantinib) and MEK (selumetinib-a dual inhibitor of MEK1 and MEK2) signaling pathways showed activity in patients with mutations in KRAS that can became an effective approach in carriers of such disorders. BRAF mutation is very rare in patients with NSCLC, and its presence is associated with sensitivity of tumor cells to BRAF inhibitors (vemurafenib, dabrafenib). In the present study, the frequency and type of KRAS and BRAF mutation were assessed in 145 FFPE tissue samples from CNS metastases of NSCLC. In 30 patients, material from the primary tumor was simultaneously available. Real-time PCR technique with allele-specific molecular probe (KRAS/BRAF Mutation Analysis Kit, Entrogen, USA) was used for molecular tests. KRAS mutations were detected in 21.4 % of CNS metastatic lesions and in 23.3 % of corresponding primary tumors. Five mutations were identified both in primary and in metastatic lesions, while one mutation only in primary tumor and one mutation only in the metastatic tumor. Most of mutations were observed in codon 12 of KRAS; however, an individual patient had diagnosed a rare G13D and Q61R substitutions. KRAS mutations were significantly more frequent in adenocarcinoma patients and smokers. Additional analysis indicated one patient with rare coexistence of KRAS and DDR2 mutations. BRAF mutation was not detected in the examined materials. KRAS frequency appears to be similar in primary and CNS.

A phase II study of sorafenib in recurrent and/or metastatic salivary gland carcinomas: Translational analyses and clinical impact.

PubMed

Locati, L D; Perrone, F; Cortelazzi, B; Bergamini, C; Bossi, P; Civelli, E; Morosi, C; Lo Vullo, S; Imbimbo, M; Quattrone, P; Dagrada, G P; Granata, R; Resteghini, C; Mirabile, A; Alfieri, S; Orlandi, E; Mariani, L; Saibene, G; Pilotti, S; Licitra, L

2016-12-01

Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT). Patients received sorafenib at 400 mg BID. The primary end-point was response rate (RR) including complete response or partial response (PR); secondary end-points included RR according to Choi criteria, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Thirty-seven patients (19 adenoid cystic cancers, ACC) were enrolled. Six PRs were recorded. RR was 16% (95% confidence interval [CI]: 6-32; 11% in ACC and 22% in non-ACC). Choi criteria could be applied in 30 out of 37 cases with a RR of 50% (95% CI: 31-69%); DCR was 76% (95% CI: 59-88%). Incidence of ≥G3 adverse events was 29.7%. Median PFS and OS for the entire population were 5.9 months and 23.4 months, respectively. Median PFS and OS were 8.9 and 26.4 months for ACC versus 4.2 and 12.3 months for non-ACC patients. All the cases showed expression of PDGFRβ in the stroma and VEGFR2 in endothelial cells; PDGFRα positivity was found in the stroma of four (27%) cases. All except for two cases showed no PDGFRβ, VEGFR2 and PDGFRα expression in the tumour cells. KIT expression was restricted to ACC and a weak RET expression was limited to one adenocarcinoma, not otherwise specified (NOS). No BRAF mutation was found. No correlation was observed between the sorafenib activity and the expression of its markers although all six responders (two ACC, one adenocarcinoma, NOS, one salivary duct cancer [SDC], one high-grade mucoepidermoid [HG-MEC] and one poorly-differentiated cancer) are enriched in the stromal component showing a PDGFRβ immunodecoration. In ACCs, immunohistochemistry revealed MYB protein expression in 15/16 cases (94%) and the MYB-NFIB fusion oncogene was observed in 9/14 (64%). Sorafenib is the first anti-angiogenic agent to demonstrate activity in RMSGC patients, particularly in some histotypes such as HG-MEC, SDC and adenocarcinoma, NOS. The PDGFRβ-positive rich stromal component characterising these histotypes and the lack of correlation between the activity of sorafenib and its targets suggests anti-angiogenic effect as the prevalent mechanism of action of sorafenib in SGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Can extracapsular lymph node involvement be a tool to fine-tune pN1 for adenocarcinoma of the oesophagus and gastro-oesophageal junction in the Union Internationale contre le Cancer (UICC) TNM 7th edition?†.

PubMed

Nafteux, Philippe; Lerut, Toni; De Hertogh, Gert; Moons, Johnny; Coosemans, Willy; Decker, Georges; Van Veer, Hans; De Leyn, Paul

2014-06-01

The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LN's-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

PubMed Central

Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

2008-01-01

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133– subset, which is also capable of tumor initiation in NOD/SCID mice. PMID:18497886

Re-engineering the Pancreas Tumor Microenvironment: A "Regenerative Program" Hacked.

PubMed

Evan, Gerard I; Hah, Nasun; Littlewood, Trevor D; Sodir, Nicole M; Campos, Tania; Downes, Michael; Evans, Ronald M

2017-04-01

The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks. Defined as genomic regions containing clusters of multiple enhancers, super enhancers play pivotal roles in cell/tissue specification, identity, and maintenance. Hence, interfering with such super enhancer-driven repair networks should exert a disproportionately disruptive effect on tumor versus normal pancreatic tissue. Novel drugs that directly or indirectly inhibit processes regulating epigenetic status and integrity, including those driven by histone deacetylases, histone methyltransferase and hydroxylases, DNA methyltransferases, various metabolic enzymes, and bromodomain and extraterminal motif proteins, have shown the feasibility of disrupting super enhancer-dependent transcription in treating multiple tumor types, including PDAC. The idea that pancreatic adenocarcinomas rely on embedded super enhancer transcriptional mechanisms suggests a vulnerability that can be potentially targeted as novel therapies for this intractable disease. Clin Cancer Res; 23(7); 1647-55. ©2017 AACR See all articles in this CCR Focus section, "Pancreatic Cancer: Challenge and Inspiration." ©2017 American Association for Cancer Research.

Lung cancer in patients younger than 40 years in a multiracial Asian country.

PubMed

Liam, C K; Lim, K H; Wong, C M

2000-12-01

This study aimed to determine whether the clinicopathological features of lung cancer in patients younger than 40 years differ from that of older patients in an Asian country. We undertook a review of the clinicopathological data of all patients with confirmed primary lung cancer at the Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, from October 1991 to September 1999. Of the 580 patients with lung cancer, 36 (6.2%; 23 males, 13 females) were 21-39 years old at diagnosis. The percentage of people who had never smoked was higher among the younger patients (58.3% vs 19.1%, P < 0.001). Although adenocarcinoma was the most common cell type in both groups, its incidence was higher in the younger patients (24/36 (66.7%) vs 228/544 (41.9%), P = 0.007). The mean World Health Organization performance status at presentation was worse in the younger patients (2.4 vs 2, P = 0.007). In the case of non-small cell lung cancer, all the younger patients presented with either stage IIIb or metastatic disease compared to 77.2% of the older patients (P < 0.001). Younger lung cancer patients were more likely than older patients to have never smoked, to have adenocarcinoma, and to present with poorer performance status and with more advanced-stage non-small cell lung cancer.