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Sample records for rectal gastrointestinal stromal

  1. Skull metastasis from rectal gastrointestinal stromal tumours.

    PubMed

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach.

  2. Giant rectal gastrointestinal stromal tumours: a diagnostic and therapeutic challenge

    PubMed Central

    Alder, L.S.; Elver, G.; Foo, F.J.; Dobson, M.

    2013-01-01

    Gastrointestinal stromal tumour (GIST are the most common mesenchymal tumours; however, rectal GISTs account for <5%. In the pelvis they represent a diagnostic challenge with giant GISTs likely to be malignant. They may present with urological, gynaecological or rectal symptoms. Sphincter-preserving surgery can be aided by neoadjuvant therapy. We present an uncommon case of giant rectal GIST masquerading as acute urinary retention. PMID:24968434

  3. What's New in Gastrointestinal Stromal Tumor Research and Treatment?

    MedlinePlus

    ... Stromal Tumor (GIST) About Gastrointestinal Stromal Tumor What’s New in Gastrointestinal Stromal Tumor Research and Treatment? There ... the Key Statistics About Gastrointestinal Stromal Tumors? What’s New in Gastrointestinal Stromal Tumor Research and Treatment? More ...

  4. What Are the Risk Factors for Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... Gastrointestinal Stromal Tumors Be Prevented? Gastrointestinal Stromal Tumor (GIST) Causes, Risk Factors, and Prevention What Are the ... few known risk factors for gastrointestinal stromal tumors (GISTs). Being older These tumors can occur in people ...

  5. What Are the Key Statistics about Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... About Gastrointestinal Stromal Tumor What Are the Key Statistics About Gastrointestinal Stromal Tumors? Gastrointestinal stromal tumors (GISTs) ... They are slightly more common in men. Survival statistics for GIST are discussed in “ Survival rates for ...

  6. Ghrelin and gastrointestinal stromal tumors

    PubMed Central

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-01-01

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs. PMID:28348480

  7. Ghrelin and gastrointestinal stromal tumors.

    PubMed

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-03-14

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  8. What Happens After Treatment for Gastrointestinal Stromal Tumor?

    MedlinePlus

    ... Tumor Is No Longer Working Gastrointestinal Stromal Tumor (GIST) After Treatment What Happens After Treatment for Gastrointestinal ... For some people with a gastrointestinal stromal tumor (GIST), treatment may remove or destroy the cancer. Completing ...

  9. Gastrointestinal Stromal Tumours: An Update

    PubMed Central

    Somerhausen, Nicolas De Saint Aubain

    1998-01-01

    Purpose. To study the evolution of concepts concerning gastrointestinal stromal tumours (GISTs) over 30 years. Discussion. GISTs have been, for more than 30 years, the subject of considerable controversy regarding their line of differentiation as well as the prediction of their behaviour. Furthermore, once they spread within the peritoneal cavity, they are extremely hard to control. The recent findings of c-Kit mutations and the immunohistochemical detection of the product of this gene, KIT or CD117, in the mainly non-myogenic subset of this family of tumours, has led to a reappraisal of this group of lesions, which, with some exceptions, is now thought to be derived from the interstitial cells of Cajal, and this has facilitated a clearer definition of their pathological spectrum. In this article, we review chronologically the evolution of the concept of GIST with the gradual application of electron microscopy, immunohistochemistry, DNA ploidy analysis. We discuss the impact of these techniques on the pathological assessment and clinical management of GISTs. PMID:18521245

  10. Tumeur stromale rectale: à propos d'une observation

    PubMed Central

    Rejab, Haitham; Kridis, Wala Ben; Ben Ameur, Hazem; Feki, Jihene; Frikha, Mounir; Beyrouti, Mohamed Issam

    2014-01-01

    Les tumeurs stromales gastro-intestinales sont des tumeurs mésenchymateuses peu fréquentes. Elles sont localisées préférentiellement eu niveau de l'estomac. La localisation rectale reste rare. A un nouveau cas de tumeur stromale du rectum ainsi qu'une bref revue de la littérature, on se propose d’étudier les particularités cliniques, radiologiques et thérapeutiques de cette entité rare. PMID:25120863

  11. Gastrointestinal stromal tumors: the histology report.

    PubMed

    Dei Tos, Angelo P; Laurino, Licia; Bearzi, Italo; Messerini, Luca; Farinati, Fabio

    2011-03-01

    Gastrointestinal stromal tumors (GISTs) represent a mesenchymal neoplasm occurring primarily in the gastrointestinal tract, and showing differentiation toward the interstitial cell of Cajal. Its incidence is approximately 15 case/100,000/year. Stomach and small bowel are the most frequently affected anatomic sites. GIST represents a morphological, immunophenotypical and molecular distinct entity, the recognition of which has profound therapeutic implications. In fact, they have shown an exquisite sensitivity to treatment with the tyrosine kinase inhibitor imatinib. Diagnosis relies upon morphology along with immunodetection of KIT and/or DOG1. When dealing with KIT negative cases, molecular analysis of KIT/PDGFRA genes may help in confirming diagnosis. Molecular evaluation of both genes are in any case recommended as mutational status provides key predictive information. Pathologists also play a key role in providing an estimation of the risk of biological aggressiveness, which is currently based on anatomic location of the tumor, size, and mitotic activity.

  12. Laparoscopic resection of duodenal gastrointestinal stromal tumour

    PubMed Central

    Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris

    2017-01-01

    Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485

  13. Imatinib treatment for gastrointestinal stromal tumour (GIST).

    PubMed

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.

  14. Imatinib treatment for gastrointestinal stromal tumour (GIST)

    PubMed Central

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734

  15. Update on Gastrointestinal Stromal Tumors for Radiologists

    PubMed Central

    Baheti, Akshay D.; Tirumani, Harika; O'Neill, Ailbhe; Jagannathan, Jyothi P.

    2017-01-01

    The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences. PMID:28096720

  16. Targeted therapy of gastrointestinal stromal tumours

    PubMed Central

    Jakhetiya, Ashish; Garg, Pankaj Kumar; Prakash, Gaurav; Sharma, Jyoti; Pandey, Rambha; Pandey, Durgatosh

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs. PMID:27231512

  17. Gastrointestinal stromal tumors (GISTs) and second malignancies

    PubMed Central

    Rodriquenz, Maria Grazia; Rossi, Sabrina; Ricci, Riccardo; Martini, Maurizio; Larocca, Mario; Dipasquale, Angelo; Quirino, Michela; Schinzari, Giovanni; Basso, Michele; D’Argento, Ettore; Strippoli, Antonia; Barone, Carlo; Cassano, Alessandra

    2016-01-01

    Abstract Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-α genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-α mutation (n. 2) and exon 18 PDGFR-α mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID:27661019

  18. LAPAROSCOPIC RESECTION OF GASTROINTESTINAL STROMAL TUMORS (GIST)

    PubMed Central

    LOUREIRO, Marcelo de Paula; de ALMEIDA, Rômulo Augusto Andrade; CLAUS, Christiano Marlo Paggi; BONIN, Eduardo Aimoré; CURY-FILHO,, Antônio Moris; DIMBARRE, Daniellson; da COSTA, Marco Aurélio Raeder; VITAL, Marcílio Lisboa

    2016-01-01

    Background Gastrointestinal mesenchymal or stromal tumors (GIST) are lesions originated on digestive tract walls, which are treated by surgical resection. Several laparoscopic techniques, from gastrectomies to segmental resections, have been used successfully. Aim Describe a single center experience on laparoscopic GIST resection. Method Charts of 15 operated patients were retrospectively reviewed. Thirteen had gastric lesions, of which ten were sub epithelial, ranging from 2-8 cm; and three were pure exofitic growing lesions. The remaining two patients had small bowel lesions. Surgical laparoscopic treatment consisted of two distal gastrectomies, 11 wedge gastric resections and two segmental enterectomies. Mechanical suture was used in the majority of patients except on six, which underwent resection and closure using manual absorbable sutures. There were no conversions to open technique. Results Mean operative time was 1h 29 min±92 (40-420 min). Average lenght of hospital stay was three days (2-6 days). There were no leaks, postoperative bleeding or need for reintervention. Mean postoperative follow-up was 38±17 months (6-60 months). Three patients underwent adjuvant Imatinib treatment, one for recurrence five months postoperatively and two for tumors with moderate risk for recurrence . Conclusion Laparoscopic GIST resection, not only for small lesions but also for tumors above 5 cm, is safe and acceptable technique. PMID:27120729

  19. Giant gastrointestinal stromal tumor of the stomach.

    PubMed

    Ionescu, Sever; Barbu, Emil; Ionescu, Călin; Costache, Adrian; Bălăşoiu, Maria

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the digestive tract. Gastric localization is the most frequent. The aim of this study is to evaluate the importance of immunohistochemical factors (CD117, CD34, α-SMA, vimentin, p53, Ki67) in diagnostic and size tumor and mitotic activity as prognostic factors for these tumors. We present the case of a 66-year-old male patient with a giant gastric GIST. Like in the vast majority, the symptomatology in this patient has long been faint, despite the large tumor size, and when it became manifest, it was nonspecific. Imagery wise, the computer tomography (CT) scan was the most efficient, showing the origin of the tumor from the greater curvature of the stomach, its dimensions, as well as the relations with the other abdominal viscera. Surgery in this patient was en-bloc, according to the principles of GIST. The histological aspect is characterized by a proliferation of spindle cells positive for CD117 and CD34. Despite complete microscopic resection, the size of the tumor (25×20×27 cm) and the mitotic activity (21÷5 mm2) remains important relapse factor.

  20. Intestinal gastrointestinal stromal tumor in a cat

    PubMed Central

    SUWA, Akihisa; SHIMODA, Tetsuya

    2017-01-01

    A 12-year-old, 3.6-kg, spayed female domestic shorthaired cat had a 2-month history of anorexia and weight loss. Abdominal ultrasonography and computed tomography revealed an exophytic mass originating from the jejunum with very poor central and poor peripheral contrast enhancement. On day 14, surgical resection of the jejunum and mass with 5-cm margins and an end-to-end anastomosis were performed. Histopathological examination revealed the mass was a transmural, invasive cancer showing exophytic growth and originating from the small intestinal muscle layer. Immunohistochemical analysis of tumor cells revealed diffuse positivity for KIT protein and negativity for desmin and S-100. The mass was diagnosed as a gastrointestinal stromal tumor (GIST). Ultrasonographic findings indicated the tumor probably metastasized to the liver and omentum, as seen in humans and dogs. The owner rejected further treatment at the last visit on day 192. To our knowledge, this is the first report of intestinal tumor and metastasis in feline GIST and its imaging features. PMID:28163271

  1. Atypical presentation of gastrointestinal stromal tumours-a case report.

    PubMed

    Raja, Kalpana; Dev, Bhawna; Santosham, Roy; Santhosh, Joseph

    2013-06-01

    Gastrointestinal stromal tumors (GISTs) are benign mesenchymal tumors of the gastrointestinal tract (GIT). Their clinical presentations are variable. We report a case of a 31-year-old man who presented with pain in the abdomen and vomiting. CT abdomen revealed a large exophytic mass in the epigastrium with enhancement pattern similar to hemangioma. No relationship of the mass could be made out with the adjacent structures on CT, histopathology proved it to be a GIST.

  2. Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal tumors.

    PubMed

    Smith, Stephen M; Coleman, Joshua; Bridge, Julia A; Iwenofu, O Hans

    2015-04-01

    Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin with over fifty subtypes. The use of hematoxylin and eosin stained sections (and immunohistochemistry) in the morphologic assessment of these tumors has been the bane of clinical diagnosis until recently. The last decade has witnessed considerable progress in the understanding and application of molecular techniques in refining the current understanding of soft tissue sarcomas and gastrointestinal stromal tumors beyond the limits of traditional approaches. Indeed, the identification of reciprocal chromosomal translocations and fusion genes in some subsets of sarcomas with potential implications in the pathogenesis, diagnosis and treatment has been revolutionary. The era of molecular targeted therapy presents a platform that continues to drive biomarker discovery and personalized medicine in soft tissue sarcomas and gastrointestinal stromal tumors. In this review, we highlight how the different molecular techniques have enhanced the diagnosis of these tumors with prognostic and therapeutic implications.

  3. Meckel Diverticulum Harboring a Rare Gastrointestinal Stromal Tumor

    PubMed Central

    Berry, Andrew C.; Nakshabendi, Rahman; Kanar, Ozdemir; Hamer, Sean

    2017-01-01

    Background: Tumors within a Meckel diverticulum are a rare complication observed in only 0.5%-3.2% of symptomatic cases. The majority of tumors are benign, but some malignant tumors, such as gastrointestinal stromal tumors (GISTs) can occur. Case Report: We report the case of a 48-year-old female who presented with severe abdominal pain and nausea and was found to have a GIST arising from a Meckel diverticulum. Conclusion: The differential diagnosis of a pelvic mass in a middle-aged female presenting with gastrointestinal symptoms must remain broad. With an atypical presentation site, distinguishing benign tumors from malignant tumors such as GISTs is of paramount importance. PMID:28331460

  4. [Gastrointestinal stromal tumors: case reports and review of the literature].

    PubMed

    Bronzino, P; Colombini, M; Ferro, A; Gambetta, G; Gennaro, M; Ivaldi, L; Revetria, P

    2008-01-01

    The Authors describe four cases of gastrointestinal stromal tumours (GIST) two of them were localized in the stomach, the others in the ileum. GIST are neoplasms of mesenchymal origin which develop inside the wall of the digestive tract. The most frequent site is the stomach, followed by the small bowel; less commonly these tumors can affect the oesophagus, the colon and the rectum. GIST originate from precursors of the interstitial cells of Cajal, which are localized in the gastro-intestinal wall and are involved in the regulation of the peristalsis. The treatment is surgical resection. For advanced disease there is a new interesting treatment based on the imatinib, a tyrosine kinase inhibitor.

  5. Diagnosis and treatment of gastrointestinal stromal tumor extending to prostate

    PubMed Central

    Xu, Huan; Liu, Chong; Chen, Yanbo; Gu, Meng; Cai, Zhikang; Chen, Qi; Wang, Zhong

    2016-01-01

    Abstract Rationale: Gastrointestinal stromal tumor (GIST) is the neoplasm of gastrointestinal tract. Patient concerns: The patient complained about the retention of urinary. Diagnoses: GIST. Interventions: radical prostatectomy and the imatinib therapy. Outcomes: No recurrence and metastasis have been found during a 14-month follow-up. Lessons: comprehensive treatment is necessary for the GIST treatment. Furthermore, we summarize a review of the literature of GIST occurring in the prostate gland treated by different methods and 4 kinds of rare diseases in prostate. PMID:27861390

  6. Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers

    ClinicalTrials.gov

    2012-05-24

    Gastrointestinal Neoplasms; Gynecologic Cancers; Gynecologic Cancers Cervical Cancer; Gastric (Stomach) Cancer; Gastro-Esophageal(GE) Junction Cancer; Gastrointenstinal Stromal Tumor (GIST); Colon/Rectal Cancer; Colon/Rectal Cancer Colon Cancer; Colon/Rectal Cancer Rectal Cancer; Colon/Rectal Cancer Anal Cancer; Anal Cancer; Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Pancreatic Cancer

  7. Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult

    PubMed Central

    Yamamoto, Mami; Yamamoto, Kentaroh; Taketomi, Hirotaka; Yamamoto, Fumio; Yamamoto, Hiroshi

    2016-01-01

    The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth. PMID:27920659

  8. Gastrointestinal Stromal Tumor Arising From a Gastric Duplication Cyst

    PubMed Central

    Machicado, Jorge; Davogustto, Giovanni

    2016-01-01

    Gastric duplication cysts (GDC) are rarely diagnosed in adults, but previous cases have been associated with malignancy. We present a case of gastrointestinal stromal tumor (GIST) arising from a GDC in a 71-year-old woman who presented with 3 years of early satiety, anorexia, abdominal distention, and weight loss. Abdominal CT showed a 9.3 x 5.2 x 9.5-cm well-circumscribed cystic mass arising 3 cm above the gastroduodenal junction. The cyst was resected, and histopathology was consistent with GDC. Future studies are needed to clarify the malignant potential of GDC and the molecular pathways for its development. PMID:27144196

  9. Primary gastrointestinal stromal tumor of the liver: A case report

    PubMed Central

    Luo, Xiao-Li; Liu, Dan; Yang, Jian-Jun; Zheng, Min-Wen; Zhang, Jing; Zhou, Xiao-Dong

    2009-01-01

    We report a case of primary gastrointestinal stromal tumor (GIST) of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound (CEUS) revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography (CT) showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CD117. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT. PMID:19653356

  10. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    PubMed Central

    Sarsenov, Dauren; Tırnaksız, Mehmet Bülent; Doğrul, Ahmet Bülent; Tanas, Özlem; Gedikoglu, Gökhan; Abbasoğlu, Osman

    2015-01-01

    Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor. PMID:25785332

  11. Mesenteric gastrointestinal stromal tumour presenting as intracranial space occupying lesion

    PubMed Central

    Puri, Tarun; Gunabushanam, Gowthaman; Malik, Monica; Goyal, Shikha; Das, Anup K; Julka, Pramod K; Rath, Goura K

    2006-01-01

    Background Gastrointestinal stromal tumours (GIST) usually present with non-specific gastrointestinal symptoms such as abdominal mass, pain, anorexia and bowel obstruction. Methods We report a case of a 42 year old male who presented with a solitary intracranial space occupying lesion which was established as a metastasis from a mesenteric tumour. Results The patient was initially treated as a metastatic sarcoma, but a lack of response to chemotherapy prompted testing for CD117 which returned positive. A diagnosis of mesenteric GIST presenting as solitary brain metastasis was made, and the patient was treated with imatinib. Conclusion We recommend that all sarcomas with either an intraabdominal or unknown origin be routinely tested for CD117 to rule out GIST. PMID:17105654

  12. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

    PubMed Central

    Kindblom, L. G.; Remotti, H. E.; Aldenborg, F.; Meis-Kindblom, J. M.

    1998-01-01

    The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:9588894

  13. A gist of gastrointestinal stromal tumors: A review

    PubMed Central

    Rammohan, Ashwin; Sathyanesan, Jeswanth; Rajendran, Kamalakannan; Pitchaimuthu, Anbalagan; Perumal, Senthil-Kumar; Srinivasan, UP; Ramasamy, Ravi; Palaniappan, Ravichandran; Govindan, Manoharan

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors. PMID:23847717

  14. Characteristics of gastrointestinal stromal tumours, diagnostic procedure and therapeutic management and main directions of nursing practice in gastrointestinal stromal tumours

    PubMed Central

    Głuszek, Stanisław; Kozieł, Dorota

    2014-01-01

    Gastrointestinal stromal tumours (GIST) constitute a separate group of mesenchymal neoplasms of the gastrointestinal tract. They have been commonly recognized for a few years, they have created a new problem in medical practice. GIST are more often centred in the stomach. They equally affect female and male patients and occur mainly in patients older than 50 years of age. The clinical picture of the tumour is non-specific. Radical surgical treatment and molecularly targeted therapy with tyrosine kinase inhibitors are used in GIST treatment. Nursing practice with reference to GIST danger is connected with biopsychosocial interventions of perioperative, oncological and palliative procedures and involves the area of health education mainly oriented towards shaping preventive procedures which favour early disease detection and support therapy and recovery. PMID:25784835

  15. [A rare case of bone metastasis from gastro-intestinal stromal tumour: place of radiotherapy].

    PubMed

    Heymann, S; Imperiale, A; Schlund-Schoettel, E; Sauer, B; Dourthe, L-M

    2014-01-01

    Gastro-intestinal stromal tumours are the most common mesenchymal neoplasms of the gastrointestinal tract. Their usual metastatic sites are the liver and the peritoneum, but gastro-intestinal stromal tumours rarely metastasize to the bones. We report the case of a 56-year-old male presenting with bone lesions six years after initial surgical resection. We discuss through this paper the possibilities of management of these lesions and the place of radiotherapy.

  16. Management of early asymptomatic gastrointestinal stromal tumors of the stomach

    PubMed Central

    Scherübl, Hans; Faiss, Siegbert; Knoefel, Wolfram-Trudo; Wardelmann, Eva

    2014-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cases in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultrasound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach (< 1 cm) show self-limiting tumorigenesis. Thus, early (< 1 cm) asymptomatic gastric GIST (synonym: micro-GIST) are found in 20%-30% of the elderly. The mostly elderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic surveillance. PMID:25031785

  17. Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

    PubMed

    Zińczuk, Justyna; Bandurski, Roman; Pryczynicz, Anna; Konarzewska-Duchnowska, Emilia; Kemona, Andrzej; Kędra, Bogusław

    2015-05-01

    Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions.

  18. Gastrointestinal stromal tumor in an XYY/XY male.

    PubMed

    Limacher, Jean-Marc; Girard-Lemaire, Françoise; Jeandidier, Eric; Chenard-Neu, Marie-Pierre; Kassem, Maysoun; Flori, Elisabeth; Bergerat, Jean-Pierre

    2002-03-01

    A 32-year-old patient was diagnosed with a gastrointestinal stromal tumor of the small bowel. The pathologic diagnosis was confirmed by positive immunochemistry against CD34, and against CD117, the tyrosine-kinase c-kit. We performed a karyotypic analysis on the basis of the patient's tall stature and speech difficulties. One hundred thirty-two metaphases were obtained on PHA-stimulated peripheral blood; 123 of them presented an extra chromosome Y. Fluorescence in situ hybridization using a Y satellite III probe showed the presence of a sole copy of chromosome Y in the tumor cells precluding a direct relationship between the extra chromosome Y and the initiation of the tumor. This is, to our knowledge, the second occurrence of a nonhematologic malignancy reported in this genetic disorder. A review of the malignancies observed in men with the XYY constitution is presented.

  19. Paraneoplastic Hypoglycaemia: A Rare Manifestation of Pelvic Gastrointestinal Stromal Tumour

    PubMed Central

    Hadi, Rahat; Mehrotra, Kiranpreet; Rastogi, Shivani; Masood, Shakeel

    2017-01-01

    Non-Islet Cell Tumour Induced Hypoglycaemia (NICTH), presenting with recurrent fasting hypoglycaemia is a very rare paraneoplastic syndrome. It usually presents with large metastatic mesenchymal tumours. NICTH secondary to Gastrointestinal Stromal Tumour (GIST) is even rarer. Diagnosis of NICTH is based on the low serum insulin level, low serum concentrations of Insulin Like Growth Factor (IGF-I) and IGF binding protein- III (IGFBP-III) in combination with elevated concentrations of pro-IGF-II. Various Immunohistochemical (IHC) markers are integral to diagnosis of GIST namely 2-deoxyglucose-6-phosphate phosphatase -1(DOG-1), Cluster Differentiation 34 (CD 34), Cluster Differentiation 117 (CD117). The management requires prompt intravenous hydration and glucose infusions followed by surgical resection. We hereby, report a rare case of a 65-year-old female with intractable fasting hypoglycaemia due to overproduction of "big" insulin-like growth factor II diagnosed to have pelvic GIST and managed by Steroids and Imatinib.

  20. CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

    ClinicalTrials.gov

    2013-06-03

    Gastrointestinal Stromal Tumor; Recurrent Adult Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  1. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours

    PubMed Central

    Palazzo, L; Landi, B; Cellier, C; Cuillerier, E; Roseau, G; Barbier, J

    2000-01-01

    BACKGROUND/AIM—Some endoscopic ultrasonographic (EUS) features have been reported to be suggestive of malignancy in gastrointestinal stromal cell tumours (SCTs). The aim of this study was to assess the predictive value of these features for malignancy.
METHODS—A total of 56 histologically proven cases of SCT studied by EUS between 1989 and 1996 were reviewed. There were 42 gastric tumours, 12 oesophageal tumours, and two rectal tumours. The tumours were divided into two groups: (a) benign SCT, comprising benign leiomyoma (n = 34); (b) malignant or borderline SCT (n = 22), comprising leiomyosarcoma (n = 9), leiomyoblastoma (n = 9), and leiomyoma of uncertain malignant potential (n = 4). The main EUS features recorded were tumour size, ulceration, echo pattern, cystic spaces, extraluminal margins, and lymph nodes with a malignant pattern. The two groups were compared by univariate and multivariate analysis.
RESULTS—Irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern were most predictive of malignant or borderline SCT. Pairwise combinations of the three features had a specificity and positive predictive value of 100% for malignant or borderline SCT, but a sensitivity of only 23%. The presence of at least one of these three criteria had 91% sensitivity, 88% specificity, and 83% predictive positive value. In multivariate analysis, cystic spaces and irregular margins were the only two features independently predictive of malignant potential. The features most predictive of benign SCTs were regular margins, tumour size ⩽30 mm, and a homogeneous echo pattern. When the three features were combined, histology confirmed a benign SCT in all cases.
CONCLUSIONS—The combined presence of two out of three EUS features (irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern) had a positive predictive value of 100% for malignant or borderline gastrointestinal SCT. Tumours less than 30

  2. Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour.

    PubMed

    Wachter, Nicolas; Wörns, Marcus-Alexander; Dos Santos, Daniel Pinto; Lang, Hauke; Huber, Tobias; Kneist, Werner

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology-controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve-sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs.

  3. Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour

    PubMed Central

    Wachter, Nicolas; Wörns, Marcus-Alexander; dos Santos, Daniel Pinto; Lang, Hauke; Huber, Tobias; Kneist, Werner

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology-controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve-sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs. PMID:27279406

  4. CT Features of Colorectal Schwannomas: Differentiation from Gastrointestinal Stromal Tumors

    PubMed Central

    Kang, Ji Hee; Kim, Se Hyung; Kim, Young Hoon; Rha, Sung Eun; Hur, Bo Yun; Han, Joon Koo

    2016-01-01

    Purpose To find differential CT features of colorectal schwannomas from gastrointestinal stromal tumors (GISTs). Materials and Methods CT features of 13 pathologically proven colorectal schwannomas and 21 GISTs were retrospectively reviewed. The following CT items were analyzed: size, longitudinal and transverse location, shape, margin, homogeneity, necrosis, surface ulceration, calcification, degree of attenuation, the presence of enlarged lymph node (LN), and metastasis. Among the features, significant variables were evaluated using univariate statistical tests. The optimal cut-off point of tumor size was obtained by ROC analysis. Binary logistic regression analysis was used to find the most independent CT variables. Results Small size, non-rectum location, smooth margin, homogeneous high attenuation without necrosis, and the presence of enlarged LNs were found to be significant variables to differentiate schwannomas from GISTs (P<0.05). The optimized cut-off point for tumor size in distinguishing GISTs from schwannomas was 3.9 cm (AUC = 0.808, sensitivity = 66.7%, specificity = 92.3%, P<0.0001). Binary regression analysis revealed that only non-rectum location remained independent predictor for schwannomas differentiated from GISTs (odds ratio = 31.667, P = 0.001). Conclusion Colorectal schwannomas usually located in non-rectum and appear as small subepithelial nodules showing homogeneous high attenuation and smooth margin. Schwannomas exclusively accompany with enlarged LNs. PMID:28005903

  5. [Gastrointestinal stromal tumors (GIST): at the forefront of targeted therapies].

    PubMed

    Emile, Jean-François

    2013-01-01

    Although gastrointestinal stromal tumors (GIST) are the most frequent sarcomas, they were usually not diagnosed before 1998. GIST derive from interstitial cells of Cajal, and may develop along the digestive tract, mainly from stomach and small intestine. GIST are characterized by the expression of KIT (CD117), and mutations KIT or PDGFRA are present in 85 % of cases. More than 150 different types of mutations have been reported. They are responsible for a constitutive activation of these tyrosine kinase receptors, in absence of their specific ligand. Detection of these mutations may help to confirm the diagnosis or to evaluate the prognosis. The mutations also have a predictive value. Indeed patients with metastatic GIST and duplication within exon 9 of KIT deserve to receive twice the dose of imatinib, while GIST with PDGFRA p.D842 V mutation are resistant to this drug. This review presents the main characteristics of GIST, and focus on the important insights of studies on GIST and their cell models in the field of oncology.

  6. Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas.

    PubMed

    Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing

    2013-03-28

    Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

  7. Liquid biopsy in gastrointestinal stromal tumors: a novel approach.

    PubMed

    Nannini, Margherita; Astolfi, Annalisa; Urbini, Milena; Biasco, Guido; Pantaleo, Maria A

    2014-08-14

    The role of molecular analysis in the management of gastrointestinal stromal tumors (GIST) remains indisputable. To date, tumor tissue extracted from specimens obtained by surgical or biopsy procedures has been the only source of the tumor DNA required for the molecular and genomic assessment of cancer. However, tumor tissue sampling has several clinical limitations: for example, the invasiveness of these procedures precludes repeated sampling. Thus, it is possible to obtain only a static molecular picture of the disease, a picture that lacks the inter- and intra-metastatic molecular heterogeneity that characterizes most GIST. In contrast, circulating tumor DNA obtained from a patient's bloodstream, known as liquid biopsy, can theoretically overcome the limitations of tissue biopsies and provide the same molecular and genomic information. GIST are recognized as a paradigm of molecular biology among solid tumors. Although few but promising data on liquid biopsy in GIST have been accumulated to date, these tumors may provide the optimal field for application of this challenging approach.

  8. Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells.

    PubMed

    Bauer, Sebastian; Parry, Joshua A; Mühlenberg, Thomas; Brown, Matthew F; Seneviratne, Danushka; Chatterjee, Payel; Chin, Anna; Rubin, Brian P; Kuan, Shih-Fan; Fletcher, Jonathan A; Duensing, Stefan; Duensing, Anette

    2010-01-01

    Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes. Although >85% of GIST patients treated with the small-molecule inhibitor imatinib mesylate (Gleevec) achieve disease stabilization, complete remissions are rare and a substantial proportion of patients develop resistance to imatinib over time. Upregulation of soluble, non-chromatin-bound histone H2AX has an important role in imatinib-induced apoptosis of GIST cells. Additionally, H2AX levels in untreated GIST are maintained at low levels by a pathway that involves KIT, phosphoinositide 3-kinase, and the ubiquitin-proteasome system. In this study, we asked whether bortezomib-mediated inhibition of the ubiquitin-proteasome machinery could lead to upregulation of histone H2AX and GIST cell death. We show that bortezomib rapidly triggers apoptosis in GIST cells through a combination of mechanisms involving H2AX upregulation and loss of KIT protein expression. Downregulation of KIT transcription was an underlying mechanism for bortezomib-mediated inhibition of KIT expression. In contrast, the nuclear factor-kappaB signaling pathway did not seem to play a major role in bortezomib-induced GIST cell death. Significantly, we found that bortezomib would induce apoptosis in two imatinib-resistant GIST cell lines as well as a short-term culture established from a primary imatinib-resistant GIST. Collectively, our results provide a rationale to test the efficacy of bortezomib in GIST patients with imatinib-sensitive or -resistant tumors.

  9. Incidental detection of a bleeding gastrointestinal stromal tumor on Tc-99m red blood cell scintigraphy.

    PubMed

    Santhosh, Sampath; Bhattacharya, Anish; Gupta, Vikas; Singh, Rajinder; Radotra, Bishan Dass; Mittal, Bhagwant Rai

    2012-10-01

    The role of 99m-technetium labeled red blood cell (RBC) scintigraphy in acute gastro-intestinal bleed is well-established. The authors report a case of a bleeding gastrointestinal stromal tumor (GIST) incidentally discovered on Tc-99m RBC scintigraphy.

  10. Diagnostic and treatment strategy for small gastrointestinal stromal tumors

    PubMed Central

    Goto, Osamu; Raut, Chandrajit Premanand; Yahagi, Naohisa

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini‐GISTs) (1‐2 cm) and pathologic GISTs (micro‐GISTs) (<1 cm) are frequently reported. Most mini‐GISTs and almost all micro‐GISTs of the stomach may exhibit benign clinical behavior, and only mini‐GISTs with high‐risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini‐GISTs with high‐risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow‐up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal and colorectal GISTs, surgery is indicated irrespective of size because of their greater malignant potential. Otherwise, mini‐GISTs without high‐risk features, micro‐GISTs, and small submucosal tumors measuring <5 cm without high‐risk features may be followed by periodical endoscopic ultrasonography. Although surgical approaches and operative methods are selected according to tumor size, location, growth pattern, and surgical teams, laparoscopic surgery has produced similar oncologic outcomes and is less invasiveness compared with open surgery. After resection, pathologic examination for diagnosis and risk assessment is mandatory, and genotyping is also recommended for high‐risk GISTs. Endoscopic resection techniques, although feasible, are not routinely indicated for most mini‐GISTs or micro‐GISTs. Cancer 2016;122:3110–8. © 2016 The Authors

  11. Recurrent epimutation of SDHC in gastrointestinal stromal tumors.

    PubMed

    Killian, J Keith; Miettinen, Markku; Walker, Robert L; Wang, Yonghong; Zhu, Yuelin Jack; Waterfall, Joshua J; Noyes, Natalia; Retnakumar, Parvathy; Yang, Zhiming; Smith, William I; Killian, M Scott; Lau, C Christopher; Pineda, Marbin; Walling, Jennifer; Stevenson, Holly; Smith, Carly; Wang, Zengfeng; Lasota, Jerzy; Kim, Su Young; Boikos, Sosipatros A; Helman, Lee J; Meltzer, Paul S

    2014-12-24

    Succinate dehydrogenase (SDH) is a conserved effector of cellular metabolism and energy production, and loss of SDH function is a driver mechanism in several cancers. SDH-deficient gastrointestinal stromal tumors (dSDH GISTs) collectively manifest similar phenotypes, including hypermethylated epigenomic signatures, tendency to occur in pediatric patients, and lack of KIT/PDGFRA mutations. dSDH GISTs often harbor deleterious mutations in SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx), but some are SDHx wild type (WT). To further elucidate mechanisms of SDH deactivation in SDHx-WT GIST, we performed targeted exome sequencing on 59 dSDH GISTs to identify 43 SDHx-mutant and 16 SDHx-WT cases. Genome-wide DNA methylation and expression profiling exposed SDHC promoter-specific CpG island hypermethylation and gene silencing in SDHx-WT dSDH GISTs [15 of 16 cases (94%)]. Six of 15 SDHC-epimutant GISTs occurred in the setting of the multitumor syndrome Carney triad. We observed neither SDHB promoter hypermethylation nor large deletions on chromosome 1q in any SDHx-WT cases. Deep genome sequencing of a 130-kbp (kilo-base pair) window around SDHC revealed no recognizable sequence anomalies in SDHC-epimutant tumors. More than 2000 benign and tumor reference tissues, including stem cells and malignancies with a hypermethylator epigenotype, exhibit solely a non-epimutant SDHC promoter. Mosaic constitutional SDHC promoter hypermethylation in blood and saliva from patients with SDHC-epimutant GIST implicates a postzygotic mechanism in the establishment and maintenance of SDHC epimutation. The discovery of SDHC epimutation provides a unifying explanation for the pathogenesis of dSDH GIST, whereby loss of SDH function stems from either SDHx mutation or SDHC epimutation.

  12. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  13. Large gastrointestinal stromal tumours of the stomach: Is laparoscopy reasonable?

    PubMed Central

    Severino, Beatrice Ulloa; Fuks, David; Lainas, Panagiotis; Blain, Antoine; Validire, Pierre; Ferraz, Jean-Marc; Perniceni, Thierry; Gayet, Brice

    2016-01-01

    BACKGROUND: Laparoscopic resection (LR) offers significant advantages compared to open resections for gastric gastrointestinal stromal tumours (GISTs). We aimed to evaluate whether LR outcomes jeopardised short and long-term outcomes of patients with large GISTs. PATIENTS AND METHODS: Among 50 patients undergoing surgery for gastric GISTs, 12 underwent LR for large GISTs (>5 cm). Their characteristics, perioperative results and survival were retrospectively compared to those of 22 patients who underwent LR for ‘small GIST’. RESULTS: The two groups were similar regarding demographics, rate of wedge resection and mean blood loss. No patient required transfusion or conversion. Operative time was significantly increased in the ‘large GIST’ group (160 min vs 112 min, P = 0.001). Mean tumour size was significantly lower in the ‘small GIST’ group (8.4 cm vs 2.4 cm, P = 0.0001). Resection margins were negative. The mortality rate was nil and the overall morbidity rates was similar in both groups. Median length of hospital stay was significantly increased in the ‘large GIST’ group (7 days vs 5 days, P = 0.004). Median follow-up was 47 months and one patient in the ‘small GIST’ group developed recurrence and died during follow-up 11 years after surgery. No patient died during follow-up. CONCLUSIONS: LR for large GISTs is safe and technically feasible and does not negatively influence the oncologic course. Prospective randomised trials should be performed before using this approach in routine surgical care. PMID:27073308

  14. Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

    PubMed

    O'Brien, Katie M; Orlow, Irene; Antonescu, Cristina R; Ballman, Karla; McCall, Linda; DeMatteo, Ronald; Engel, Lawrence S

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT). Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836) and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836). CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively). Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic origins and

  15. Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST).

    PubMed

    Cameron, Silke; Gieselmann, Marieke; Blaschke, Martina; Ramadori, Giuliano; Füzesi, Laszlo

    2014-01-01

    We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites.

  16. Gastrointestinal Stromal Tumors, Somatic Mutations and Candidate Genetic Risk Variants

    PubMed Central

    O'Brien, Katie M.; Orlow, Irene; Antonescu, Cristina R.; Ballman, Karla; McCall, Linda; DeMatteo, Ronald; Engel, Lawrence S.

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or “signatures” in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT). Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836) and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836). CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively). Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic origins

  17. Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer

    PubMed Central

    McCoy, M J; Hemmings, C; Miller, T J; Austin, S J; Bulsara, M K; Zeps, N; Nowak, A K; Lake, R A; Platell, C F

    2015-01-01

    Background: Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown. Methods: Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated. Results: Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade. Conclusions: Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer. PMID:26645238

  18. Massive lower gastrointestinal bleeding associated with solitary rectal ulcer in a patient with Behçet's disease.

    PubMed

    Bes, C; Dağlı, Ü; Yılmaz, F; Soy, M

    2015-09-16

    Solitary rectal ulcer syndrome is a rare benign disorder that has a wide range of clinical presentations and variable endoscopic findings which makes it difficult to diagnose and treat. The clinical and endoscopic picture in this condition can also mimic malign ulceration, malignancy or Crohn's disease. Behçet's disease can affect the gastrointestinal tract. However to the best of our knowledge, no case with solitary rectal ulceration has been reported so far in literature. We herein present a patient diagnosed with Behçet's disease admitted to our clinic with rectal bleeding due to solitary rectal ulceration.

  19. Lichenoid drug eruption caused by imatinib mesylate in a Chinese patient with gastrointestinal stromal tumor.

    PubMed

    Luo, Jing-Ru; Xiang, Xiao-Jun; Xiong, Jian-Ping

    2016-09-01

    Imatinib mesylate, the first agent approved for the treatment of unresectable or metastatic gastrointestinal stromal tumor, is a tyrosine kinase inhibitor targeting (KIT) and the platelet-derived growth factor receptor-α and -β. However, imatinib administration can be accompanied by various adverse events. Here we report a case of Lichenoid drug eruption (LDE) that appeared 24 weeks after commencement of imatinib in a 73-year-old man with gastrointestinal stromal tumor (GIST). The skin lesions were distributed over his face, trunk and limbs, which improved only after discontinuation of imatinib therapy. To the best of our knowledge, this is the first report of imatinib-induced LDE in the Chinese population.

  20. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  1. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    PubMed

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-02-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

  2. [Gastrointestinal stromal tumors: report of a clinical case and review of the literature].

    PubMed

    Bronzino, P; Cassinelli, G; Arena, E; Rassu, P C; Partipilo, F; Rusca, I; Cuneo, A E; Casaccia, M

    2002-01-01

    In this case report, the Authors describe a case of stromal gastric tumour, in a male 65 years old, who presented gastrointestinal bleeding. Gastro-Intestinal Stromal Tumors (GISTs) are neoplasm with an incidence of 1-3 per cent of the digestive tract malignant neoplasms. The rarity of this disease, its visceral wall localization, the histopathological characteristics make the diagnosis difficult. Moreover there is no correlation between the behaviour of these neoplasms and the histologic features. Surgery represents the main treatment for GISTs based on complete resection, followed by a long-term follow-up. Chemotherapy and radiotherapy don't seem to play a crucial role in the treatment of these neoplasms. A new treatment with inhibitors of the tyrosinekinase is under discussion. Follow-up represents the only way to evaluate the effective behaviour of the disease, due to the lack of classic prognostic factors impact.

  3. Incidental detection of gastrointestinal stromal tumor by Tc-99m MDP bone scan.

    PubMed

    Shepherd, Timothy M; Idakoji, Ibrahim A; Pampaloni, Miguel H

    2012-02-01

    This case demonstrates extraosseous 99m-technetium methylene diphosphonate (Tc-99m MDP) accumulation from a gastrointestinal stromal tumor. A 75-year-old woman underwent a temporal bone CT for conductive hearing loss that showed sclerosis in the right occipital condyle. Follow-up Tc-99m MDP bone scan for osseous metastases instead showed a mass-like extraosseous accumulation of Tc-99m MDP in the anterior left upper quadrant. Differential diagnoses included gastric cancer, lymphoma, metastatic melanoma, systemic hypercalcemia, or heterotopic mesenteric ossification. Contrast CT showed a well-circumscribed mass arising from the stomach, and subsequent pathology confirmed gastrointestinal stromal tumor. These tumors rarely can contain osteoclast-like giant cells and should be considered for extraosseous Tc-99m MDP accumulation.

  4. Small gastrointestinal stromal tumor in the stomach: identification of precursor for clinical gastrointestinal stromal tumor using c-kit and α-smooth muscle actin expression.

    PubMed

    Mikami, Tetuo; Nemoto, Yuta; Numata, Yoshiko; Hana, Kiyomi; Nakada, Norihiro; Ichinoe, Masaaki; Murakumo, Yoshiki; Okayasu, Isao

    2013-12-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. To find precursors for clinical GISTs of the stomach, small gastric stromal tumors of less than 3 cm were collected and examined immunohistochemically with analysis of the KIT mutation. Sixty-eight of 74 lesions were classified into 4 representative groups according to the expression of c-kit and α-smooth muscle actin (αSMA): group A, c-kit diffusely positive and αSMA negative (18 cases); group B, c-kit diffusely positive and αSMA focally positive (13); group C, c-kit focally positive and αSMA diffusely positive (27); and group D, c-kit negative and αSMA diffusely positive (10). Of the 4 groups, groups A and B of c-kit diffuse expression showed higher cellularity and labeling indices of p27(Kip1) and Ki-67 than did groups C and D of diffuse αSMA expression. Incidence of KIT exon 11 mutation in groups A and B was 86% (25/29), whereas that in groups C and D was 0% (0/20). Small gastric stromal tumors with c-kit diffuse expression were considered precursors for clinical GIST because they were significantly different from c-kit focally positive or negative tumors. The mutation of KIT is considered as an early event in tumorigenesis of GIST.

  5. Pancreatic extra-gastrointestinal stromal tumour masquerading as a bleeding duodenal mass

    PubMed Central

    Wegge, Jacqueline; Bartholomew, David M; Burke, Leandra H; Miller, Lisa A

    2012-01-01

    We describe a 55-year-old man presenting to our institution with a gastrointestinal bleed. He was found to have a 5 cm pancreatic extra-gastrointestinal stromal tumours (EGISTs) eroding into the duodenum and ampulla of Vater. Pancreaticoduodenectomy was performed and the tumour was noted to be positive for CD117 and CD34 with six mitotic figures per 50/high-powered field. At 5 months postoperatively he is receiving treatment with imatinib and doing well. To the best of our knowledge, our patient is only the 18th case reported in the literature to date. PMID:23087281

  6. Clinical activity of regorafenib in PDGFRA-mutated gastrointestinal stromal tumor.

    PubMed

    Grellety, Thomas; Kind, Michèle; Coindre, Jean-Michel; Italiano, Antoine

    2015-11-01

    Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal tumor of the gastrointestinal tract and one of the most frequent sarcoma. Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is crucial because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib) has become available. The most frequent PDGFRA mutation (D842V) is associated with primary resistance to imatinib. Data related to regorafenib efficacy in PDGFRA-mutated GIST are lacking. We report here a case report of a prolonged response with regorafenib in a patient with a PDGFRA-mutated GIST.

  7. Skull Metastasis of Gastric Gastrointestinal Stromal Tumor Successfully Managed by Surgery

    PubMed Central

    Park, Inkeun; Chung, Dong Hae; Yoo, Chan Jong; Shin, Dong Bok

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are rare, but are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common sites of metastasis are liver and peritoneum, while bone metastasis is rare. We report on a patient with skull metastasis after seven years of treatment with imatinib for metastatic GIST. She underwent metastasectomy consisting of craniectomy with excision of the mass, and cranioplasty and continued treatment with imatinib and sunitinib, without evidence of cranial recurrence. She died of pneumonia sepsis one year after metastasectomy. Skull metastasis of GIST is a very rare presentation, and an aggressive multidisciplinary approach should be considered whenever possible. PMID:28061498

  8. Gastrointestinal Stromal Tumor Showing Intense Tracer Uptake on PSMA PET/CT.

    PubMed

    Noto, Benjamin; Weckesser, Matthias; Buerke, Boris; Pixberg, Michaela; Avramovic, Nemanja

    2017-03-01

    A 70-year-old man with suspected prostate cancer was referred for Ga-PSMA-HBED-CC PET/CT (short PSMA PET/CT) for staging of tumor extent. Apart from vivid tracer uptake in the prostate gland and osseous metastasis, PSMA PET/CT revealed a large soft tissue mass with calcifications in the left upper abdomen showing intense tracer uptake. Histologic examination revealed the mass to be a gastrointestinal stromal tumor.

  9. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature

    PubMed Central

    Cheng, Xiaobin; Chen, Dong; Chen, Wenbin; Sheng, Qinsong

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered. PMID:27698856

  10. Management of gastrointestinal stromal tumours of limited size: proposals from a French panel of physicians.

    PubMed

    Landi, Bruno; Bouché, Olivier; Guimbaud, Rosine; Aparicio, Thomas; Berger, Anne; Bonvalot, Sylvie; Buecher, Bruno; Blay, Jean-Yves; Boustière, Christian; Coindre, Jean-Marie; Emile, Jean-François; Giovannini, Marc; Lecomte, Thierry; Le Cesne, Axel; Monges, Geneviève; Napoléon, Bertrand; Palazzo, Laurent; Chayvialle, Jean-Alain

    2011-12-01

    A number of guidelines on the management of gastro-intestinal stromal tumours (GISTs) have been published, mostly based on expert consensus. However, these guidelines have generally failed to address the specific problem of GISTs of limited size (i.e. those measuring a few centimetres in diameter) with which gastroenterologists are increasingly confronted. The aim of the present work was to draw up proposals for the diagnosis and treatment of GISTs measuring less than 5 cm in diameter. For this purpose, a number of practical questions were put to a panel of French experts.

  11. Gastric gastrointestinal stromal tumor (GIST) incidentally found and resected during laparoscopic sleeve gastrectomy.

    PubMed

    Beltran, Marcelo A; Pujado, Blazenko; Méndez, Pedro E; Gonzáles, Francisco J; Margulis, David I; Contreras, Mario A; Cruces, Karina S

    2010-03-01

    The incidence of incidental pathology found during laparoscopic bariatric surgery has been estimated to be around 2%, and gastric gastrointestinal stromal tumors (GISTs) have been found in 0.8% of patients, constituting a rather uncommon finding. Safe laparoscopic resection of gastric GISTs is an established procedure and has been described associated to gastric Roux-en-Y bypass for morbid obesity. We discuss one case of a gastric GIST incidentally discovered during laparoscopic sleeve gastrectomy for morbid obesity. The procedure was performed via laparoscopy, and the patient recovered without any complication. Currently, the patient has lost weight according to what was expected, is asymptomatic, and free of disease.

  12. Current Concepts in Non-Gastrointestinal Stromal Tumor Soft Tissue Sarcomas: A Primer for Radiologists

    PubMed Central

    Jagannathan, Jyothi P.; O'Neill, Ailbhe; Tirumani, Harika; Tirumani, Sree Harsha

    2017-01-01

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist. PMID:28096721

  13. Gastrointestinal stromal tumors of the stomach with extensive calcification: report of two cases.

    PubMed

    Kim, Hyun-Soo; Sung, Ji-Youn; Park, Won Seo; Kim, Youn Wha

    2012-01-01

    Gastrointestinal stromal tumors (GISTs) can present with focal calcification. However, the presence of extensive calcification that constitutes the major portion of a GIST is extremely rare and can be associated with diagnostic pitfalls. We herein present the first two cases of rare gastric GIST with predominantly calcified components that mimicked pancreatic solid and pseudopapillary neoplasms with extensive calcification. In patients presenting with hyper-dense, heavily calcified masses in the abdominal cavity, the possibility of GIST should be considered in the differential diagnosis. A careful search for cellular areas and the judicious application of immunostaining will thus make it possible to make a correct diagnosis.

  14. Imatinib-induced Ototoxicity in a Patient with Gastrointestinal Stromal Tumor (GIST)

    PubMed Central

    Wasif, Komal; Wasif, Nawal

    2016-01-01

    Imatinib (Gleevec) is a biological agent that is approved for the treatment of chronic myeloid leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most frequently seen adverse effects in patients treated with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, abdominal pain, and joint pain. Ototoxicity has rarely been reported except in two cases. We report a case of bilateral irreversible sensorineural hearing loss (SNHL) caused by imatinib in a patient receiving this agent in the adjuvant setting. This case underlines the importance of early recognition of this potential toxicity that can impact the quality of life. PMID:27909636

  15. Gastrointestinal Stromal Tumour with Synchronous Bone Metastases: A Case Report and Literature Review

    PubMed Central

    Rochigneux, Philippe; Mescam-Mancini, Lénaig; Perrot, Delphine; Bories, Erwan; Moureau-Zabotto, Laurence; Sarran, Anthony; Guiramand, Jérôme; Bertucci, François

    2017-01-01

    Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the digestive tract, derived from Cajal interstitial cells. Bone metastases are very rare, and there is no consensus regarding their treatment. Here, we present the unusual case of a 66-year-old man with a gastric GIST with synchronous bone and liver metastases, fully documented at the pathological and molecular levels with a KIT exon 11 mutation. After 9 months of imatinib, the scanner showed a 33% partial response of target lesions. We also review the literature and describe the characteristics, treatment, and outcome of all cases previously reported. PMID:28203166

  16. Spontaneous Perforation as a First Presentation of Ileal Gastrointestinal Stromal Tumour (GIST) with Synchronous Breast Sarcoma.

    PubMed

    Sharma M, Bir Kumar; Barad, Arun Kumar; Padu, Kemba; Singh K, Sridartha; Singh Th, Sudhir Chandra

    2014-05-01

    Gastrointestinal Stromal Tumours (GIST's) are the most common mesenchymal neoplasms of the gastrointestinal tract. Majority of the GISTs are asymptomatic and often diagnosis is incidental. Synchronous second malignancies have been reported in patients with GIST. We report a case of 50-year-old female presenting with features of hollow viscous perforation, found to have ileal GIST with perforations along with a synchronous breast sarcoma. GIST with spontaneous perforation as its first clinical manifestation is rare. Synchronous occurrence of an ileal GIST with a breast sarcoma is unique and deserves reporting. This case report highlights the varied nature of clinical presentation of the GIST and also stresses on the importance of extensive search for the synchronous second malignancies in the extra abdominal sites as well.

  17. Epigenetics in gastrointestinal stromal tumors: clinical implications and potential therapeutic perspectives.

    PubMed

    Sioulas, Athanasios D; Vasilatou, Diamantina; Pappa, Vasiliki; Dimitriadis, George; Triantafyllou, Konstantinos

    2013-11-01

    Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal neoplasms affecting the gastrointestinal tract. Activating mutations in either the KIT or PDGFRa gene are the principal oncogenic triggers with the former accounting for more than 80 % of cases. In the small subset of GIST that are wild type for both the aforementioned changes, other germline or somatic mutations have been identified. GIST exhibit a highly variable clinical behavior and the main prognostic determinants are tumor size, mitotic rate, and location. It is, however, strongly believed that, beyond classic genetics, additional epigenetic phenomena such as DNA hypomethylation and hypermethylation, microRNA alterations, and chromatin modifications underlie GIST tumorigenesis and influence the clinical course and response to standard treatment. This review aims to illuminate current advances in terms of epigenetics in GIST, as well as possible implications in prognosis and therapeutics.

  18. Case report of pneumatosis intestinalis secondary to sunitinib treatment for refractory gastrointestinal stromal tumor.

    PubMed

    Jarkowski, Anthony; Hare, Ryan; Francescutti, Valerie; Wilkinson, Neal; Khushalani, Nikhil

    2011-10-01

    Pneumatosis intestinalis (PI) occurs when inter-luminal air enters the bowel wall of the gastrointestinal tract via a mucosal defect. The condition is caused by numerous disease states, direct trauma, and various drugs. When PI is secondary to drug therapy, discontinuation of the offending agent results in the resolution of PI. We report on the case of a 73-year-old male with a history of refractory gastrointestinal stromal tumor experiencing PI while on sunitinib treatment. PI was noted via computed tomography (CT) scans 68 days after starting sunitinib therapy and showed near complete resolution on a follow up CT performed one month after discontinuing sunitinib. Given that a CT scan performed five months prior to the initiation of sunitinib did not show PI, lack of abdominal symptoms in our patient, and resolution of PI after discontinuing sunitinib, the cause of PI in our patient was likely due to sunitinib treatment.

  19. Familial and multiple gastrointestinal stromal tumors with fair response to a half-dose of imatinib.

    PubMed

    Bamba, Shigeki; Hirota, Seiichi; Inatomi, Osamu; Ban, Hiromitsu; Nishimura, Takashi; Shioya, Makoto; Imaeda, Hirotsugu; Nishida, Atsushi; Sasaki, Masaya; Murata, Satoshi; Andoh, Akira

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Since our first report in 1998, approximately 30 families with multiple GISTs due to a germline gain-of-function mutation of c-kit have been reported. We herein present a case of a family with multiple GISTs that have a germline c-kit mutation in exon 11 (Del-Val560) in two siblings. One of the patients showed a fair response to treatment with a half-dose of imatinib (200 mg/day). There are few reports describing the response to imatinib in familial GISTs and this drug appears to be a promising therapeutic option.

  20. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  1. Insulin-like Growth Factor (IGF) system and gastrointestinal stromal tumours (GIST): present and future.

    PubMed

    Nannini, Margherita; Biasco, Guido; Astolfi, Annalisa; Urbini, Milena; Pantaleo, Maria A

    2014-02-01

    In the last decades, the concept that Insulin-like Growth Factor (IGF) axis plays a key role in several steps of tumorigenesis, cancer growth and metastasis has been widely documented. The aberration of the IGF system has been described in many kinds of tumours, providing several lines of evidence in support of IGF receptor type 1 (IGF1R) as molecular target in cancer treatment. Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract, commonly characterized in most cases by KIT and PDGFRA gain mutations. Beyond to the well recognized KIT and PDGFRA gain mutations, in the last years other molecular aberrations have been investigated. Recently, several lines of evidence about the involvement of the IGF system in GIST have been accumulated. The aim of this review is to report all current data about the IGF system involvement in GIST, focusing on the current clinical implication and future perspectives.

  2. Gastrointestinal and Extragastrointestinal Stromal Tumors: Report of Two Cases and Review of the Literature

    PubMed Central

    Antonopoulos, Petros; Leonardou, Polytimi; Barbagiannis, Nikolaos; Alexiou, Konstantinos; Demonakou, Maria; Economou, Nikolaos

    2014-01-01

    We present two cases, one of a gastrointestinal stromal tumor (GIST) in the stomach and one of an extragastrointestinal stromal tumor (EGIST) in the hepatogastric ligament, which were discovered as incidental findings during computed tomography (CT) scans performed for other reasons. In both cases the diagnosis of the tumor was confirmed histologically and immunohistochemically. During the follow-up CT examinations these tumors proved to have a completely different natural course. The first case refers to an 82-year-old male patient with GIST of the stomach who refused to be operated and was followed by CT scans for a 4-year period. This patient did not show any significant changes in the morphology, size and density of the lesion. The second case refers to a 58-year-old female patient with EGIST of the hepatogastric ligament who presented with simultaneous liver metastases and remained healthy for 2 years after surgical resection, but developed local recurrence later. As a conclusion, both GISTs/EGISTs can be revealed as incidental findings in a CT scan performed for other purposes. Moreover, an untreated GIST located in the stomach can remain unchanged and without metastatic lesions for a long period of time, as in our case for a 4-year period. To our knowledge, this is the first report in the literature in whom a GIST was proved to remain almost unchanged for many years without any treatment, and we therefore attempt a further review of the current literature on stromal tumors. PMID:24707244

  3. Synchronous gastric gastrointestinal stromal tumor (GIST) and other primary neoplasms of gastrointestinal tract: report of two cases.

    PubMed

    Kaur, Ramneet; Bhalla, Sunita; Nundy, Samiran; Jain, Sunila

    2013-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with a malignant potential. However, uncommonly they can be associated with synchronous tumors of different histogenesis. We herein report two cases of gastric GIST with synchronous tumors. The first case is of a 50-year-old male patient who was suspected with GIST of stomach and was incidentally found to have an associated duodenal neuroendo-crine neoplasm. The second case is of a 62-year-old male who, while undergoing surgery for a primary colon adenocarcinoma, was incidentally detected to have a coexistent gastric GIST initially suspected to be a metastatic nodule. Coexistence of gastric GIST with neuroendocrine tumor is extremely rare. To the best of our knowledge this is the second case of gastric GIST coexisting with duodenal neuroendocrine tumor to be reported in the literature. Similarly, association of GIST with adenocarcinoma is uncommon. We herein analyze the pathological findings of two such cases, and we review the malignant potential of these synchronous tumors.

  4. Development of enterohepatic fistula after embolization in ileal gastrointestinal stromal tumor: a case report.

    PubMed

    Lee, Yun Ho; Koo, Ja Seol; Jung, Chang Ho; Chung, Sang Yoon; Lee, Jae Joong; Kim, Seung Young; Hyun, Jong Jin; Jung, Sung Woo; Choung, Rok Seon; Lee, Sang Woo; Choi, Jai Hyun

    2013-11-21

    Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor of the gastrointestinal tract that has been associated with the formation of fistulas to adjacent organs in few case reports. However, GIST with enterohepatic fistula has not been reported. Here we report the case of an enterohepatic fistula that occurred after embolization of a liver mass originating in the distal ileum. An 87-year-old woman was hospitalized for melena. On initial conventional endoscopy, a bleeding focus in the gastrointestinal tract was not found. Because of massive hematochezia, enteroscopy was performed through the anus. A protruding, ulcerative mass was found in the distal ileum that was suspected to be the source of the bleeding; a biopsy sample was taken. Electrocoagulation was not successful in controlling the bleeding; therefore, embolization was performed. After embolization, the patient developed a high fever and severe abdominal tenderness with rebound tenderness. Follow-up abdominopelvic computed tomography revealed an enterohepatic fistula between the liver and distal ileum. The fistula was treated surgically by segmental resection of the distal ileum and unlooping of the liver mass.

  5. Gastrointestinal stromal tumors: evolving role of the multidisciplinary team approach in management.

    PubMed

    Reichardt, Peter; Morosi, Carlo; Wardelmann, Eva; Gronchi, Alessandro

    2012-08-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract arising from mesenchymal cells. Treatment options include surgical resection and medical therapy with imatinib. A summary of National Comprehensive Cancer Network and European Society of Medical Oncology clinical practice guidelines relating to GIST management are presented here. A multidisciplinary team of physicians is essential to the successful treatment of GIST. Evidence supports multidisciplinary team management with a gastroenterologist, surgeon, medical oncologist, pathologist and radiologist. Consultations between them are recommended to ensure optimal care of patients with GIST. The role for individual core team workers is highlighted. The benefits of multidisciplinary disease management of patients include reducing recurrent disease, optimizing timing of surgery and organ preservation, prolonging survival for the patient and enhancing response to targeted therapies.

  6. Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach

    PubMed Central

    Coffey, Robert J.; Washington, Mary Kay; Corless, Christopher L.; Heinrich, Michael C.

    2007-01-01

    Ménétrier disease and gastrointestinal stromal tumors (GISTs) are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases (RTKs). In Ménétrier disease, overexpression of TGF-α, a ligand for the RTK EGFR, results in selective expansion of surface mucous cells in the body and fundus of the stomach. In GISTs, somatic mutations of the genes encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive kinase activity and neoplastic transformation of gut pacemaker cells (interstitial cells of Cajal). On the basis of the involvement of these RTKs in the pathogenesis of these disorders, Ménétrier disease patients have been effectively treated with a blocking monoclonal antibody specific for EGFR and GIST patients with KIT and PDGFRA tyrosine kinase inhibitors. PMID:17200708

  7. Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.

    PubMed

    Dumont, Amaury G; Yang, Yanwen; Reynoso, David; Katz, Daniela; Trent, Jonathan C; Hughes, Dennis P

    2012-09-01

    Gastrointestinal stromal tumors (GISTs) are driven by gain-of-function mutations of KIT or PDGFRa. The introduction of imatinib has significantly extended survival for patients. However, most patients develop resistances. Notch signaling is a conserved developmental pathway known to play a critical role in the development of several cancers, functioning as a tumor promoter or a tumor suppressor. Given that the normal progenitor cell for GIST, the interstitial cell of Cajal, has characteristics similar to those of cells of neuroendocrine origin, we hypothesized that Notch pathway impacts the biology of GIST cells. In this study, we retrovirally and pharmacologically manipulated the Notch pathway in human GIST cells. We also performed a retrospective analysis of a cohort on 15 primary tumors to determine the role of Hes1, a major target gene of Notch, as a prognostic marker for GIST. Constitutively, active intracellular domain of Notch1 (ICN1) expression potently induced growth arrest and downregulated KIT expression in vitro. Additionally, treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid caused dose-dependent upregulation of Notch1 expression and a parallel decrease in viability in these cells. Retroviral silencing of downstream targets of Notch (dominant-negative Hes1) and pharmacological inhibition of Notch activation (γ-secretase inhibition) partially rescued GIST cells from suberoylanilide hydroxamic acid treatment. GIST patients with high Hes1 mRNA levels have a significantly longer relapse-free survival. These results identify a novel anti-tumor effect of Notch1 and cross talk between the Notch and KIT pathways. Thus, activation of this pathway by treatment with histone deacetylase inhibitors is an appealing potential therapeutic strategy for GISTs. Précis: This study is the first report of the tumor suppressor effects of Notch pathway in gastrointestinal stromal tumors via a negative feedback with the oncogene KIT and may

  8. Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report

    PubMed Central

    Kubo, Naoki; Takeuchi, Nobumichi

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment (sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis. PMID:28321172

  9. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  10. Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): Clinical Implications of the Somatic and Germline DNA Analysis

    PubMed Central

    Ravegnini, Gloria; Nannini, Margherita; Sammarini, Giulia; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A.; Hrelia, Patrizia; Angelini, Sabrina

    2015-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA tyrosine kinase receptors, with their consequent constitutive activation. The gold standard therapy is imatinib that offers a good and stable response for approximately 18–36 months. However, resistance is very common and it is vital to identify new biomarkers. Up until now, there have been two main approaches with focus to characterize novel targets. On the one hand, the focus is on the tumor genome, as the final clinical outcome depends mainly from the cancer specific mutations/alterations patterns. However, the germline DNA is important as well, and it is inconceivable to think the patients response to the drug is not related to it. Therefore the aim of this review is to outline the state of the art of the personalized medicine in GIST taking into account both the tumor DNA (somatic) and the patient DNA (germline). PMID:26184165

  11. Gastrointestinal stromal tumors in kidney transplant recipients: Report of two cases and literature review.

    PubMed

    Cheung, Chi Yuen; Lo, Stanley Hok King; Chan, Ching Kit; Li, Fu Keung; Cheng, Ignatius Kum Po; Chau, Ka Foon

    2017-02-01

    Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal gastrointestinal neoplasms. However, GISTs occurring in kidney transplant recipients, including their treatment and outcome, are rarely described in literature. We hereby report two kidney transplant recipients with GISTs. Our first patient was diagnosed with high-risk epithelioid gastric GIST 2 years after kidney transplant. He received everolimus after resection and remained disease-free for 2 years before liver metastasis was confirmed. Imatinib therapy was planned but he died of fulminant pneumonia shortly. Our second patient was diagnosed with spindle cell GISTs in the mesentery 1 year after kidney transplant. Only partial response was obtained with imatinib as new lesions continued to develop. Withdrawal of cyclosporine and introduction of sirolimus resulted in complete shrinkage of existing tumors and no new lesions. He remained disease-free for more than 10 years. Combination therapy consisting of imatinib and inhibitors of mammalian target of rapamycin (mTORi) seems to be safe and effective in kidney transplant recipients. However, therapeutic drug monitoring of mTORi is essential to avoid nephrotoxicity. Further trials addressing the optimal dosage of imatinib and mTORi in kidney transplant recipients are recommended.

  12. Antitumor effects in gastrointestinal stromal tumors using photodynamic therapy with a novel glucose-conjugated chlorin.

    PubMed

    Tanaka, Mamoru; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Moriwaki, Kazuhiro; Akashi, Haruo; Taguchi, Takahiro; Hayashi, Noriyuki; Hamano, Shingo; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Joh, Takashi

    2014-04-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5,10,15,20-tetrakis [4-[β-d-glucopyranosylthio-2,3,5,6-tetrafluorophenyl]-2,3,[methano[N-methyl] iminomethano] chlorin (H(2)TFPC-SGlc), for the GIST treatment. Various photosensitizers were administered in vitro to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation and antitumor effects of these photosensitizers in vivo. In vitro, the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of H(2)TFPC-SGlc, and apoptosis mediated by PDT with H(2)TFPC-SGlc were significantly higher in GIST-T1 than in WI-38 cells. In vivo, H(2)TFPC-SGlc accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT. PDT with novel H(2)TFPC-SGlc is potentially useful for clinical applications about the treatment of GIST.

  13. Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor

    PubMed Central

    Koo, Dong-Hoe; Ryu, Min-Hee; Kim, Kyoung-Mee; Yang, Han-Kwang; Sawaki, Akira; Hirota, Seiichi; Zheng, Jie; Zhang, Bo; Tzen, Chin-Yuan; Yeh, Chun-Nan; Nishida, Toshirou; Shen, Lin; Chen, Li-Tzong; Kang, Yoon-Koo

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries. PMID:27384163

  14. Endoscopic en bloc resection of an exophytic gastrointestinal stromal tumor with suction excavation technique.

    PubMed

    Choi, Hyuk Soon; Chun, Hoon Jai; Kim, Kyoung-Oh; Kim, Eun Sun; Keum, Bora; Jeen, Yoon-Tae; Lee, Hong Sik; Kim, Chang Duck

    2016-06-21

    Here, we report the first successful endoscopic resection of an exophytic gastrointestinal stromal tumor (GIST) using a novel perforation-free suction excavation technique. A 49-year-old woman presented for further management of a gastric subepithelial tumor on the lesser curvature of the lower body, originally detected via routine upper gastrointestinal endoscopy. Abdominal computed tomography and endoscopic ultrasound showed a 4-cm extraluminally protruding mass originating from the muscularis propria layer. The patient firmly refused surgical resection owing to potential cardiac problems, and informed consent was obtained for endoscopic removal. Careful dissection and suction of the tumor was repeated until successful extraction was achieved without serosal injury. We named this procedure the suction excavation technique. The tumor's dimensions were 3.5 cm × 2.8 cm × 2.5 cm. The tumor was positive for C-KIT and CD34 by immunohistochemical staining. The mitotic count was 6/50 high-power fields. The patient was followed for 5 years without tumor recurrence. This case demonstrated the use of endoscopic resection of an exophytic GIST using the suction excavation technique as a potential therapy without surgical resection.

  15. Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): Clinical Implications of the Somatic and Germline DNA Analysis.

    PubMed

    Ravegnini, Gloria; Nannini, Margherita; Sammarini, Giulia; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A; Hrelia, Patrizia; Angelini, Sabrina

    2015-07-09

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA tyrosine kinase receptors, with their consequent constitutive activation. The gold standard therapy is imatinib that offers a good and stable response for approximately 18-36 months. However, resistance is very common and it is vital to identify new biomarkers. Up until now, there have been two main approaches with focus to characterize novel targets. On the one hand, the focus is on the tumor genome, as the final clinical outcome depends mainly from the cancer specific mutations/alterations patterns. However, the germline DNA is important as well, and it is inconceivable to think the patients response to the drug is not related to it. Therefore the aim of this review is to outline the state of the art of the personalized medicine in GIST taking into account both the tumor DNA (somatic) and the patient DNA (germline).

  16. Gastrointestinal stromal tumour masquerading as a cyst in the lesser sac

    PubMed Central

    Hamza, Ahmed Mahmoud; Ayyash, Emad Helmi; Alzafiri, Raed; Francis, Issam; Asfar, Sami

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are solid tumours of the gastrointestinal tract, mostly found in the stomach and intestine. They rarely present as cystic lesions. A 74-year-old woman referred to the hepatopancreaticobiliary unit, with 3 months history of upper abdominal discomfort. Abdominal ultrasound scan showed a large cystic lesion in the epigastric region suggestive of a pancreatic pseudocyst. The CT-scan showed a 6.6×6×6.3 cm size cyst related to the pancreas and extending to the hepatogastric omentum. Endoscopic ultrasound (EUS) scan was suggestive of a pancreatic pseudocyst. Aspirated Cyst fluid via EUS showed benign cytology with normal amylase, lipase and tumour markers (CEA, CA-19.9 and CA-125). She was referred as a case of pancreatic pseudocyst. After surgical excision, the histopathology confirmed the presence GIST in the wall of the cystic lesion. The possibility of GIST should be kept in mind in the presence of unusual features of a cyst on abdominal imaging. PMID:27469382

  17. Integrated genomic analyses identify frequent gene fusion events and VHL inactivation in gastrointestinal stromal tumors

    PubMed Central

    Sun, Choong-Hyun; Park, Inho; Lee, Seungmook; Kwon, Jekeun; Do, Ingu; Hong, Min Eui; Van Vrancken, Michael; Lee, Jeeyun; Park, Joon Oh; Cho, Jeonghee; Kim, Kyoung-Mee; Sohn, Tae Sung

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two genomes of GISTs for integrated analyses. We detected 306 somatic variants in nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome sequencing revealed 328 gene fusions, and the most frequently involved fusion events were associated with IGF2 fused to several partner genes including CCND1, FUS, and LASP1. We additionally identified three recurrent read-through fusion transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found intragenic deletions in one of three exons of the VHL gene and increased mRNAs of VEGF, PDGF-β, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link between VHL inactivation and overexpression of hypoxia-inducible factor target genes in the absence of hypoxia. We also identified copy number gain and increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy number and gene expression results to the KEGG pathways revealed activation of the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type GISTs. These observations will allow us to determine the genetic basis of GISTs and will facilitate further investigation to develop new therapeutic options. PMID:25987131

  18. Integrated genomic analyses identify frequent gene fusion events and VHL inactivation in gastrointestinal stromal tumors.

    PubMed

    Kang, Guhyun; Yun, Hongseok; Sun, Choong-Hyun; Park, Inho; Lee, Seungmook; Kwon, Jekeun; Do, Ingu; Hong, Min Eui; Van Vrancken, Michael; Lee, Jeeyun; Park, Joon Oh; Cho, Jeonghee; Kim, Kyoung-Mee; Sohn, Tae Sung

    2016-02-09

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two genomes of GISTs for integrated analyses. We detected 306 somatic variants in nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome sequencing revealed 328 gene fusions, and the most frequently involved fusion events were associated with IGF2 fused to several partner genes including CCND1, FUS, and LASP1. We additionally identified three recurrent read-through fusion transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found intragenic deletions in one of three exons of the VHL gene and increased mRNAs of VEGF, PDGF-β, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link between VHL inactivation and overexpression of hypoxia-inducible factor target genes in the absence of hypoxia. We also identified copy number gain and increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy number and gene expression results to the KEGG pathways revealed activation of the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type GISTs. These observations will allow us to determine the genetic basis of GISTs and will facilitate further investigation to develop new therapeutic options.

  19. Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives

    PubMed Central

    Mulet-Margalef, Nuria; Garcia-del-Muro, Xavier

    2016-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. In advanced setting and after progression to imatinib, the multi-targeted receptor tyrosine kinase inhibitor sunitinib has clearly demonstrated a clinical benefit in terms of response rate and progression-free survival with an acceptable toxicity profile. The recommended schedule for sunitinib administration is 50 mg per day 4 weeks ON and 2 weeks OFF; however, potential alternative schedules are also reviewed in the present article. Several biomarkers have been explored to better select candidates for sunitinib therapy, such as the value of early changes in standardized uptake value assessed by positron emission tomography with 18F-fluorodeoxyglucose, circulating biomarkers, clinical biomarkers such as the appearance of arterial hypertension during treatment that correlates with better outcomes, and the GIST genotype. GISTs with KIT mutations at exon 9 and the so-called wild-type GISTs seem to better respond to sunitinib. Nonetheless, further investigation is required to confirm these findings as well as to understand the mechanisms of sunitinib resistance such as the development of new KIT mutations or conformational changes in KIT receptor. PMID:28008275

  20. Heavily calcified gastrointestinal stromal tumors: Pathophysiology and implications of a rare clinicopathologic entity

    PubMed Central

    Salati, Massimiliano; Orsi, Giulia; Reggiani Bonetti, Luca; Di Benedetto, Fabrizio; Longo, Giuseppe; Cascinu, Stefano

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended and the patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis (longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature. PMID:28344749

  1. Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum.

    PubMed

    Sakurai, S; Hishima, T; Takazawa, Y; Sano, T; Nakajima, T; Saito, K; Morinaga, S; Fukayama, M

    2001-07-01

    Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.

  2. Evidence for Ca2+-Regulated ATP Release in Gastrointestinal Stromal Tumors

    PubMed Central

    Berglund, Erik; Berglund, David; Akcakaya, Pinar; Ghaderi, Mehran; Daré, Elisabetta; Berggren, Per-Olof; Köhler, Martin; Aspinwall, Craig A.; Lui, Weng-Onn; Zedenius, Jan; Larsson, Catharina; Bränström, Robert

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are thought to originate from the electrically active pacemaker cells of the gastrointestinal tract. Despite the presence of synaptic-like vesicles and proteins involved in cell secretion it remains unclear whether GIST cells possess regulated release mechanisms. The GIST tumor cell line GIST882 was used as a model cell system, and stimulus-release coupling was investigated by confocal microscopy of cytoplasmic free Ca2+ concentration ([Ca2+]i), flow cytometry, and luminometric measurements of extracellular ATP. We demonstrate that GIST cells have an intact intracellular Ca2+-signaling pathway that regulates ATP release. Cell viability and cell membrane integrity was preserved, excluding ATP leakage due to cell death and suggesting active ATP release. The stimulus-secretion signal transduction is at least partly dependent on Ca2+ influx since exclusion of extracellular Ca2+ diminishes the ATP release. We conclude that measurements of ATP release in GISTs may be a useful tool for dissecting the signal transduction pathway, mapping exocytotic components, and possibly for the development and evaluation of drugs. Additionally, release of ATP from GISTs may have importance for tumor tissue homeostasis and immune surveillance escape. PMID:23499741

  3. KIT exon 11 deletion-inversions represent complex mutations in gastrointestinal stromal tumors.

    PubMed

    Lasota, Jerzy; Miettinen, Markku

    2007-05-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT expression and mutational KIT activation have been documented in a majority of GISTs. Most mutations have been found in KIT juxtamembrane domain encoded by exon 11. Recently, we have identified three, complex KIT exon 11 mutations previously unreported in GISTs. These mutations consisted of several nucleotide deletions accompanied by insertions of inverted complementary DNA strand sequences. All three mutations were found in the 5' part of KIT exon 11. At the protein level, these mutations lead to the same end result: in-frame loss and insertion of a number of amino acids and could be considered examples of deletion-insertion. Although proper description of these mutations at the genomic level is a complex task and requires an individual approach, the uniform name deletion-inversion is suggested for this type of mutation, based on the present study. The frequency of deletion-inversions among KIT exon 11 mutant GISTs was estimated to be <0.5%, based on evaluation of 700 KIT exon 11 mutants. Molecular events leading to formation of deletion-inversions remain elusive and should be studied further.

  4. Fine needle aspiration biopsy of gastrointestinal stromal tumor presenting as an umbilical mass (Sister Mary Joseph's Nodule).

    PubMed

    Scudeler, Donizete; Wakely, Paul E

    2006-04-01

    The Sister Mary Joseph (SMJ) nodule is a clinical sign of metastatic cancer involving the umbilicus. The vast majority of these instances represent adenocarcinomas arising from ovarian or colorectal primaries. We present a patient who presented with ascites and the SMJ lesion that turned out to be a metastatic gastrointestinal stromal tumor after fine needle aspiration biopsy was performed. The lesion was subsequently histologically confirmed. Gastrointestinal stroma tumor involving the umbilicus is exceedingly uncommon and only rarely presents in this fashion. The cytomorphological features, differential diagnosis, and comparison with the tissue specimen are made.

  5. State of the Art in the Treatment of Gastrointestinal Stromal Tumors

    PubMed Central

    Garlipp, Benjamin; Bruns, Christiane J.

    2014-01-01

    Background Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. Summary From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. Key Message Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. Practical Implications The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment

  6. Supraclavicular lymph node metastases from malignant gastrointestinal stromal tumor of the jejunum: A case report with review of the literature

    PubMed Central

    Ma, Chi; Hao, Shao-Long; Liu, Xin-Cheng; Nin, Jin-Yao; Wu, Guo-Chang; Jiang, Li-Xin; Fancellu, Alessandro; Porcu, Alberto; Zheng, Hai-Tao

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the alimentary tract. These tumors may have different clinical and biological behaviors. Malignant forms usually spread via a hematogenous route, and lymph node metastases rarely occur. Herein, we report a patient with a jejunal GIST who developed supraclavicular lymph node metastasis. We conclude that lymphatic diffusion via the mediastinal lymphatic station to the supraclavicular lymph nodes can be a potential metastatic route for GISTs. PMID:28348499

  7. Gastric gastrointestinal stromal tumor with incomplete duplication cyst - a case with possibility of neoplasia in fetal-period malformed tissues.

    PubMed

    Lewitowicz, Piotr; Matykiewicz, Jaroslaw; Koziel, Dorota; Gluszek, Stanislaw Z; Sosnowski, Zbigniew; Horecka-Lewitowicz, Agata; Nasierowska-Guttmejer, Anna

    2015-03-01

    The coincidence of GIST and other gastric malignancies are documented well but arising GIST from congenital anomalies is still rarity in literature. To date, only a few papers have been concerned on the possibility of arising neoplasms from duplication cyst of gastrointestinal tract. There, are dominating usual cancers, neuroendocrine cancers or lymphomas but GIST has been noted only once. Here, we report a case of 73 years old female-patient with typical gastric stromal tumor comprised centrally locked an incomplete duplication cyst.

  8. Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

    PubMed Central

    Escobar, Guillermo A; Robinson, William A; Nydam, Trevor L; Heiple, Drew C; Weiss, Glen J; Buckley, Linda; Gonzalez, Rene; McCarter, Martin D

    2007-01-01

    Background Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. Case presentation A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. Conclusion Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established. PMID:17229322

  9. Comparison between air and carbon dioxide insufflation in the endoscopic submucosal excavation of gastrointestinal stromal tumors

    PubMed Central

    Shi, Wei-Bin; Wang, Zi-Hao; Qu, Chun-Ying; Zhang, Yi; Jiang, Han; Zhou, Min; Chen, Ying; Xu, Lei-Ming

    2012-01-01

    AIM: To evaluate the safety and efficacy of CO2 insufflation compared with air insufflation in the endoscopic submucosal excavation (ESE) of gastrointestinal stromal tumors. METHODS: Sixty patients were randomized to undergo endoscopic submucosal excavation, with the CO2 group (n = 30) and the air group (n = 30) undergoing CO2 insufflation and air insufflation in the ESE, respectively. The end-tidal CO2 level (pETCO2) was observed at 4 time points: at the beginning of ESE, at total removal of the tumors, at completed wound management, and 10 min after ESE. Additionally, the patients’ experience of pain at 1, 3, 6 and 24 h after the examination was registered using a visual analog scale (VAS). RESULTS: Both the CO2 group and air group were similar in mean age, sex, body mass index (all P > 0.05). There were no significant differences in PetCO2 values before and after the procedure (P > 0.05). However, the pain scores after the ESE at different time points in the CO2 group decreased significantly compared with the air group (1 h: 21.2 ± 3.4 vs 61.5 ± 1.7; 3 h: 8.5 ± 0.7 vs 42.9 ± 1.3; 6 h: 4.4 ± 1.6 vs 27.6 ± 1.2; 24 h: 2.3 ± 0.4 vs 21.4 ± 0.7, P < 0.05). Meanwhile, the percentage of VAS scores of 0 in the CO2 group after 1, 3, 6 and 24 h was significantly higher than that in the air group (60.7 ± 1.4 vs 18.9 ± 1.5, 81.5 ± 2.3 vs 20.6 ± 1.2, 89.2 ± 0.7 vs 36.8 ± 0.9, 91.3 ± 0.8 vs 63.8 ± 1.3, respectively, P < 0.05). Moreover, the condition of the CO2 group was better than that of the air group with respect to anal exsufflation. CONCLUSION: Insufflation of CO2 in the ESE of gastrointestinal stromal tumors will not cause CO2 retention and it may significantly reduce the level of pain, thus it is safe and effective. PMID:23326136

  10. Contrast-enhanced (endoscopic) ultrasound and endoscopic ultrasound elastography in gastrointestinal stromal tumors

    PubMed Central

    Ignee, Andre; Jenssen, Christian; Hocke, Michael; Dong, Yi; Wang, Wen-Ping; Cui, Xin-Wu; Woenckhaus, Matthias; Iordache, Sevastita; Saftoiu, Adrian; Schuessler, Gudrun; Dietrich, Christoph F.

    2017-01-01

    Background and Objectives: Gastrointestinal stromal tumors (GISTs) represent the largest group of subepithelial tumors (SET) of the upper gastrointestinal (GI) tract. They may show malignant behavior, in contrast to other SET. Endoscopic ultrasound (EUS) is frequently used to characterize SET. With the introduction of contrast-enhanced ultrasound (CEUS) into EUS (CE-EUS), distinct enhancement patterns can be detected. In the presented study, the characteristic features of CE-EUS in GIST are analyzed and compared with those of other SET. Materials and Methods: Consecutive patients from four centers with SET of the upper and middle GI tract were included and received endoscopic or transcutaneous CEUS. The results were compared with EUS-guided tissue acquisition, forceps biopsy, or surgical resection. Results: Forty-two out of 62 (68%) patients had SET of the stomach, 17/62 (27%) of the small intestine, 2/62 (3%) of the esophagus, and 1/62 (2%) extraintestinal. Eighty-one percent underwent surgery. Leiomyoma was found in 5/62 (8%) and GIST in 57/62 patients (92%). Thirty-nine out of 57 (68%) patients had GIST lesions in the stomach, 17/57 (30%) had GIST of the small intestine, and 1/57 (2%) patients had extraintestinal GISTs. GIST size was 62.6 ± 42.1 (16–200) mm. Hyperenhancement had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 98%, 100%, 100%, 93%, and 98% for the diagnosis of GIST. Fifty out of 57 patients with GIST (88%) showed avascular areas in the center of the lesions. Conclusion: CE-EUS and CEUS show hyperenhancement and avascular areas in a high percentage of GIST but not in leiomyoma. Thus, GIST and leiomyoma can be discriminated accurately. PMID:28218202

  11. DOG1 for the diagnosis of gastrointestinal stromal tumor (GIST): Comparison between 2 different antibodies.

    PubMed

    Lopes, Lisandro F; West, Robert B; Bacchi, Livia M; van de Rijn, Matt; Bacchi, Carlos E

    2010-07-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Discovered on GIST-1 (DOG1) is a recently described protein expressed in GISTs irrespective of mutation status. The aim of this study was to investigate the immunohistochemical expression of DOG1 using 2 different monoclonal antibodies (DOG1.1 and the commercially available K9 antibody) in 668 GIST cases and to compare the results with the expression of KIT. DOG1 and KIT expression also were studied in most human normal tissues and several nonmesenchymal and mesenchymal tumors other than GIST. KIT was expressed in 643 (96.3%) GISTs. DOG1.1 and K9 were positive in 538 (80.5%) and 642 (96.1%) GIST cases, respectively. In 25 (3.7%) KIT-negative GIST cases, DOG1 was expressed in 5 (20.0%) and 19 (76.0%) using DOG1.1 and K9 antibodies, respectively. Only 0.9% of GISTs were negative for KIT, DOG1.1, and K9. Most normal human tissues did not reveal KIT and DOG1 expression. DOG1.1 was positive in only 2 of 57 synovial sarcomas and 1 of 61 soft tissue leiomyosarcomas. K9 was positive in 5 of 57 synovial sarcomas, 1 of 14 angiosarcomas, 1 of 61 soft tissue leiomyosarcomas, 3 of 4 adenoid cystic carcinomas of the head and neck, and in myoepithelial cells of 9 of 11 fibroadenomas of the breast. In conclusion, the commercially available K9 is of great utility for the diagnosis of most KIT-negative GISTs, and the combination of both KIT and K9 antibody in a panel of immunohistochemistry can define the diagnosis of GIST in more than 99% of cases.

  12. Endoscopic submucosal dissection for silent gastric Dieulafoy lesions mimicking gastrointestinal stromal tumors

    PubMed Central

    Chen, Xue; Cao, Hailong; Wang, Sinan; Wang, Dan; Xu, Mengque; Piao, Meiyu; Wang, Bangmao

    2016-01-01

    Abstract Background: Dieulafoy lesion is a rare but serious cause of gastrointestinal hemorrhage. However, some cases can be occasionally found without bleeding during the endoscopic screening, and the management remains unclear. The aim of this article was to report the efficacy and safety of endoscopic submucosal dissection (ESD) for silent gastric Dieulafoy lesions, which presented as protrusion lesions mimicking gastrointestinal stromal tumors (GISTs). Methods: Data from the patients with gastric protrusion lesions who underwent ESD from September 2008 to April 2016 in General Hospital, Tianjin Medical University, China were recorded. Seven cases with pathological diagnosis of Dieulafoy lesion without bleeding were enrolled for further analysis. Results: A total of 7 patients (2 males and 5 females) with mean age of 57.7 ± 4.15 years were pathologically diagnosed as Dieulafoy lesion. Four of the lesions were located in gastric antrum, 2 in the fundus, and 1 in the body of stomach, respectively. The mean sizes of the Dieulafoy lesions under white light endoscopy and endoscopic ultrasonography (EUS) were 1.06 ± 0.28 and 0.84 ± 0.29 cm. The origins of these lesions were submucosa (6/7, 85.7%) and muscularis propria (1/7, 14.3%). Three of them appeared with mixed echo under EUS, 3 with hypoechogenicity, and 1 with hyperechogenicity. En bloc complete resection was achieved in all the lesions by ESD with average time of 76.00 ± 16.86 minutes, and no intraoperative bleeding happened. In addition, all patients were followed up for 1 to 53 months, and no recurrence or long-term complications was observed. Conclusion: Therefore, ESD can be an effective and safe treatment for silent gastric Dieulafoy lesions with clinical presentations of submucosal protrusion lesions mimicking GISTs. PMID:27603399

  13. GLP-2 receptors in human disease: high expression in gastrointestinal stromal tumors and Crohn's disease.

    PubMed

    Körner, Meike; Rehmann, Ruth; Reubi, Jean Claude

    2012-11-25

    Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

  14. The DREAM complex in anti-tumor activity of imatinib mesylate in gastrointestinal stromal tumors (GISTs)

    PubMed Central

    DeCaprio, James A.; Duensing, Anette

    2014-01-01

    Purpose of review Although most gastrointestinal stromal tumors (GISTs) respond well to treatment with the small molecule kinase inhibitor imatinib mesylate (Gleevec), the majority of patients achieve disease stabilization and complete remissions are rare. Furthermore, discontinuation of treatment in the presence of residual tumor mass almost inevitably leads to tumor progression. These observations suggest that a subset of tumor cells not only persists under imatinib treatment, but remains viable. The current article reviews the molecular basis for these findings and explores strategies to exploit them therapeutically. Recent findings Although imatinib can induce apoptosis in a subset of GIST cells, it can induce a reversible exit from the cell division cycle and entry into G0, a cell cycle state called quiescence, in the remaining cells. Mechanistically, this process involves the DREAM complex, a newly identified key regulator of quiescence. Interfering with DREAM complex formation either by siRNA-mediated knockdown or by pharmacological inhibition of the regulatory kinase DYRK1A was shown to enhance imatinib-induced GIST cell death. Summary Targeting the DREAM complex and imatinib-induced quiescence could provide opportunities for future therapeutic interventions toward more efficient imatinib responses. PMID:24840522

  15. A Case of a Gastrointestinal Stromal Tumor Diagnosed at the Postpartum Period

    PubMed Central

    Canda, Aras Emre; Karadeniz, Emre; Yavuzsen, Tugba; Sagol, Ozgul; Obuz, Funda; Canda, Mehmet Serefettin

    2016-01-01

    Introduction. We discuss a rare gastrointestinal stromal tumor (GIST) case detected at the 10th postpartum week and we want to pay attention to the challenges and improvements in the diagnosis, surgery, chemotherapy, and follow-up of this rare tumor accompanied with the review of the current literature. Case Presentation. A 32-year-old multiparous woman presented with abdominal swelling 10 weeks after her second vaginal birth. Abdominal examination revealed a mass starting from the pelvic level and extending to the right upper quadrant. Radiological examinations showed a solid, multiloculated, and hypervascular mass starting from the pelvis and extending to the transverse colon. En bloc mass with a 20 cm jejunal segment resection and a left pelvic side wall peritonectomy with omentectomy was performed. The pathologic examination revealed a high-risk GIST which originated from the jejunum and disseminated to the peritoneum. The patient has been given imatinib 400 mg/day since then. She did not reveal any progression during the 15-month follow-up postoperatively. Conclusion. GIST tumors are rare and there is not sufficient information in the literature regarding its management. In this patient having high risk GIST and GIST sarcomatosis we successfully treated the patient by surgery and adjuvant imatinib chemotherapy. PMID:27957364

  16. The roles of serum CXCL16 in circulating Tregs and gastrointestinal stromal tumor cells

    PubMed Central

    Xing, Ya-Nan; Zhang, Jun-Yan; Xu, Hui-Mian

    2016-01-01

    Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the digestive system. Abnormal expression of CXCL16 and its sole receptor, CXCR6, has been demonstrated in many cancers. However, no studies have shown the relationship between CXCL16 or CXCR6 expression and GIST. In this study, we detected CXCL16 and CXCR6 expression in GIST patient samples by using immunohistochemistry analysis and Western blot analysis. Serum CXCL16 level was determined by using enzyme-linked immunosorbent assay. Circulating Tregs were isolated by using flow cytometry. MTT assay, cell cycle assay, and transwell assay were used to test the effects of recombinant CXCL16 on Tregs and GIST cells in vitro. The levels of CXCL16 and CXCR6 protein were higher in cancer tissues than in normal tissues. Serum CXCL16 level and circulating Tregs were higher in GIST patients than that in the healthy volunteers. CXCL16, CXCR6, serum CXCL16, and circulating Tregs were significantly associated with a decreased survival time of patients. Relative to control cells, high concentration recombinant CXCL16 treated Tregs and GIST cells exhibited lower proliferation and mobility rates as assessed by MTT assay and transwell assay, respectively. Taken together, CXCL16 was observed to mediate the inhibitory effects in Tregs and GIST cells, and these involved suppression of the MEK/ERK signaling pathway. PMID:27418838

  17. Primary gastrointestinal stromal tumour of the ileum pre-operatively diagnosed as an abdominal abscess

    PubMed Central

    Rubini, Patrizia; Tartamella, Francesco

    2016-01-01

    The present case report described the acute presentation, diagnosis and management of a primary gastrointestinal stromal tumour (GIST) of the ileum. A male patient (age, 51 years) was admitted to Maggiore Hospital (Parma, Italy) due to presenting with fever, dysuria and lower abdominal pain. Ultrasonography and computed tomography showed a 7,5×5,5-cm pelvic mass containing air and purulent fluid indicative of an intraperitoneal abscess. The patient was subjected to diagnostic laparoscopy, which revealed a huge, soft cystic mass arising from the small bowel. The procedure was then converted to an open exploration through a midline incision. Ileal resection including a Meckel's diverticulum was performed. Macroscopic examination revealed that the cystic mass was filled with a large amount of pus, probably due to communication between the tumour mass and the small bowel lumen. In fact, the surgical specimen showed enteric leakage from the ileal mucosal ulcer into the tumour mass. Histopathology and immunohistochemistry of the abscess wall identified a spindle-cell mesenchymal-type, c-KIT-positive neoplasm. The post-operative course was uneventful and adjuvant imatinib mesylate was administered for 1 year. Follow-up by computed tomography demonstrated no tumour recurrence at 72 months after surgery. PMID:27900093

  18. Integrative Genomic Characterization and a Genomic Staging System for Gastrointestinal Stromal Tumors

    PubMed Central

    Ylipää, Antti; Hunt, Kelly K.; Yang, Jilong; Lazar, Alexander J. F.; Torres, Keila E.; Lev, Dina Chelouche; Nykter, Matti; Pollock, Raphael E.; Trent, Jonathan; Zhang, Wei

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) were historically grouped with leiomyosarcomas (LMSs) based on their morphological similarities, but recently they have been unequivocally established as a distinct type of sarcoma based on the molecular features and response to imatinib treatment. To gain further insight into the genomic differences between GISTs and LMSs, we mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated them with gene expression profiles. Our studies revealed distinct patterns of CNAs between GISTs and LMSs. Losses in chromosomes 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < 0.001), whereas losses in chromosomes 10 and 16 as well as gains in 1q, 14q, and 15q (P < 0.001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, we found several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into four groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were differently expressed in the four groups and the patients had increasingly worse prognosis as the extent of genomic alterations increased. These findings lead us to propose a new tumor-progression genetic staging system termed Genomic Instability Stage (GIS) to complement the current prognostic predictive system based on tumor size, mitotic index (MI), and KIT mutation. PMID:20818650

  19. ZNF-Mediated Resistance to Imatinib Mesylate in Gastrointestinal Stromal Tumor

    PubMed Central

    Zhou, Yan; von Mehren, Margaret; Godwin, Andrew K.

    2013-01-01

    Although imatinib mesylate (IM) has transformed the treatment of gastrointestinal stromal tumors (GIST), many patients experience primary/secondary drug resistance. In a previous study, we identified a gene signature, consisting mainly of Kruppel-associated box (KRAB) domain containing zinc finger (ZNF) transcriptional repressors that predict short-term response to IM. To determine if these genes have functional significance, a siRNA library targeting these genes was constructed and applied to GIST cells in vitro. These screens identified seventeen “IM sensitizing genes” in GIST cells (sensitization index (SI) <0.85 ratio of drug/vehicle) with a false discovery rate (FDR) <15%, including twelve ZNF genes, the majority of which are located within the HSA19p12–13.1 locus. These genes were shown to be highly specific to IM and another tyrosine kinase inhibitor (TKI), sunitinib, in GIST cells. In order to determine mechanistically how these ZNFs might be modulating response to IM, RNAi approaches were used to individually silence genes within the predictive signature in GIST cells and expression profiling was performed. Knockdown of the 14 IM-sensitizing genes (10 ZNFs) universally led to downregulation of six genes, including TGFb3, periostin, and NEDD9. These studies implicate a role of KRAB-ZNFs in modulating response to TKIs in GIST. PMID:23372733

  20. KIT and PDGFRA mutations and PDGFRA immunostaining in gastrointestinal stromal tumors.

    PubMed

    Barreca, Antonella; Fornari, Alessandro; Bonello, Lisa; Tondat, Fabrizio; Chiusa, Luigi; Lista, Patrizia; Pich, Achille

    2011-01-01

    In the present study, we investigated the association of PDGFRA and KIT mutations as well as PDGFRA immunohistochemical expression with clinicopathologic features and prognosis in a series of gastrointestinal stromal tumors (GISTs). Tumor DNA from 40 GISTs was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17, and in PDGFRA exons 12 and 18. Tissue sections were stained with polyclonal anti-PDGFRA antibody. KIT mutations occurred in 26 cases. There were 13 deletions, 6 substitutions, 3 deletion-substitutions, 3 duplications and 1 insertion. Tumors with KIT deletions/insertion were large with a high mitotic index (MI), and were associated with a high rate of symptoms at diagnosis, invasion into adjacent organs, distant metastasis, relapse and a short disease-free survival (DFS). PDGFRA mutations occurred in 6 gastric GISTs. There were 4 deletions and 2 substitutions. Tumors with PDGFRA mutations were small, with a low MI and Ki67 score, and were associated with a very low rate of symptoms at diagnosis, invasion into adjacent organs and distant metastasis. PDGFRA immunopositivity was found in 23 cases: a peculiar 'dotlike' staining was found in 5 out of 6 PDGFRA mutated cases. Patients with positive PDGFRA immunostaining had a longer DFS than those with negative staining. Our data confirm that the type of KIT mutation is associated with various clinicopathologic features of GISTs, and indicate that PDGFRA mutations are associated with rather indolent tumors. PDGFRA immunopositivity reflects PDGFRA mutational status and is associated with a favorable outcome.

  1. Kinase genotype analysis of gastric gastrointestinal stromal tumor cytology samples using targeted next-generation sequencing.

    PubMed

    Gleeson, Ferga C; Kipp, Benjamin R; Kerr, Sarah E; Voss, Jesse S; Graham, Rondell P; Campion, Michael B; Minot, Douglas M; Tu, Zheng J; Klee, Eric W; Lazaridis, Konstantinos N; Henry, Michael R; Levy, Michael J

    2015-01-01

    Gastric gastrointestinal stromal tumors (GISTs) usually contain the mast/stem cell growth factor receptor Kit gene (KIT) or platelet-derived growth factor receptor A (PDGFRA) mutations that can be targeted by, or mediate resistance to, imatinib. Diagnostic material often is obtained by endoscopic ultrasound-guided fine-needle aspiration, which often is unsuitable for molecular analysis. We investigated whether targeted next-generation sequencing (NGS) can be used in multiplex genotype analysis of cytology samples collected by endoscopic ultrasound-guided fine-needle aspiration. We used the Ion AmpliSeq V2 Cancer Hotspot NGS Panel (Life Technologies, Carlsbad, CA) to identify mutations in more than 2800 exons from 50 cancer-associated genes in GIST samples from 20 patients. We identified KIT mutations in 58% of samples (91% in exon 11 and 9% in exon 17) and PDGFRA mutations in 26% (60% in exon 18 and 40% in exon 12); 16% of samples had no mutations in KIT or PDGFRA. No pathogenic alterations were found in PIK3CA, BRAF, KRAS, NRAS, or FGFR3. We predicted that 32% of patients would have primary resistance to imatinib, based on mutations in exon 17 of KIT, exon 18 of PDGFRA (D842V), or no mutation in either gene. Targeted NGS of cytology samples from GISTs is feasible and provides clinically relevant data about kinase genotypes that can help guide individualized therapy.

  2. Pharmacological inhibition of KIT activates MET signaling in gastrointestinal stromal tumors

    PubMed Central

    Cohen, Noah A.; Zeng, Shan; Seifert, Adrian M.; Kim, Teresa S.; Sorenson, Eric C.; Greer, Jonathan B.; Beckman, Michael J.; Santamaria-Barria, Juan A.; Crawley, Megan H.; Green, Benjamin L.; Rossi, Ferdinand; Besmer, Peter; Antonescu, Cristina R.; DeMatteo, Ronald P.

    2015-01-01

    Gastrointestinal stromal tumors (GIST) are the most common adult sarcomas and the oncogenic driver is usually a KIT or PDGFRA mutation. While GIST are often initially sensitive to imatinib or other tyrosine kinase inhibitors, resistance generally develops necessitating backup strategies for therapy. In this study, we determined that a subset of human GIST specimens that acquired imatinib resistance acquired expression of activated forms of the MET oncogene. MET activation also developed after imatinib therapy in a mouse model of GIST (KitV558del/+ mice), where it was associated with increased tumor hypoxia. MET activation also occurred in imatinib-sensitive human GIST cell lines after imatinib treatment in vitro. MET inhibition by crizotinib or RNA interference was cytotoxic to an imatinib-resistant human GIST cell population. Moreover, combining crizotinib and imatinib was more effective than imatinib alone in imatinib-sensitive GIST models. Lastly, cabozantinib, a dual MET and KIT small molecule inhibitor, was markedly more effective than imatinib in multiple preclinical models of imatinib-sensitive and imatinib-resistant GIST. Collectively, our findings showed that activation of compensatory MET signaling by KIT inhibition may contribute to tumor resistance. Furthermore, our work offered a preclinical proof of concept for MET inhibition by cabozantinib as an effective strategy for GIST treatment. PMID:25836719

  3. Primary omental gastrointestinal stromal tumour (GIST) presenting with a large abdominal mass and spontaneous haemoperitoneum.

    PubMed

    Seow-En, Isaac; Seow-Choen, Francis; Lim, Tony Kiat Hon; Leow, Wei Qiang

    2014-11-03

    A 60-year-old Indonesian woman presented with a 9-day history of increasing abdominal distension, pain and tiredness. Physical examination revealed significant pallor with a palpable mass in the abdomen. CT of the abdomen reported a 22 cm complex mass in the peritoneal cavity with free intra-abdominal fluid. Laboratory results showed anaemia with a raised serum CA 125 level. At laparotomy a large haemorrhagic tumour with blood filled cystic cavities was found attached to both greater omentum and the transverse mesocolon with 2.2 L of blood in the peritoneal cavity. There was no invasion of any part of the stomach or intestines and there were no metastases seen. Histopathology of the resected specimen was consistent with that of a gastrointestinal stromal tumour arising from the omentum. Immunohistochemical studies revealed the tumour to be strongly positive for discovered on GIST-1 (DOG1) but negative for both CD117 and CD34. Platelet-derived growth factor receptor α (PDGFRA) exon 18 mutation D842V was detected.

  4. Drug Repurposing Identifies a Synergistic Combination Therapy with Imatinib Mesylate for Gastrointestinal Stromal Tumor

    PubMed Central

    Pessetto, Ziyan Y.; Ma, Yan; Hirst, Jeff J.; von Mehren, Margaret; Weir, Scott J.; Godwin, Andrew K.

    2014-01-01

    Gastrointestinal Stromal Tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor, imatinib mesylate (IM) radically improved the clinical response of patients with GIST; however, its effects are often short-lived, with GISTs demonstrating a median time to progression of approximately two years. Although many investigational drugs, approved first for other cancers, have been subsequently evaluated for the management of GIST, few have greatly impacted the overall survival of patients with advanced disease. We employed a novel, focused, drug repurposing effort for GIST including IM-resistant GIST evaluating a large library of FDA-approved drugs regardless of current indication. As a result of the drug repurposing screen, we identified eight FDA-approved drugs including fludarabine phosphate (F-AMP) that showed synergy with and/or overcame resistance to IM. F-AMP induces DNA damage, annexin V and caspase 3/7 activities as the cytotoxic effects on GIST cells, including IM-resistant GIST cells. F-AMP and IM combination treatment showed greater inhibition of GIST cell proliferation when compared to IM alone and F-AMP alone. Successful in vivo experiments confirmed the combination of IM with F-AMP enhanced the antitumor effects compared to IM alone. Our results identified F-AMP as a promising, repurposed drug therapy for the treatment of GISTs, with potential to be administered in combination with IM or for treatment of IM-refractory tumors. PMID:25122069

  5. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.

    PubMed

    Killian, J Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Smith, William I; Jahromi, Mona S; Xekouki, Paraskevi; Szarek, Eva; Walker, Robert L; Lasota, Jerzy; Raffeld, Mark; Klotzle, Brandy; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J; O'Sullivan, Maureen J; Bibikova, Marina; Pacak, Karel; Stratakis, Constantine; Janeway, Katherine A; Schiffman, Joshua D; Fan, Jian-Bing; Helman, Lee; Meltzer, Paul S

    2013-06-01

    Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.

  6. Beyond Standard Therapy: Drugs Under Investigation for The Treatment of Gastrointestinal Stromal Tumor

    PubMed Central

    Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K

    2015-01-01

    Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival. PMID:26098203

  7. Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis.

    PubMed

    Martin-Broto, J; Martinez-Marín, V; Serrano, C; Hindi, N; López-Guerrero, J A; Ramos-Asensio, R; Vallejo-Benítez, A; Marcilla-Plaza, D; González-Cámpora, R

    2016-12-09

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.

  8. Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor

    PubMed Central

    Rossi, Ferdinand; Ehlers, Imke; Agosti, Valter; Socci, Nicholas D.; Viale, Agnes; Sommer, Gunhild; Yozgat, Yasemin; Manova, Katia; Antonescu, Cristina R.; Besmer, Peter

    2006-01-01

    Kit receptor-activating mutations are critical in the pathogenesis of gastrointestinal stromal tumors (GIST). We investigated mechanisms of oncogenic Kit signaling and the consequences of therapeutic intervention in a mouse model of human GIST. Treatment of GIST mice with imatinib decreased cell proliferation and increased apoptosis in the tumor. Analysis of tumor tissue from imatinib-treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit signaling critically contributes to the translational response in GIST. Treatment with RAD001 (everolimus), an mTOR inhibitor, diminished the translational response and cell proliferation in tumor lesions, pointing to mTOR inhibition as a therapeutic approach for imatinib-resistant GIST. Analysis of RNA expression profiles in GIST lesions with and without imatinib treatment showed changes in expression of IFN-inducible genes and cell cycle regulators. These results convincingly show that KitV558Δ/+ mice represent a unique faithful mouse model of human familial GIST, and they demonstrate the utility of these mice for preclinical investigations and to elucidate oncogenic signaling mechanisms by using genetic approaches and targeted pharmacological intervention. PMID:16908864

  9. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the stomach: report of three cases.

    PubMed

    Oh, Ji Seon; Lee, Jae-Lyun; Kim, Mi-Jung; Ryu, Min-Hee; Chang, Heung Moon; Kim, Tae Won; Jang, Se Jin; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kang, Yoon-Koo

    2006-01-01

    Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

  10. Genomic and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumors

    PubMed Central

    Takahashi, Tsuyoshi; Elzawahry, Asmaa; Mimaki, Sachiyo; Furukawa, Eisaku; Nakatsuka, Rie; Nakamura, Hiromi; Nishigaki, Takahiko; Serada, Satoshi; Naka, Tetsuji; Hirota, Seiichi; Shibata, Tatsuhiro; Tsuchihara, Katsuya

    2017-01-01

    Gastrointestinal stromal tumors represent the most common mesenchymal tumor of the digestive tract, driven by gain‐of‐function mutations in KIT. Despite its proven benefits, half of the patients treated with imatinib show disease progression within 2 years due to secondary resistance mutations in KIT. It remains unclear how the genomic and transcriptomic features change during the acquisition of imatinib resistance. Here, we performed exome sequencing and microarray transcription analysis for four imatinib‐resistant cell lines and one cell line briefly exposed to imatinib. We also performed exome sequencing of clinical tumor samples. The cell line briefly exposed to imatinib exhibited few single‐nucleotide variants and copy‐number alterations, but showed marked upregulation of genes related to detoxification and downregulation of genes involved in cell cycle progression. Meanwhile, resistant cell lines harbored numerous genomic changes: amplified genes related to detoxification and deleted genes with cyclin‐dependent kinase activity. Some variants in the resistant samples were traced back to the drug‐sensitive samples, indicating the presence of ancestral subpopulations. The subpopulations carried variants associated with cell death. Pre‐existing cancer cells with genetic alterations promoting apoptosis resistance may serve as a basis whereby cancer cells with critical mutations, such as secondary KIT mutations, can establish full imatinib resistance. © 2017 The Authors Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc. PMID:27997714

  11. Duration of adjuvant treatment following radical resection of metastases from gastrointestinal stromal tumours

    PubMed Central

    NANNINI, MARGHERITA; PANTALEO, MARIA ABBONDANZA; MALEDDU, ALESSANDRA; SAPONARA, MARISTELLA; MANDRIOLI, ANNA; LOLLI, CRISTIAN; PALLOTTI, MARIA CATERINA; GATTO, LIDIA; SANTINI, DONATELLA; PATERINI, PAOLA; DI SCIOSCIO, VALERIO; CATENA, FAUSTO; FUSAROLI, PIETRO; PINNA, ANTONIO DANIELE; DEI TOS, ANGELO PAOLO; BIASCO, GUIDO

    2011-01-01

    Large-scale studies have demonstrated that continuative treatment in advanced and adjuvant settings results in a gain-of-survival. However, the discontinuation, and the duration of treatment in disease-free patients who have undergone radical surgical resection of metastases from gastrointestinal stromal tumours (GISTs) have yet to be evaluated. We retrospectively reviewed 40 patients with advanced and recurrent GIST, included in our GIST database, focusing on patients (5 males and 2 females; median age 56 years) who continued medical treatment following radical surgical resection of metastatic lesions. Seven out of 40 patients underwent surgery and continued medical treatment following radical surgical resection of metastatic lesions. The duration of adjuvant therapy was 3, 12, 16, 24, 35, 37 and 52 months, respectively, with a median of 26 months. No patients discontinued therapy and all were disease-free at the final CT-scan evaluation. Considering that the discontinuation of imatinib in responding patients with advanced GIST (even in complete remission) results in a rapid high risk of progression, and a short adjuvant therapy results in a shorter disease-free and overall survival in high-risk GIST patients, it is also likely that treatment should not be discontinued in this setting. However, large-scale studies are required to better assess the optimal duration of treatment, particularly after 5 years, by focusing on the identification of predictive factors for the selection of patients who may benefit from a prolonged or lifelong imatinib treatment. PMID:22740975

  12. Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors

    PubMed Central

    Lee, Na Keum; Lee, Jung Hwa; Kim, Won Kyu; Yun, Seongju; Youn, Young Hoon; Park, Chan Hyuk; Choi, Yun Young; Kim, Hogeun; Lee, Sang Kil

    2016-01-01

    HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells. Using a gene expression microarray and lists of HOTAIR-associated candidate genes, we suggested that protocadherin 10 (PCDH10) is a key molecule. PCDH10 expression was significantly decreased in GIST-T1 and GIST882 cells, possibly as a consequence of hypermethylation. We observed that HOTAIR induced PCDH10 methylation in a SUZ12-dependent manner. In this study, we found that the malignant character of GISTs was initiated and amplified by PCDH10 in a process regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be useful markers of disease progression and therapeutic targets. PMID:27659532

  13. Safety of Regular-Dose Imatinib Therapy in Patients with Gastrointestinal Stromal Tumors Undergoing Dialysis.

    PubMed

    Niikura, Ryota; Serizawa, Takako; Yamada, Atsuo; Yoshida, Shuntaro; Tanaka, Mariko; Hirata, Yoshihiro; Koike, Kazuhiko

    2016-01-01

    The number of cancer patients undergoing dialysis has been increasing, and the number of these patients on chemotherapy is also increasing. Imatinib is an effective and safe therapy for KIT-positive gastrointestinal stromal tumors (GIST), but the efficacy and safety of imatinib in dialysis patients remain unclear. Because clinical trials have not been conducted in this population, more investigations are required. We report on a 75-year-old Japanese man undergoing dialysis who presented with massive tarry stool from a duodenal GIST. The duodenal GIST was 14 cm in diameter with multiple liver and bone metastases. The patient underwent an urgent pancreaticoduodenectomy to achieve hemostasis. After surgery, he was administered imatinib 400 mg/day. No severe adverse event including myelosuppression, congestive heart failure, liver functional impairment, intestinal pneumonia, or Steven-Johnson syndrome occurred, and the liver metastasis remained stable for 4 months. During chemotherapy, hemodialysis continued three times per week without adverse events. We suggest that regular-dose imatinib is an effective and safe treatment in patients with GIST undergoing dialysis. In addition, we present a literature review of the effectiveness and safety of imatinib treatment in dialysis patients.

  14. NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors

    PubMed Central

    Demetri, George D.; von Mehren, Margaret; Antonescu, Cristina R.; DeMatteo, Ronald P.; Ganjoo, Kristen N.; Maki, Robert G.; Pisters, Peter W.T.; Raut, Chandrajit P.; Riedel, Richard F.; Schuetze, Scott; Sundar, Hema M.; Trent, Jonathan C.; Wayne, Jeffrey D.

    2014-01-01

    The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting. PMID:20457867

  15. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

    PubMed Central

    2010-01-01

    Background Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs. Methods Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples. Results Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA. Conclusions The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these

  16. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer

    PubMed Central

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-01-01

    Abstract The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer. From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed. Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474). The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer. PMID:27828865

  17. A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors

    PubMed Central

    Nojima, Masanori; Kai, Masahiro; Yamamoto, Eiichiro; Maruyama, Reo; Nobuoka, Takayuki; Nishida, Toshirou; Kanda, Tatsuo; Taguchi, Takahiro; Hasegawa, Tadashi; Tokino, Takashi; Hirata, Koichi; Suzuki, Hiromu; Shinomura, Yasuhisa

    2015-01-01

    Background Dysregulation of microRNA (miRNA) has been implicated in gastrointestinal stromal tumors (GISTs) but the mechanism is not fully understood. In this study, we aimed to explore the involvement of epigenetic alteration of miRNA genes in GISTs. Methods GIST-T1 cells were treated with 5-aza-2’-deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (PBA), after which miRNA expression profiles were analyzed using TaqMan miRNA arrays. DNA methylation was then analyzed using bisulfite pyrosequencing. The functions of miRNAs were examined using MTT assays, wound-healing assays, Boyden chamber assays and Matrigel invasion assays. Gene expression microarrays were analyzed to assess effect of ectopic miRNA expression in GIST-T1 cells. Results Of the 754 miRNAs analyzed, 61 were significantly upregulated in GIST-T1 cells treated with 5-aza-dC plus PBA. Among those, 21 miRNA genes were associated with an upstream CpG island (CGI), and the CGIs of miR-34a and miR-335 were frequently methylated in GIST-T1 cells and primary GIST specimens. Transfection of miR-34a or miR-335 mimic molecules into GIST-T1 cells suppressed cell proliferation, and miR-34a also inhibited migration and invasion by GIST-T1 cells. Moreover, miR-34a downregulated a number of predicted target genes, including PDGFRA. RNA interference-mediated knockdown of PDGFRA in GIST-T1 cells suppressed cell proliferation, suggesting the tumor suppressive effect of miR-34a is mediated, at least in part, through targeting PDGFRA. Conclusions Our results suggest that miR-34a and miR-335 are candidate tumor suppressive miRNAs in GISTs, and that they are frequent targets of epigenetic silencing in GISTs. PMID:26214687

  18. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors

    PubMed Central

    Tarn, Chi; Rink, Lori; Merkel, Erin; Flieder, Douglas; Pathak, Harsh; Koumbi, Daphne; Testa, Joseph R.; Eisenberg, Burton; von Mehren, Margaret; Godwin, Andrew K.

    2008-01-01

    A subset of gastrointestinal stromal tumors (GISTs) lack gain-of-function mutations in c-KIT and PDGFRα. These so-called wild-type (WT) GISTs tend to be less responsive to imatinib-based therapies and have a poor prognosis. We identified amplification of IGF1R in a SNP analysis of GIST and thus studied its potential as a therapeutic target in WT and mutant GIST. Expression of IGF1R and downstream effectors in clinical GIST samples was examined by using immunoblots and immunohistochemistry. The roles of IGF1R signaling in GIST and viability were analyzed by using NVP-AEW541, an inhibitor of IGF1R, alone and in combination with imatinib, or via siRNA silencing of IGF1R. IGF1R was strongly overexpressed, and IGF1R amplification was detected at a significantly higher frequency in WT GISTs, including a pediatric WT GIST, compared with mutant GISTs (P = 0.0173 and P = 0.0163, respectively). Inhibition of IGF1R activity in vitro with NVP-AEW541 or down-regulation of expression with siIGF1R led to cytotoxicity and induced apoptosis in GIST cell lines via AKT and MAPK signaling. Combination of NVP-AEW541 and imatinib in GIST cell lines induced a strong cytotoxicity response. Our results reveal that IGF1R is amplified and the protein is overexpressed in WT and pediatric GISTs. We also demonstrate that the aberrant expression of IGF1R may be associated with oncogenesis in WT GISTs and suggest an alternative and/or complementary therapeutic regimen in the clinical management of all GISTs, especially in a subset of tumors that respond less favorably to imatinib-based therapy. PMID:18550829

  19. Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.

    PubMed

    Saponara, Maristella; Pantaleo, Maria Abbondanza; Nannini, Margherita; Biasco, Guido

    2012-12-01

    The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained that oral drug administration entails new and relevant management problems. Multiple studies have demonstrated the efficacy of imatinib in GISTs associated with a good toxicity profile. However, the efficacy of imatinib, according to its mechanism of action and pharmacokinetics, is closely related to daily assumption. No interruption or "jerky" assumption is permitted in order to avoid efficacy loss. Thus, the issue of treatment adherence is crucial for a successful strategy and should not be overlooked. We think that dealing with the problem means assessing a wide spectrum of not only clinical and general but also psychological and individual aspects. Furthermore, both patient and family should play an active role in the "cure process" and physicians should reduce the distance separating them from their patients due to home-based target therapy, promoting communication and consolidation of a trust-based physician-patient relationship. Several advantages have been introduced by oral target therapies in oncology. However, chronic drug administration, even if generally well tolerated, when prolonged for an undetermined time could heavily impact on patients' quality of life. This could induce non-prescribed drug suspension, with negative impact on disease control. More studies would be necessary in order to detect real patients' adherence, to correlate drug assumption with clinical outcome and to optimize imatinib treatment strategy.

  20. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer.

    PubMed

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-11-01

    The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer.From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed.Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474).The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer.

  1. Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib

    PubMed Central

    Moryoussef, Frédérick; Dhooge, Marion; Volet, Julien; Barbe, Coralie; Brezault, Catherine; Hoeffel, Christine; Coriat, Romain; Bouché, Olivier

    2015-01-01

    Background Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia. Methods Thirty-one patients with advanced (n = 16) or high-risk resected (n = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration. Results Twelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre-treatment sarcopenia was not associated with grades 3–4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p < 0.01) after 3 months of treatment. Grades 1–2 anaemia and grades 1–2 fatigue were more frequent for sarcopenic than non-sarcopenic patients (83% vs. 26%, P < 0.01 and 42% vs. 5%, P = 0.02, respectively). Conclusions Sarcopenia is reversible in some GIST patients treated with imatinib. Pre-imatinib sarcopenia is predictive of non-severe toxicities, particularly anaemia and fatigue. PMID:26673372

  2. Severe Imatinib-Associated Skin Rash in Gastrointestinal Stromal Tumor Patients: Management and Clinical Implications

    PubMed Central

    Park, Sook Ryun; Ryu, Min-Hee; Ryoo, Baek-Yeol; Beck, Mo Youl; Lee, In Soon; Choi, Mi Jung; Lee, Mi Woo; Kang, Yoon-Koo

    2016-01-01

    Purpose This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. Materials and Methods A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. Results Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). Conclusion By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions. PMID:26323636

  3. Transcriptomic reappraisal identifies MGLL overexpression as an unfavorable prognosticator in primary gastrointestinal stromal tumors

    PubMed Central

    Liu, Ting-Ting; Chen, Ko-Chin; Chen, Yen-Yang; Fang, Fu-Min; Li, Shau-Hsuan; Chen, Tzu-Ju; Yu, Shih-Chen; Lan, Jui; Huang, Hsuan-Ying

    2016-01-01

    The role of deregulated cellular metabolism, particularly lipid metabolism, in gastrointestinal stromal tumors (GISTs) remains unclear. Through data mining of published transcriptomes, we examined lipid metabolism-regulating drivers differentially upregulated in high-risk cases and identified monoglyceride lipase (MGLL) as the top-ranking candidate involved in GIST progression. MGLL expression status was examined in three GIST cell lines and two independent sets of primary localized GISTs. MGLL mRNA abundance and immunoexpression was determined in 70 cases through the QuantiGene assay and H-scoring on whole sections, respectively. H-scoring was extended to another cohort for evaluating MGLL immunoexpression on tissue microarrays, yielding 350 informative cases, with KIT/PDGFRA mutation genotypes noted in 213 of them. Both imatinib-sensitive (GIST882) and -resistant (GIST48 and GIST430) cell lines exhibited increased MGLL expression. MGLL mRNA levels significantly increased from adjacent normal tissue to the non-high-risk group (p = 0.030) and from the non-high-risk group to high-risk GISTs (p = 0.012), and were associated with immunoexpression levels (p < 0.001, r = 0.536). MGLL overexpression was associated with the nongastric location (p = 0.022) and increased size (p = 0.017), and was strongly related to mitosis and risk levels defined by NIH and NCCN criteria (all p ≤ 0.001). Univariately, MGLL overexpression was strongly predictive of poorer disease-free and overall survival (both p < 0.001), which remained prognostically independent for both endpoints, along with higher risk levels. Conclusively, MGLL is a lipid metabolic enzyme causatively implicated in GIST progression given its association with unfavorable clincopathological factors and independent negative prognostic effects. PMID:27366945

  4. Detection of Treatment-Induced Changes in Signaling Pathways in Gastrointestinal Stromal Tumors using Transcriptomic Data

    PubMed Central

    Ochs, Michael F.; Rink, Lori; Tarn, Chi; Mburu, Sarah; Taguchi, Takahiro; Eisenberg, Burton; Godwin, Andrew K.

    2009-01-01

    Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins, however off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally feasible during treatment, there is a need for more powerful methods to determine if therapeutics inhibit their targets and when off-target effects occur. We have used the Bayesian Decomposition algorithm and data on transcriptional regulation to create a novel methodology, DESIDE (Differential Expression for SIgnaling DEtermination), for inferring signaling activity from microarray measurements. We applied DESIDE to deduce signaling activity in gastrointestinal stromal tumor cell lines treated with the targeted therapeutic imatinib mesylate (Gleevec). We detected the expected reduced activity in the KIT pathway, as well as unexpected changes in the P53 pathway. Pursuing these findings, we have determined that imatinib-induced DNA damage is responsible for the increased activity of P53, identifying a novel off-target activity for this drug. We then used DESIDE on data from resected, post-imatinib treatment tumor samples and identified a pattern in these tumors similar to that at late time points in the cell lines, and this pattern correlated with initial clinical response. The pattern showed increased activity of ELK1 and STAT3 transcription factors, which are associated with the growth of side population cells. DESIDE infers the global reprogramming of signaling networks during treatment, permitting treatment modification that leverages ongoing drug development efforts, which is crucial for personalized medicine. PMID:19903850

  5. Concurrent gastrointestinal stromal tumor and digestive tract carcinoma: a single institution experience in China

    PubMed Central

    Zhang, Peng; Deng, Rui; Xia, Zefeng; Shuai, Xiaoming; Chang, Weilong; Gao, Jinbo; Wang, Guobin; Tao, Kaixiong

    2015-01-01

    The aim of this study was to review the clinicopathological characteristics and survival outcomes of patients with concurrent gastrointestinal stromal tumor (GIST) and digestive tract carcinoma. Among 585 patients diagnosed with GIST from January 2005 to July 2014, 32 (5.5%) had synchronous digestive tract carcinoma, including 19 (59.4%) men and 13 (40.6%) women. The median age was 64 years (range, 43-84). GIST was located in the stomach (n=24), small intestine (n=6), duodenum (n=1) and retroperitoneum (n=1). GISTs were intra- or postoperatively discovered (n=28) or preoperatively identified (n=4). The tumor size was less than 10 mm (microGIST) in 23 (71.9%) GIST patients. The preoperatively identified GIST subgroup showed a significantly larger tumor size, more mitotic figures and a higher risk grade than the intra- or postoperatively identified GIST subgroup. Concurrent digestive tract carcinomas were most frequently located in the stomach (24 cases, 75%). The other involved sites were the esophagus (n=5), duodenum (n=2) and colon (n=1). With a median follow-up of 32 months (range, 9-80), 24 patients were alive without evidence of disease, 6 patients had died of carcinoma progression, 1 patient had died from an accident, and 1 patient experienced GIST metastasis to the liver. In summary, we discovered that 5.5% of GIST patients also developed a concurrent digestive tract carcinoma in a series of 585 GIST cases. The majority of GISTs are incidentally identified microGISTs. The concurrent carcinoma seems to have a greater unfavorable effect on prognosis than the GIST. However, for a GIST that is identified preoperatively with a high risk of progression, adjuvant therapy is warranted. PMID:26885079

  6. Histopathological Features of Gastrointestinal Stromal Tumors and the Contribution of DOG1 Expression to the Diagnosis

    PubMed Central

    Güler, Beril; Özyılmaz, Filiz; Tokuç, Burcu; Can, Nuray; Taştekin, Ebru

    2015-01-01

    Background: Gastrointestinal stromal tumors (GIST) have KIT or platelet-derived growth factor receptor α (PDGFRα) mutations affecting receptor tyrosine kinase activity and do not benefit from classic treatment regimens. Aims: The aim of this study was to review the algorithm that may be followed for the diagnosis and differential diagnosis in GISTs by investigating the histomorphological parameters and expression characteristics of classical immunohistochemical antibodies used in routine tests in addition to DOG1 expression. Study Design: Diagnostic accuracy study. Methods: We reevaluated the histological and immunohistochemical parameters of 37 GISTs. The standard immunohistochemical diagnosis and differential diagnosis panel antibodies (CD117, PDGFRα, CD34, vimentin, desmin, SMA, S-100, and Ki67) were studied on the tumor sections. We also used the popular marker DOG1 antibody with accepted sensitivity for GISTs in recent years and the PDGFRα immune marker for which the benefit in routine practice is discussed. Results: Classification according to progressive disease risk groups of the 37 cases revealed that 54% were in the high risk, 19% in the moderate risk, 16% in the low risk, 8% in the very low risk and 8% in the no risk group. Cytological atypia, necrosis, mucosal invasion and the Ki67 index were found to be related to the progressive disease risk groups of the tumors (p<0.05). Positive immunoreaction was observed with CD117 and PDGFRα in all GISTs in the study (100%). Positivity with the DOG1 antibody was found in 33 (89%) cases. CD34 was positive in 62% (23) of the cases. Conclusion: The CD117 antibody still plays a key role in GIST diagnosis. However, the use of DOG1 and PDGFRα antibodies combined with CD117 as sensitive markers can be beneficial. PMID:26740899

  7. Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    PubMed

    Obata, Y; Horikawa, K; Takahashi, T; Akieda, Y; Tsujimoto, M; Fletcher, J A; Esumi, H; Nishida, T; Abe, R

    2017-02-13

    Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM). In imatinib-resistant GIST with a secondary Kit mutation, Kit localizes predominantly on the Golgi apparatus. Both imatinib-sensitive and imatinib-resistant Kit (Kit(mut)) become fully auto-phosphorylated only on the Golgi and only if in a complex-glycosylated form. Kit(mut) accumulates on the Golgi during the early secretory pathway, but not after endocytosis. The aberrant kinase activity of Kit(mut) prevents its export from the Golgi to the PM. Furthermore, Kit(mut) on the Golgi signals and activates the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway, signal transducer and activator of transcription 5 (STAT5), and the Mek-Erk pathway. Blocking the biosynthetic transport of Kit(mut) to the Golgi from the endoplasmic reticulum inhibits oncogenic signaling. PM localization of Kit(mut) is not required for its signaling. Activation of Src-family tyrosine kinases on the Golgi is essential for oncogenic Kit signaling. These results suggest that the Golgi apparatus serves as a platform for oncogenic Kit signaling. Our study demonstrates that Kit(mut)'s pathogenicity is related to its mis-localization, and may offer a new strategy for treating imatinib-resistant GISTs.Oncogene advance online publication, 13 February 2017; doi:10.1038/onc.2016.519.

  8. Dysregulated expression of Snail and E-cadherin correlates with gastrointestinal stromal tumor metastasis.

    PubMed

    Liu, Sheng; Liao, Guoqing; Ding, Jie; Ye, Ke; Zhang, Yi; Zeng, Liang; Chen, Senlin

    2014-09-01

    Snail, a zinc finger structure transcription inhibitory factor, has been reported to play an important role in the metastatic progression of several types of cancer. The aim of the study was to identify potential biomarkers for metastasis in gastrointestinal stromal tumors (GISTs) by examining the expression levels of Snail, E-cadherin, and Vimentin in GISTs and investigate their clinical significance. The protein expression of Snail, E-cadherin, and Vimentin in 74 GIST specimens was detected by immunohistochemical analysis, and the correlation between expression levels and clinicopathological data was analyzed. Snail, E-cadherin, and Vimentin were positively expressed in 51.4% (38/74), 32.4% (24/74), and 68.9% (51/74) of GIST tissue samples, respectively. Snail protein expression was significantly higher in GISTs with distant metastasis compared with GISTs without distant metastasis (P<0.05). E-cadherin expression level was significantly lower in cases of GIST with distant metastasis compared with those without distant metastasis (P<0.05), whereas the expression level of Vimentin did not significantly change according to clinical and pathological characteristics (all P>0.05). Snail expression was significantly negatively correlated with E-cadherin expression (r's=-0.276, P=0.017) but not with Vimentin expression (r's=0.041, P=0.728) in GISTs. High Snail expression and low E-cadherin expression were significantly correlated with metastasis in GISTs, and Snail, because of positive correlation, is potentially a biomarker of GIST with distant metastasis.

  9. Laparoscopic management of gastrointestinal stromal tumours: review at a Canadian centre

    PubMed Central

    Daigle, Carl; Meneghetti, Adam T.; Lam, Jasmine; Panton, Ormond N.M.

    2012-01-01

    Background Laparoscopic wedge resection has been widely accepted for small benign gastric tumours. Large gastrointestinal stromal tumours (GISTs), however, can be difficult to manipulate laparoscopically and are at risk for capsule disruption, which can then result in peritoneal seeding. Some authors have suggested that large GISTs (> 8 cm) are best approached using an open technique. However, there has been no consensus as to what the cut-off size should be. We conducted one of the largest Canadian series to date to assess outcomes and follow-up of the laparoscopic management of GISTs. Methods All patients with gastric GISTs presenting to Vancouver General Hospital and University of British Columbia Hospital between 2000 and 2008 were reviewed. Most lesions were resected using a wedge technique with closure of the stomach facilitated by an endoscopic linear stapling device. Results In all, 23 patients presented with GISTs; 19 patients underwent laparoscopic resection and, of these, 15 had a purely laparoscopic operation and 4 had a hand-assisted laparoscopic resection. Mean tumour size was 3.2 cm, with the largest tumour measuring 6.8 cm. There were no episodes of tumour rupture or spillage and no major intraoperative complications. All margins were negative. Mean follow-up was 13.3 (range 1–78) months. There was no evidence of recurrence or metastasis. Conclusion The laparoscopic management of gastric GISTs is safe and effective with short hospital stays and good results over a mean follow-up of 13.3 months. We believe that it should be the preferred technique offered to patients. PMID:22269221

  10. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

    PubMed Central

    Janeway, Katherine A.; Kim, Su Young; Lodish, Maya; Nosé, Vânia; Rustin, Pierre; Gaal, José; Dahia, Patricia L. M.; Liegl, Bernadette; Ball, Evan R.; Raygada, Margarita; Lai, Angela H.; Kelly, Lorna; Hornick, Jason L.; O'Sullivan, Maureen; de Krijger, Ronald R.; Dinjens, Winand N. M.; Demetri, George D.; Antonescu, Cristina R.; Fletcher, Jonathan A.; Helman, Lee; Stratakis, Constantine A.

    2011-01-01

    Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1–associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis. PMID:21173220

  11. Life-threatening bleeding of a duodenal gastrointestinal stromal tumor in a teenager: a rare case report

    PubMed Central

    Valli, Piero V.; Valli, Carlo; Pfammatter, Thomas; Bauerfeind, Peter

    2016-01-01

    Duodenal gastrointestinal stromal tumors (GIST) are per se infrequent and are exceptional in children or young adults. So far, only 2 cases of pediatric duodenal GISTs have been published. Here we report on the case of a 19-year-old female patient who was admitted in hemorrhagic shock due to arterial bleeding of a duodenal GIST located in immediate proximity to the major duodenal papilla. After several attempts of endoscopic hemostasis failed, the tumor bleeding was controlled with a second coil embolization of the pancreaticoduodenal arcades. PMID:27995183

  12. Is laparoscopic resection the appropriate management of a jejunal gastrointestinal stromal tumor (GIST)? Report of a case.

    PubMed

    Pitiakoudis, Michail; Zezos, Petros; Courcoutsakis, Nikos; Papanas, Nikolaos; Giatromanolaki, Alexandra; Sivridis, Efthimios; Kouklakis, Georgios; Simopoulos, Constantinos

    2010-10-01

    A 51-year-old female patient presented with iron deficiency anemia. Upper and lower gastrointestinal endoscopy were unremarkable. Computed tomography enteroclysis showed an ovoid 3×4-cm jejunal tumor with intraluminal protrusion and exophytic growth pattern, without lymphadenopathy or metastatic disease. Laparoscopic resection of the tumor was successfully carried out. Histologically, a mesenchymal tumor composed of spindle cells with an interlacing bundle pattern and high-mitotic activity greater than 10 mitoses/50 high-power fields were observed. The immunohistochemistry showed that the tumor was KIT (CD117)-, vimentin-, smooth muscle actin-, and S-100-positive, whereas it was CD34-negative. These findings were consistent with the features of a gastrointestinal stromal tumor. The patient had an uneventful postoperative course, and after 10 months of follow-up, she is well without any evidence of tumor recurrence.

  13. A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro).

    PubMed

    Vale Rodrigues, Rita; Santos, Filipa; Pereira da Silva, João; Francisco, Inês; Claro, Isabel; Albuquerque, Cristina; Lemos, Maria Manuel; Limbert, Manuel; Dias Pereira, António

    2017-04-01

    Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.

  14. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

    2012-07-15

    Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

  15. Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor

    PubMed Central

    2014-01-01

    Background Gastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease. Methods Fresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed. Results Herein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473±695-mm3 (median 199-mm3, range 12.6-2682.5-mm3) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also

  16. Gastrointestinal stromal tumor as entry port for S. intermedius causing bacteremia and multiple liver abscesses. Case report and review of literature.

    PubMed

    Benou, C; Walter, B M; Schlitter, M A; Wilhelm, D; Neu, B; Schmid, R M

    2016-03-01

    We report a case of a previously healthy 52-year-old man who presented with fever and liver lesions suspicious for metastatic disease, which proved subsequently to be abscesses. Further workup revealed a gastrointestinal stromal tumor (GIST) in the gastric corpus as entry port to Streptococcus intermedius-associated bacteremia and liver abscesses. After antibiotic treatment and surgical resection of the tumor, the patient recovered well. This unusual case indicates that gastrointestinal stromal tumors can remain undetected until they cause a life threatening infection. A review of recent literature pertaining to GIST and liver abscesses follows.

  17. The inside mystery of jejunal gastrointestinal stromal tumor: a rare case report and review of the literature.

    PubMed

    Dhull, A K; Kaushal, V; Dhankhar, R; Atri, R; Singh, H; Marwah, N

    2011-01-01

    Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA) has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.

  18. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  19. Splenosis in gastric fundus mimicking gastrointestinal stromal tumor: a report of two cases and review of the literature.

    PubMed

    Li, Bin; Huang, Ya; Chao, Baoting; Zhao, Qi; Hao, Jinghua; Qin, Chengyong; Xu, Hongwei

    2015-01-01

    Splenosis refers to heterotopic autotransplantation and implantation of splenic tissue following splenic trauma or surgery. Splenosis in gastric fundus is rare and difficult to diagnose, since splenosis has similar manifestation with gastrointestinal stromal tumor (GIST) under routine endoscopy examination. In this report, we present two quite rare case of splenosis. Both of their pre-operative diagnose under endoscopic ultrasonography was considered as GIST. Finally, one in the abdominal cavity, adhering closely to the gastric fundus, measuring 20 mm × 15 mm, was resected by surgical operation, and one in the gastric fundus, measuring 20 mm × 20 mm, was resected by endoscopic surgery. The precise diagnosis of splenosis was distinct by post-operative histopathologic examination. In addition, we also made a mini review of previously published articles, in order to provide indication to solve future doubts in diagnosing and treating splenosis.

  20. Gastrointestinal stromal tumor with a PDGFRA mutation masquerading as gastric plexiform fibromyxoma: A comparative clinicopathological study of two cases

    PubMed Central

    Zhou, Jun; Xu, Jingjing; Jiang, Guozhong; Ma, Yihui; Qi, Jingwen; Li, Wencai; Zhang, Dandan

    2017-01-01

    Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum. Histologically, the two cases shared a rare and approximately unanimous morphological pattern of a prominent multinodular and plexiform figuration in the gastric wall, including mucoid matrix, short spindle cells and small caliber vascular elements, and areas of stromal tumor cells exhibited an epithelioid appearance. Immunohistochemistry revealed that the PF tumor cells were positive for smooth muscle actin (SMA), but negative for mast/stem cell growth factor receptor (KIT), GIST-1 (DOG1), cluster of differentiation (CD) 34, S-100, desmin and cytokeratin AE1/AE3. The case of GIST expressed KIT and DOG1, but was negative for SMA, CD34, S-100, desmin and AE1/AE3. In addition, the GIST case, which was observed to harbor a D842V mutation in exon 18 of PDGFRA, was demonstrated to be genetically distinct from PF. The cases presented in the current study were uncommon in that GIST exhibited a plexiform appearance that mimicked the histology of the rare PF tumor; therefore, GIST must be considered and discounted first when determining a differential diagnosis for a gastrointestinal mesenchymal neoplasm. PMID:28356974

  1. Clinicopathologic study of 275 cases of gastrointestinal stromal tumors: the experience at 3 large medical centers in Mexico.

    PubMed

    Alvarado-Cabrero, Isabel; Vázquez, Gonzálo; Sierra Santiesteban, Francisca I; Hernández-Hernández, Dulce Ma; Pompa, Angel Zavala

    2007-02-01

    It is important to distinguish gastrointestinal (GI) stromal tumors (GISTs) from other GI mesenchymal tumors (GIMTs) because of the availability of molecular-targeted therapy for GISTs. The aim of the study was to reclassify GIMTs and to determine the clinicopathologic features of GISTs in Mexico. Cases of GIMT identified from the database of 3 large diagnostic centers in Mexico between 1995 and 2004 were reclassified according to current criteria. Hematoxylin and eosin-stained sections and clinical histories were reviewed, and immunohistochemistry was performed using anti-CD117, CD34, smooth muscle actin, and S-100 protein. A total of 275 GISTs were identified. The tumors were located in the stomach (40%), small intestine (35%), colorectum (12%), abdominal cavity (11%), and esophagus (2%). There were equal numbers of men and women with a mean age at diagnosis of 61 years. The tumors ranged in size from 3.5 to 34 cm (mean, 9.1 cm); 95 tumors (34%) were larger than 10 cm. Colorectal and omental tumors were the largest. The cell types included pure spindle (68%), pure epithelioid (16%), and mixed epithelioid/spindle (14%). Whereas 17.8% of tumors were regarded as low risk, 43% of tumors were in the high-risk category. CD117 positivity was detected in most of the tumors (96%). In addition to CD117, 255 cases (92%) were positive for CD34, 82 cases (32%) were positive for smooth muscle actin, and 13 cases (4.7%) were positive for desmin. Gastrointestinal stromal tumors in Mexico have the same clinicopathologic and immunohistochemical features as those reported in other countries. It is not always easy to distinguish GISTs from other soft tissue lesions. The diagnosis can be difficult even for experienced pathologists.

  2. [A case of metachronous gastrointestinal perforation of a patient with metastatic rectal cancer during treatment with bevacizumab-based chemotherapy].

    PubMed

    Sadatomo, Ai; Koinuma, Koji; Miki, Atsushi; Horie, Hisanaga; Yasuda, Yoshikazu

    2013-07-01

    A 64-year-old man received mFOLFOX6+bevacizumab chemotherapy for metastatic lung cancer after rectal cancer resection( Stage IV). After 28 courses, he had an abdominal pain with fever, and computed tomography showed pelvic abscess with stercolith of appendix. He was diagnosed as acute appendicitis with intra-abdominal abscess, and emergency appendectomy with drainage was performed. Two days after the operation, he was suspected to have a sutural leakage as was suggested from the properties of his drainage, therefore re-operation was performed. A small hole of the ileum, about 2mm in diameter, was observed. The margin of the hole showed neither inflammatory nor neoplastic change, and a suturing closure of the hole was performed. The post-operative course was uneventful. Histopathological findings of the resected appendix suggested that the perforation was caused by necrosis of metastatic cancer cells penetrating the appendiceal wall. This is a case of a bevacizumab-related metachronous perforation that occurred in different gastrointestinal origins within a very short term.

  3. A Foregut Duplication Cyst of the Stomach in Association with a Gastrointestinal Stromal Tumor and a Leiomyoma: A Case Report

    PubMed Central

    Gagné, Andréanne; Sazonova, Olga; Marceau, Simon; Périgny, Martine

    2016-01-01

    Objectives. Duplication cysts are rare benign lesions usually arising in the gastrointestinal tract. We report a case of a 52-year-old woman with an incidental gastric mass found on computed tomography during a pregraft workup for a familial cardiomyopathy. Methods. The mass was completely excised by partial gastrectomy and gross examination revealed a cystic lesion containing two small solid nodules in its wall. Microscopic evaluation and immunohistochemistry study were performed to further characterize the cyst and the nodules. A comprehensive literature review of the NCBI database PubMed was also carried out. Results. While the cyst was diagnosed as a foregut duplication cyst, the solid nodules proved to be concomitant gastrointestinal stromal tumor (GIST) and leiomyoma. Both morphologic features and immunohistochemistry stains, including CD117, smooth muscle actin, and CD34 supported the diagnosis. Clinical course was benign and the patient had no clinical evidence of relapse ten months following the surgical procedure. The literature search did not reveal any other published case of a foregut duplication cyst presenting in combination with a GIST and a leiomyoma. Conclusions. To our knowledge, this is the first case of a composite lesion comprising a foregut duplication cyst of the stomach along with a leiomyoma and a GIST. PMID:28097030

  4. Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting.

    PubMed

    Ponti, Giovanni; Luppi, Gabriele; Martorana, Davide; Rossi, Giulio; Losi, Lorena; Bertolini, Federica; Sartori, Giuliana; Pellacani, Giovanni; Seidenari, Stefania; Boni, Elisa; Neri, Tauro Maria; Silini, Enrico; Tamburini, Elisa; Maiorana, Antonio; Conte, Pier Franco

    2010-02-01

    Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic and inherited GISTs, a small subset of GISTs are negative for both. Besides the classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic disease. The present study was designed to analyze the synchronous and metachronous tumors developed among GIST patients assessed by our institution for GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and 64 women) were recruited between 1988 and 2007 and their clinical and pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR genes was performed on somatic and peripheral blood DNA. GISTs occurred associated with other primary malignancies in 46 of 141 (32.6%) patients. The most common neoplasms were gastrointestinal and genitourinary. A novel exon 6 germline large deletion of NF1 was identified in the NF1/GIST kindred. The development of GIST associated with other neoplasms is common and diagnosis of peculiar benign associated-neoplasms warrants the search for familial cancer susceptibility. In particular, syndromic or familial settings have to be suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA negative GIST patients.

  5. Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression

    PubMed Central

    Burgoyne, Adam M.; Leonard, Stephanie Y.; Gao, Fei; Chan, Jonathan C.; Shi, Eileen; Chmielecki, Juliann; Morosini, Deborah; Wang, Kai; Ross, Jeffrey S.; Kendrick, Michael L.; Bardsley, Michael R.; De Siena, Martina; Mao, Junhao; Harismendy, Olivier

    2016-01-01

    Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST. PMID:27793025

  6. High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study

    PubMed Central

    Giner, Francisco; Machado, Isidro; Lopez-Guerrero, Jose Antonio; Mayordomo-Aranda, Empar; Llombart-Bosch, Antonio

    2017-01-01

    Background Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice. Methods The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude mice using tissue microarrays (TMA). Tumour pieces were also implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed at 24, 48, and 96 h; and 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularisation experiments). Results Morphological similarities were apparent in the early stages of neoplastic growth of these two soft-tissue tumours throughout the passages in nude mice and in the two neovascularisation experiments. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors between 24 h and 96 h after xenotransplantation in both tumours. Additionally, neoplastic cells coexpressed chemokines (CXCL9, CXCL10, GRO, and CXCL12) and their receptors in both tumours. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion This model could provide information on the early stages of the angiogenic process in monophasic spindle cell SS and high-risk GIST and offers an excellent way to study possible tumour response to antiangiogenic drugs. PMID:28386296

  7. Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

    PubMed

    Pantaleo, M A; Landuzzi, L; Nicoletti, G; Nanni, C; Boschi, S; Piazzi, G; Santini, D; Di Battista, M; Castellucci, P; Lodi, F; Fanti, S; Lollini, P-L; Biasco, G

    2009-09-01

    The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

  8. Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors

    PubMed Central

    Zamò, Alberto; Bertolaso, Anna; Franceschetti, Ilaria; Weirich, Gregor; Capelli, Paola; Pecori, Sara; Chilosi, Marco; Hoefler, Heinz; Menestrina, Fabio; Scarpa, Aldo

    2007-01-01

    Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions ≥3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We propose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases. PMID:17384206

  9. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST) mimicking hereditary GIST syndromes

    PubMed Central

    Neves, Mafalda Costa; Stamp, Gordon; Mudan, Satvinder

    2015-01-01

    Introduction Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. Case report 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4 cm GIST in the gastric fundus. Pathology of the resected specimen revealed diffuse segmental ICC hyperplasia harbouring two macroscopic GISTs and a ‘tumorlet’. A mutation in c-KIT exon 11 was detected in both the solid and the diffuse components. Discussion ICC hyperplasia can occur either as a sporadic focal lesion or in a syndromic setting, known to predispose to multiple GIST tumours at different sites. The majority of cases of sporadic ICC hyperplasia previously reported were of localised type. The hereditary form is mostly caused by germline mutations in c-KIT and PDGFRA or in patients with NF-1 andpresents as a diffuse hyperplasia, usually with a confluent, nodular or multifocal growth pattern. Conclusion We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder. PMID:26521201

  10. Opposing roles of KIT and ABL1 in the therapeutic response of gastrointestinal stromal tumor (GIST) cells to imatinib mesylate.

    PubMed

    Rausch, Jessica L; Boichuk, Sergei; Ali, Areej A; Patil, Sneha S; Liu, Lijun; Lee, Donna M; Brown, Matthew F; Makielski, Kathleen R; Liu, Ying; Taguchi, Takahiro; Kuan, Shih-Fan; Duensing, Anette

    2017-01-17

    Most gastrointestinal stromal tumors (GISTs) are caused by activating mutations of the KIT receptor tyrosine kinase. The small molecule inhibitor imatinib mesylate was initially developed to target the ABL1 kinase, which is constitutively activated through chromosomal translocation in BCR-ABL1-positive chronic myeloid leukemia. Because of cross-reactivity of imatinib against the KIT kinase, the drug is also successfully used for the treatment of GIST. Although inhibition of KIT clearly has a major role in the therapeutic response of GIST to imatinib, the contribution of concomitant inhibition of ABL in this context has never been explored. We show here that ABL1 is expressed in the majority of GISTs, including human GIST cell lines. Using siRNA-mediated knockdown, we demonstrate that depletion of KIT in conjunction with ABL1 - hence mimicking imatinib treatment - leads to reduced apoptosis induction and attenuated inhibition of cellular proliferation when compared to depletion of KIT alone. These results are explained by an increased activity of the AKT survival kinase, which is mediated by the cyclin-dependent kinase CDK2, likely through direct phosphorylation. Our results highlight that distinct inhibitory properties of targeted agents can impede antitumor effects and hence provide insights for rational drug development. Novel KIT-targeted agents to treat GIST should therefore comprise an increased specificity for KIT while at the same time displaying a reduced ability to inhibit ABL1.

  11. First Case Report of a Sporadic Adrenocortical Carcinoma With Gastric Metastasis and a Synchronous Gastrointestinal Stromal Tumor of the Stomach.

    PubMed

    Kovecsi, Attila; Jung, Ioan; Bara, Tivadar; Bara, Tivadar; Azamfirei, Leonard; Kovacs, Zsolt; Gurzu, Simona

    2015-09-01

    Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases. A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 × 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified. So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously.

  12. The diagnostic value of endoscopic ultrasonography and contrast-enhanced harmonic endoscopic ultrasonography in gastrointestinal stromal tumors

    PubMed Central

    Zhao, Yanchao; Qian, Linxue; Li, Peng; Zhang, Shutian

    2016-01-01

    Objective: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) and contrast-enhanced harmonic (CEH) EUS in patients with gastrointestinal stromal tumors (GISTs). Patients and Methods: About 19 patients with suspected GISTs underwent EUS and CEH-EUS before tumor resection. The malignant potential was assessed according to the modified Fletcher classification system. Patients were divided into lower (Group I) and higher (Group II) malignant potential group. The clinical characteristics and EUS/CEH-EUS features were compared between two groups. Results: The tumor size in Group II was significantly larger than that in Group I (14.6 ± 5.8 mm vs. 32.1 ± 8.4 mm, P < 0.05). Heterogeneous echogenicity was observed in 4 (4/8) cases in Group II and none in Group I (P < 0.05). Irregular intratumoral vessels were detected in 6 cases in Group II and none in Group I (P < 0.05). The sensitivity and specificity of irregular vessel detection for discriminating higher from lower malignant potential GISTs were 75% and 100%, respectively. The positive predictive value and negative predictive value of detection of irregular vessels to high malignant potential GISTs were 33% and 100%, respectively. Conclusion: Detection of irregular intratumoral vessels can predict higher malignant potential before tumor resection. The tumor size and echogenicity are assistant factors for malignant potential assessment. Endoscopic resection is an efficacious treatment with good security for appropriate patients. PMID:27080610

  13. Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review

    PubMed Central

    Congedo, Teresa; Ricci, Riccardo; Martini, Maurizio; Di Noia, Vincenzo; Di Dio, Carmela; Quirino, Michela; Barone, Carlo; Cassano, Alessandra

    2017-01-01

    Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment. PMID:28280629

  14. Epithelial and Stromal Cell Urokinase Plasminogen Activator Receptor Expression Differentially Correlates with Survival in Rectal Cancer Stages B and C Patients

    PubMed Central

    Ahn, Seong Beom; Chan, Charles; Dent, Owen F.; Mohamedali, Abidali; Kwun, Sun Young; Clarke, Candice; Fletcher, Julie; Chapuis, Pierre H.; Nice, Edouard C.; Baker, Mark S.

    2015-01-01

    Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC. PMID:25692297

  15. The HSP90 Inhibitor, AT13387, Is Effective against Imatinib-Sensitive and -Resistant Gastrointestinal Stromal Tumor Models

    PubMed Central

    Smyth, Tomoko; Van Looy, Thomas; Curry, Jayne E.; Rodriguez-Lopez, Ana M.; Wozniak, Agnieszka; Zhu, Meijun; Donsky, Rachel; Morgan, Jennifer G.; Mayeda, Mark; Fletcher, Jonathan A.; Schöffski, Patrick; Lyons, John; Thompson, Neil T.; Wallis, Nicola G.

    2013-01-01

    The majority of gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT, an HSP90 client protein. Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibition might be a valuable treatment option for GIST, which would be equally effective on imatinib-sensitive and -resistant clones. We investigated the activity of AT13387, a potent HSP90 inhibitor currently being evaluated in clinical trials, in both in vitro and in vivo GIST models. AT13387 inhibited the proliferation of imatinib-sensitive (GIST882, GIST-T1) and -resistant (GIST430, GIST48) cell lines, including those resistant to the geldanamycin analogue HSP90 inhibitor, 17-AAG. Treatment with AT13387 resulted in depletion of HSP90 client proteins, KIT and AKT, along with their phospho-forms in imatinib-sensitive and -resistant cell lines, irrespective of KIT mutation. KIT signaling was ablated, whereas HSP70, a marker of HSP90 inhibition, was induced. In vivo, antitumor activity of AT13387 was showed in both the imatinib-sensitive, GIST-PSW, xenograft model and a newly characterized imatinib-resistant, GIST430, xenograft model. Induction of HSP70, depletion of phospho-KIT and inhibition of KIT signaling were seen in tumors from both models after treatment with AT13387. A combination of imatinib and AT13387 treatment in the imatinib-resistant GIST430 model significantly enhanced tumor growth inhibition over either of the monotherapies. Importantly, the combination of AT13387 and imatinib was well tolerated. These results suggest AT13387 is an excellent candidate for clinical testing in GIST in combination with imatinib. PMID:22714264

  16. Gastrointestinal stromal tumors (GIST): a rare entity, a tumor model for personalized therapy, and yet ten different molecular subtypes.

    PubMed

    Blay, Jean-Yves; Le Cesne, Axel; Cassier, Philippe A; Ray-Coquard, Isabelle L

    2012-05-01

    Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma and were recognized as distinct molecular entities in 1998. Following the identification of driving molecular alterations in KIT, imatinib was rapidly introduced for the treatment of GIST, and became the paradigm of molecularly targeted therapies for solid tumors. While surgery was the only known effective treatment in 1998, two drugs are approved by the FDA and EMA in 2012 for the treatment of localized and advanced forms of this disease. Imatinib has been shown to provide a high level of clinical efficacy in patients with advanced GIST, a median progression-free survival (PFS) of 2 years and median overall survival close to 5 years, with 20% patients progression-free after 10 years of treatment. Imatinib has also been proven to improve overall survival and reduce the risk of relapse in localized GIST at high risk for relapse after resection. Sunitinib is indicated in advanced GIST after failure of imatinib, and provided a median PFS close to 6 months after imatinib failure. However, there is an important variability in the molecular and genetic characteristics that drive the pathogenesis of GIST, allowing thus for the identification of distinct molecular subtypes of GIST with different prognosis and sensitivity to the targeted treatments. Different strategies are now recommended in these different molecular subtypes of GIST which must be recognized as different entities regarding sensitivity to tyrosine kinase inhibitors and treatment decisions. This fragmentation of a yet recently recognized disease entity illustrates to strong trend of fragmentation in nosology of cancers, even in rare tumors such as GIST. For this aspect also, GIST is again a paradigmatic model for oncology, as many tumors with a higher prevalence will be fragmented in different molecular subsets and are going to become rare disease in the years to come.

  17. Antitumor effect of the tyrosine kinase inhibitor nilotinib on gastrointestinal stromal tumor (GIST) and imatinib-resistant GIST cells.

    PubMed

    Sako, Hiroyuki; Fukuda, Kazumasa; Saikawa, Yoshiro; Nakamura, Rieko; Takahashi, Tsunehiro; Wada, Norihito; Kawakubo, Hirohumi; Takeuchi, Hiroya; Ohmori, Tai; Kitagawa, Yuko

    2014-01-01

    Despite the benefits of imatinib for treating gastrointestinal stromal tumors (GIST), the prognosis for high risk GIST and imatinib-resistant (IR) GIST remains poor. The mechanisms of imatinib resistance have not yet been fully clarified. The aim of the study was to establish imatinib-resistant cell lines and investigate nilotinib, a second generation tyrosine kinase inhibitor (TKI), in preclinical models of GIST and imatinib-resistant GIST. For a model of imatinib-resistant GIST, we generated resistant cells from GK1C and GK3C cell lines by exposing them to imatinib for 6 months. The parent cell lines GK1C and GK3C showed imatinib sensitivity with IC50 of 4.59±0.97 µM and 11.15±1.48 µM, respectively. The imatinib-resistant cell lines GK1C-IR and GK3C-IR showed imatinib resistance with IC50 values of 11.74±0.17 µM (P<0.001) and 41.37±1.07 µM (P<0.001), respectively. The phosphorylation status of key cell signaling pathways, receptor tyrosine kinase KIT (CD117), platelet-derived growth factor receptor alpha (PDGFRA) and downstream signaling kinases: serine-threonine kinase Akt (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) or the non-receptor tyrosine kinase: proto-oncogene tyrosine-protein kinase Src (SRC), was analyzed in established cell lines and ERK1/2 phosphorylation was found to be increased compared to the parental cells. Nilotinib demonstrated significant antitumor efficacy against GIST xenograft lines and imatinib-resistant GIST cell lines. Thus, nilotinib may have clinical potential for patients with GIST or imatinib-resistant GIST.

  18. Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome

    PubMed Central

    Angelini, Sabrina; Ravegnini, Gloria; Nannini, Margherita; Bermejo, Justo Lorenzo; Musti, Muriel; Pantaleo, Maria A; Fumagalli, Elena; Venturoli, Nicola; Palassini, Elena; Consolini, Nicola; Casali, Paolo G; Biasco, Guido; Hrelia, Patrizia

    2015-01-01

    The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05–0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014–0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77–26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population. PMID:25227144

  19. Successful establishment of patient-derived tumor xenografts from gastrointestinal stromal tumor-a single center experience

    PubMed Central

    Jiang, Quan; Tong, Han-Xing; Zhang, Yong; Hou, Ying-Yong; Li, Jing-Lei; Wang, Jiong-Yuan; Zhou, Yu-Hong; Lu, Wei-Qi

    2016-01-01

    Patient-derived tumor xenografts (PDTX) generally represent a kind of more reliable model of human disease, by which a potential drugs’ preclinical efficacy could be evaluated. To date, no stable gastrointestinal stromal tumor (GIST) PDTX models have been reported. In this study, we aimed to establish stable GIST PDTX models and to evaluate whether these models accurately reflected the histological feature of the corresponding patient tumors and create a reliable GIST PDTX models for our future experiment. By engrafting fresh patient GIST tissues into immune-compromised mice (BALB/c athymic mice), 4 PDTX models were established. Histological features were assessed by a qualified pathologist based on H&E staining, CD117 and DOG-1. We also conduct whole exome sequencing(WES) for the 4 established GIST PDTX models to test if the model still harbored the same mutation detected in corresponding patient tumors and get a more intensive vision for the genetic profile of the models we have established, which will help a lot for our future experiment. To explore the tumorigenesis mechanism for GIST, we also have a statistical analysis for the genes detected as nonsynchronous-mutated simultaneously in 4 samples. All 4 GIST PDTX models retained the histological features of the corresponding human tumors, with original morphology type and positive stains for CD117 and DOG-1. Between the GIST PDTX models and their parental tumors, a same mutation site was detected, which confirmed the genetic consistency. The stability of molecular profiles observed within the GIST PDTX models provides confidence in the utility and translational significance of these models for in vivo testing of personalized therapies. To date, we conducted the first study to successfully establish a GIST PDTX model whose genetic profiles were revealed by whole exome sequencing. Our experience could be of great use. PMID:27186422

  20. Comparison of Different Risk Classification Systems in 558 Patients with Gastrointestinal Stromal Tumors after R0-Resection

    PubMed Central

    Schmieder, Michael; Henne-Bruns, Doris; Mayer, Benjamin; Knippschild, Uwe; Rolke, Claudia; Schwab, Matthias; Kramer, Klaus

    2016-01-01

    Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection. Methods: Tumor size, mitotic count and site were used in variable combination to predict high- and low risk patients by the use of the five risk classification models. For survival analyses disease-specific survival, disease-free survival and overall-survival were investigated. Patients with initial metastatic disease or incompletely resectable tumors were excluded. Results: All GIST classification models distinguished well between patients with high-risk and low-risk tumors and none of the five risk systems was superior to predict patient outcome. The models showed significant heterogeneity. There was no significant difference between the different risk-groups regarding overall-survival. Subdivision of GIST patients with very low- and low-risk appeared to be negligible. Conclusions: Currently applied GIST risk classification systems are comparable to predict high- or low-risk patients with initial non-metastatic and completely resected GIST. However, the heterogeneity of the high-risk group and the absence of differences in overall survival indicate the need for more precise tumor- and patient-related criteria for better stratification of GIST and identification of patients who would benefit best from adjuvant tyrosine kinase inhibitor therapy. PMID:28082898

  1. Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors

    PubMed Central

    Hsueh, Yuan-Shuo; Yen, Chueh-Chuan; Shih, Neng-Yao; Chiang, Nai-Jung; Li, Chien-Feng; Chen, Li-Tzong

    2013-01-01

    Gastrointestinal stromal tumor (GIST) is a prototype of mutant KIT oncogene-driven tumor. Prolonged tyrosine kinase inhibitor (TKI) treatment may result in a resistant phenotype through acquired secondary KIT mutation. Heat shock protein 90 (HSP90AA1) is a chaperone protein responsible for protein maturation and stability, and KIT is a known client protein of HSP90AA1. Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway. In this study, we demonstrated that NVP-AUY922 (AUY922), a new class of HSP90AA1 inhibitor, is effective in inhibiting the growth of GIST cells expressing mutant KIT protein, the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells. The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines. Surprisingly, AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway. The blockade of autophagy alone led to the accumulation of the KIT protein, highlighting the role of autophagy in endogenous KIT turnover. The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B-, acridine orange- or SQSTM1-labeled autophagosome, and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity. Therefore, the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs, but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation. PMID:23196876

  2. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors.

    PubMed

    Agaram, Narasimhan P; Wong, Grace C; Guo, Tianhua; Maki, Robert G; Singer, Samuel; Dematteo, Ronald P; Besmer, Peter; Antonescu, Cristina R

    2008-10-01

    BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis. Alterations in RAS/MEK/ERK pathway may also be involved in development of imatinib resistance in GIST, particularly in tumors lacking secondary KIT or PDGFRA mutations. Imatinib-naive wild-type GISTs from 61 patients, including 15 children and 28 imatinib-resistant tumors without secondary KIT mutations were analyzed. Screening for hot spots mutations in BRAF (exons 11 and 15) and NRAS (exons 2 and 3) was performed. A BRAF exon 15 V600E was identified in 3 of 61 GIST patients, who shared similar clinical features, being 49- to 55-years-old females and having their tumors located in the small bowel. The tumors were strongly KIT immunoreactive and had a high risk of malignancy. An identical V600E BRAF mutation was also identified in one of 28 imatinib resistant GIST lacking a defined mechanism of drug resistance. In conclusion, we identified a primary BRAF V600E mutations in 7% of adult GIST patients, lacking KIT/PDGFRA mutations. The BRAF-mutated GISTs show predilection for small bowel location and high risk of malignancy. A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.

  3. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    PubMed Central

    Shinagare, Atul B.; Krajewski, Katherine M.; Pyo, Junhee; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. Materials and Methods In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. Results The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Conclusion Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. PMID:25741192

  4. Analysis of the amount of tissue sample necessary for mitotic count and Ki-67 index in gastrointestinal stromal tumor sampling.

    PubMed

    Kobara, Hideki; Mori, Hirohito; Rafiq, Kazi; Fujihara, Shintaro; Nishiyama, Noriko; Chiyo, Taiga; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Kato, Kiyohito; Kamada, Hideki; Fujita, Koji; Morishita, Asahiro; Oryu, Makoto; Tsutsui, Kunihiko; Iwama, Hisakazu; Kushida, Yoshio; Haba, Reiji; Masaki, Tsutomu

    2015-01-01

    There are no established opinions concerning whether the amount of tissue affects the accuracy of histological analyses in gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the appropriate amount of tissue sample needed for mitotic count based on the risk classification of GISTs and the Ki-67 index using the following three methods: endoscopic ultrasound-guided fine-needle aspiration (FNA), a novel sampling method called tunneling bloc biopsy (TBB), and biopsy forceps followed by TBB (Bf). Forty-three samples (12 FNA, 17 TBB and 14 Bf) diagnosed as GISTs by immunohistological analysis were utilized. The major and minor axes and overlay area of one piece of specimen (OPS) from the three sampling methods were measured using digital imaging software and were analyzed comparatively regarding the acquisition of histological data. The mean major and minor axes (mm) and overlay areas (mm2) were in the order of TBB > Bf > FNA. The evaluable rates by mitotic count and Ki-67 were, respectively, 75% (9/12) and 83.3% (10/12) for FNA samples, 100% (17/17) and 100% (17/17) for TBB samples, and 100% (14/14) and 100% (14/14) for Bf samples (P>0.05). Three FNA samples were judged unevaluable due to too small specimens in overall diagnosis including mitotic count and Ki-67, calculating the cut-off value for the overlay area of OPS as 0.17 mm2. Comparing the concordance rates between the pre- and post-operative samples, TBB samples was significantly better than FNA (P<0.05). Conclusively, while the amounts of tissues obtained by TBB and Bf are unnecessary for the histological assessment of mitotic count and Ki-67 index, developments of the FNA method are needed to minimize sample error. Considering the technical aspects, as well as the size of the specimens, could help to guide therapeutic planning and improve diagnostic yield for GI subepithelial tumors.

  5. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors1234

    PubMed Central

    Kramer, K.; Wolf, S.; Mayer, B.; Schmidt, S.A.; Agaimy, A.; Henne-Bruns, D.; Knippschild, U.; Schwab, M.; Schmieder, M.

    2015-01-01

    Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted. PMID:25622906

  6. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  7. Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation.

    PubMed

    Miettinen, Markku; Killian, Jonathan Keith; Wang, Zeng-Feng; Lasota, Jerzy; Lau, Christopher; Jones, Laura; Walker, Robert; Pineda, Marbin; Zhu, Yuelin Jack; Kim, Su Y; Helman, Lee; Meltzer, Paul

    2013-02-01

    A subset (7% to 10%) of gastric gastrointestinal stromal tumors (GISTs) is notable for the immunohistochemical loss of succinate dehydrogenase (SDH) subunit B (SDHB), which signals the loss of function of the SDH complex consisting of mitochondrial inner membrane proteins. These SDH-deficient GISTs are known to be KIT/PDGFRA wild type, and most patients affected by this subset of GISTs are young. Some of these patients have germline mutations of SDH subunit genes SDHB, SDHC, or SDHD, known as Carney-Stratakis syndrome when combined with paraganglioma. More recently, germline mutations in SDH subunit A gene (SDHA) have also been reported in few patients with KIT/PDGFRA wild-type GISTs. In this study we immunohistochemically examined 127 SDHB-negative and 556 SDHB-positive gastric GISTs and 261 SDHB-positive intestinal GISTs for SDHA expression using a mouse monoclonal antibody 2E3 (Abcam). Cases with available DNA were tested for SDHA, SDHB, SDHC, and SDHD gene mutations using a hybridization-based custom capture next-generation sequencing assay. A total of 36 SDHA-negative GISTs (28%) were found among 127 SDHB-negative gastric GISTs. No SDHB-positive GIST was SDHA negative. Among 7 SDHA-negative tumors analyzed, there were 7 SDHA mutants, most germline. A second hit indicating biallelic inactivation of SDHA was present in 6 of those cases. These patients had no other SDH subunit gene mutations. Among the 25 SDHA-positive, SDHB-negative GISTs analyzed, we identified 3 SDHA mutations (1 germline), and 11 SDHB, SDHC, or SDHD mutations (mostly germline), and 11 patients with no SDH mutations. Compared with patients with SDHA-positive GISTs, those with SDHA-negative GISTs had an older median age (34 vs. 21 y), lower female to male ratio (1.8 vs. 3.1) but similar mitotic counts and median tumor sizes, with a slow course of disease in most cases, despite a slightly higher rate of liver metastases. SDHA-negative GISTs comprise approximately 30% of SDHB

  8. Low Rectal Cancer Study (MERCURY II)

    ClinicalTrials.gov

    2016-03-11

    Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

  9. [Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and medical therapy. Developed during the 10th German GIST-meeting, Göttingen].

    PubMed

    Agaimy, A; Bauer, S; Beham, A; Bertolini, J; Haller, F; Koschny, R; Maier, J; Montemurro, M; Perez, D; Schaefer, I-M; Schildhaus, H-U; Wurst, C; Cameron, S

    2015-03-01

    The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.

  10. Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Takahashi, Tohru; Maruyama, Yumiko; Saitoh, Mayuko; Itoh, Hideto; Yoshimoto, Mitsuru; Tsujisaki, Masayuki; Nakayama, Masato

    2016-01-01

    A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved. PMID:27746431

  11. Successful treatment of bleeding large duodenal gastrointestinal stromal tumour in a patient under dual antiplatelet therapy after recent drug-eluting coronary stent implantation

    PubMed Central

    Fukuyama, Keita; Fujikawa, Takahisa; Kuramitsu, Shoichi; Tanaka, Akira

    2014-01-01

    We report a case of a 69-year-old man who started dual antiplatelet therapy (APT) with aspirin and clopidogrel after recent implantation of drug-eluting coronary stent and developed massive bleeding due to large duodenal gastrointestinal stromal tumour (GIST). Following endoscopic haemostasis and discontinuation of dual APT, neoadjuvant chemotherapy with imatinib was started under continuation of ‘single’ APT with aspirin. A good chemotherapeutic response was achieved without recurrence of bleeding, and subsequent less invasive surgical resection of the tumour was performed, while preoperative single APT was continued for prevention of stent thrombosis. The patient recovered well without any thromboembolic or bleeding events. Neoadjuvant imatinib therapy and subsequent less invasive surgery under continuation of APT is one of the preferred approaches for patients with duodenal GIST with severe thromboembolic comorbidities, as in the current case. PMID:24777088

  12. Rectal cancer: a review

    PubMed Central

    Fazeli, Mohammad Sadegh; Keramati, Mohammad Reza

    2015-01-01

    Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail. PMID:26034724

  13. Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors.

    PubMed

    Yan, Weixin; Zhang, Aiguo; Powell, Michael J

    2016-07-21

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identification of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the efficacy of cancer therapy by matching targeted drugs to specific mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by the KIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target amplification technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived "driver" and "drug-resistant" alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called "liquid biopsy" allows for the dynamic monitoring of the patients' tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR amplification of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.

  14. Kit K641E oncogene up-regulates Sprouty homolog 4 and Trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumours

    PubMed Central

    Gromova, Petra; Ralea, Sebastian; Lefort, Anne; Libert, Frédérick; Rubin, Brian P; Erneux, Christophe; Vanderwinden, Jean-Marie

    2009-01-01

    Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the KitK641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43, Gpc6, Gpr133, Pacrg, Pde3a, Prkar2b, Prkcq/Pkce, Rasd2, Spry4 and Tpbg/5T4 were found to be up-regulated. The proteins encoded by Gja1/Cx43, Pde3a, Prkcq/Pkce were localized in Kit-ir ICC in wild-type and KitK641E animals while Spry4 and Tpbg/5T4 were detected in Kit-ir cells only in KitK641E, but not in KitWT/WT animals. Most up-regulated genes in this mouse model belong to the gene expression profile of human GIST but also to the profile of normal Kit+ ICC in the mouse small intestine. Spry4 and Tpbg/5T4 may represent candidates for targeted therapeutic approaches in GIST with oncogenic KIT mutations. PMID:19453770

  15. Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy

    PubMed Central

    Costa Neves, Mafalda; Giakoustidis, Alexandros; Benson, Charlotte

    2015-01-01

    Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free. PMID:26075122

  16. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group.

    PubMed

    Kalkmann, Janine; Zeile, Martin; Antoch, Gerald; Berger, Frank; Diederich, Stefan; Dinter, Dietmar; Fink, Christian; Janka, Rolf; Stattaus, Jörg

    2012-05-07

    The aim was to reach consensus in imaging for staging and follow-up as well as for therapy response assessment in patients with gastrointestinal stromal tumours (GIST). The German GIST Imaging Working Group was formed by 9 radiologists engaged in assessing patients with GIST treated with targeted therapy. The following topics were discussed: indication and optimal acquisition techniques of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT; tumour response assessment considering response criteria and measurement techniques on CT, MRI and PET/CT; result interpretation; staging interval and pitfalls. Contrast-enhanced CT is the standard method for GIST imaging. MRI is the method of choice in case of liver-specific questions or contraindications to CT. PET/CT should be used for early response assessment or inconclusive results on morphologic imaging. All imaging techniques should be standardized allowing a reliable response assessment. Response has to be assessed with respect to lesion size, lesion density and appearance of new lesions. A critical issue is pseudoprogression due to myxoid degeneration or intratumoural haemorrhage. The management of patients with GIST receiving a targeted therapy requires a standardized algorithm for imaging and an appropriate response assessment with respect to changes in lesion size and density.

  17. Comparison of Gene Expression Profile Between Tumor Tissue and Adjacent Non-tumor Tissue in Patients with Gastric Gastrointestinal Stromal Tumor (GIST).

    PubMed

    Kou, Youwei; Zhao, Ying; Bao, Chenhui; Wang, Qiang

    2015-06-01

    Gastrointestinal stromal tumors (GISTs) are defined as spindle cell and/or epithelioid tumors originated from interstitial Cajal cells or precursors in the digestive tract. This study was conducted to identify genes differing in expression between the gastric tumors and the adjacent non-cancerous mucosas in patients with primary gastric GIST. The gene expression profile was determined by using oligonucleotide-based DNA microarrays and further validated by quantitative real-time PCR. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was performed to predict signaling pathways involved in gastric GIST. Our data showed that the expression levels of 957 genes (RAB39B, member RAS oncogene family; VCAN, versican; etc.) were higher and that of 526 genes (CXCL14, chemokine C-X-C motif ligand 14; MTUS1, microtubule-associated tumor suppressor 1; etc.) were lower in the gastric tumor tissues as compared with normal gastric tissues. Results from KEGG pathway analysis revealed that the differentially expressed genes were enriched into 16 signaling transduction pathways, including Hedeghog and Wnt signaling pathways. Our study may provide basis for identification of novel biomarkers associated with primary gastric GIST pathogenesis and for exploration of underlying mechanisms involved in this gastric sarcoma.

  18. Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism: first case series in patients with gastrointestinal stromal tumor

    PubMed Central

    Saif, Muhammad Wasif; Smith, Melissa Hennessey; Maloney, Antonia; Diasio, Robert B.

    2016-01-01

    Imatinib, an orally administered protein-tyrosine kinase inhibitor (TKI) is indicated for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Severe hepatotoxicity associated with imatinib is rare, and relationship to polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression and related frequency of hyperbilirubinemia or toxicity are not well known. We present a case series patients who developed hyperbilirubinemia while on oral administration imatinib for treatment of GIST. Genetic testing for polymorphism of UGT1A1 showed the first patient to be homozygous for the UGT1A1 TA7 (*28) polymorphism and the second patient heterozygous for the UGT1A1 TA1 (*28) polymorphism. The first patient had to stop imatinib due to severe and persistent hyperbilirubenemia peaking >3 despite reducing imatininb to only 100 mg every other day while the second patient improved at this dose. Our case series represent the first data associating UGT1A1 polymorphism and imatinib in patients being treated for GIST. Given the prevalence of Gilbert’s syndrome and the increasing use of imatinib, we encourage physicians to be aware of this possible toxicity as hepatotoxicity can be fatal if not managed in a timely fashion. This association is also timely due to recent FDA requirement for testing UGT1A1 polymorphism for nilotinib, another TKI. PMID:27708529

  19. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing.

    PubMed

    Pantaleo, Maria A; Astolfi, Annalisa; Indio, Valentina; Moore, Richard; Thiessen, Nina; Heinrich, Michael C; Gnocchi, Chiara; Santini, Donatella; Catena, Fausto; Formica, Serena; Martelli, Pier Luigi; Casadio, Rita; Pession, Andrea; Biasco, Guido

    2011-06-22

    Approximately 10%-15% of gastrointestinal stromal tumors (GISTs) in adults do not harbor any mutation in the KIT or PDGFRA genes (ie, KIT/PDGFRA wild-type GISTs). Recently, mutations in SDHB and SDHC (which encode succinate dehydrogenase subunits B and C, respectively) but not in SDHA and SDHD (which encode subunits A and D, respectively) were identified in KIT/PDGFRA wild-type GISTs. To search for novel pathogenic mutations, we sequenced the tumor transcriptome of two young adult patients who developed sporadic KIT/PDGFRA wild-type GISTs by using a massively parallel sequencing approach. The only variants identified as disease related by computational analysis were in SDHA. One patient carried the homozygous nonsense mutation p.Ser384X, the other patient was a compound heterozygote harboring a p.Arg31X nonsense mutation and a p.Arg589Trp missense mutation. The heterozygous nonsense mutations in both patients were present in germline DNA isolated from peripheral blood. Protein structure analysis indicates that all three mutations lead to functional inactivation of the protein. This is the first report, to our knowle dge, that identifies SDHA inactivation as a common oncogenic event in GISTs that lack a mutation in KIT and PDGFRA.

  20. Robotic Versus Laparoscopic Gastric Resection for Primary Gastrointestinal Stromal Tumors >5 cm: A Size-Matched and Location-Matched Comparison.

    PubMed

    de'Angelis, Nicola; Genova, Pietro; Amiot, Aurelien; Charpy, Cecile; Disabato, Mara; Belgaumkar, Ajay P; Chahrour, Ali; Legou, Francois; Azoulay, Daniel; Brunetti, Francesco

    2017-02-01

    This study compared robotic (RR) and laparoscopic resection (LR) for primary gastrointestinal stromal tumors (GISTs) of the stomach >5 cm. Twelve consecutive patients who underwent RR from 2012 to 2015 were matched for tumor size and location with 24 patients who underwent LR from 2000 to 2012. The median tumor size was 7.1 cm (range, 5.5 to 11.5). GISTs were resected by wedge resection (91.7%) or distal gastrectomy. The median RR operative time was longer than that of LR (162.5 vs. 130 min, respectively; P=0.004). Only 1 LR patient required conversion. The time to flatus and hospital stay were similar between groups. Overall, 3 patients developed minor postoperative complications that were medically treated. Mortality was nil. All resections were R0. No difference was observed in the incidence of recurrence. RR was significantly more expensive (+21.6%) than LR. RR appears to be safe and feasible for GISTs>5 cm, but is associated with longer operative times and greater costs.

  1. Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy.

    PubMed

    Neofytou, Kyriakos; Costa Neves, Mafalda; Giakoustidis, Alexandros; Benson, Charlotte; Mudan, Satvinder

    2015-01-01

    Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free.

  2. Chemical modifications in the seed region of miRNAs 221/222 increase the silencing performances in gastrointestinal stromal tumor cells.

    PubMed

    Durso, Montano; Gaglione, Maria; Piras, Linda; Mercurio, Maria Emilia; Terreri, Sara; Olivieri, Michele; Marinelli, Luciana; Novellino, Ettore; Incoronato, Mariarosaria; Grieco, Paolo; Orsini, Gaetano; Tonon, Giancarlo; Messere, Anna; Cimmino, Amelia

    2016-03-23

    Most GastroIntestinal Stromal Tumors (GISTs) are characterized by KIT gene overexpression, which in turn is regulated by levels of microRNA 221 and microRNA 222. GISTs can also be distinguished by their miRNAs expression profile in which miRNAs 221/222 result reduced in comparison with GI normal tissues. In this paper, to restore normal miRNAs levels and to improve the silencing performances of miRNAs 221/222, new miRNA mimics in which guide strands are modified by Phosphorothioate (PS) and/or 2'-O-methyl RNA (2'-OMe) inside and outside the seed region, were synthesized and tested in GIST48 cells. We evaluated the positional effect of the chemical modifications on the miRNAs silencing activity, compared to natural and several commercial miRNA mimics. Our results show that chemically modified miRNAs 221/222 with alternating 2'-OMe-PS and natural nucleotides in the seed region are effective inhibitors of KIT gene expression and exhibit increased stability in rat plasma. Besides, their transfection in GIST 48 cells showed significant effects on different cellular processes in which KIT plays a functional role for tumor development (such as migration, cell proliferation, and apoptosis). Therefore, modified miRNAs 221/222 may provide an alternative therapeutic option for GIST treatment also aimed to overcome drug resistance concerns.

  3. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  4. Treatment of non-resectable and metastatic gastrointestinal stromal tumors: experience with the use of tyrosine kinase inhibitors in a third level hospital in Mexico

    PubMed Central

    Pimentel Renteria, Alberto; Pluma Jiménez, Miguel; Pérez Martínez, Mario; Martínez Martínez, Gloria; Rivera Rivera, Samuel; Grajales Álvarez, Rocío; Bautista Aragón, Yolanda; Quintana Quintana, Miguel; Alejandro Silva, Juan

    2016-01-01

    Background Stromal tumors of the digestive tract are uncommon malignant diseases, are subclassified as leiomyosarcomas and Gastrointestinal Stromal Tumors (GIST) depending on the molecular expression of tyrosine kinase receptor KIT (CD117). GISTs represent 1% of malignant tumors affecting this anatomical site. Localized tumours diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since tyrosine kinase inhibitors (TKIs) were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results We obtained information of 71 patients with metastatic, non-resectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%) with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%), most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 30.6 months and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400 mg per day. Treatment was well-tolerated in most cases. Conclusions Metastatic GIST evaluated in our center shows a different affection in gender and age, and our population shows a different response to TKIs

  5. Transanal endoscopic microsurgery as optimal option in treatment of rare rectal lesions: A single centre experience

    PubMed Central

    Ortenzi, Monica; Ghiselli, Roberto; Cappelletti Trombettoni, Maria Michela; Cardinali, Luca; Guerrieri, Mario

    2016-01-01

    AIM To analyze the outcomes of transanal endoscopic microsurgery (TEM) in the treatment of rare rectal condition like mesenchymal tumors, condylomas, endometriosis and melanoma. METHODS We retrospectively reviewed a twenty-three years database. Fifty-two patients were enrolled in this study. The lesions were considered suitable for TEM if they were within 20 cm from the anus. All of them underwent an accurate preoperative workup consisting in clinical examination, total colonoscopy with biopsies, endoscopic ultrasonography, and pelvic computerized tomography or pelvic magnetic resonance imaging. Operative time, intraoperative complications, rate of conversion, tumor size, postoperative morbidity, mortality, the length of hospital stay, local and distant recurrence were analyzed. RESULTS Among the 1328 patients treated by TEM in our department, the 52 patients with rectal abnormalities other than adenoma or adenocarcinoma represented 4.4%. There were 30 males (57.7%) and 22 females (42.3%). Mean age was 55 years (median = 60, range = 24-78). This series included 14 (26.9%) gastrointestinal stromal tumors, 21 neuroendocrine tumors (40.4%), 1 ganglioneuroma (1.9%), 2 solitary ulcers in the rectum (3.8%), 6 cases of rectal endometriosis (11.5%), 6 cases of rectal condylomatosis (11.5%) and 2 rectal melanomas (3.8%). Mean lesion diameter was 2.7 cm (median: 4, range: 0.4-8). Mean distance from the anal verge was 9.5 cm (median: 10, range: 4-15). One patient operated for rectal melanoma developed distant metastases and died two years after the operation. We experienced 2 local recurrences (3.8%) with an overall survival equal to 97.6% (95%CI: 95%-99%) at the end of follow-up and a disease free survival of 98% (95%CI: 96%-99%). CONCLUSION We could conclude that TEM is an important therapeutical option for rectal rare conditions. PMID:27668073

  6. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

    PubMed Central

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-01-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients. PMID:18506179

  7. Functional role of the Ca{sup 2+}-activated Cl{sup −} channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

    SciTech Connect

    Berglund, Erik; Akcakaya, Pinar; Berglund, David; Karlsson, Fredrik; Vukojević, Vladana; Lee, Linkiat; Bogdanović, Darko; Lui, Weng-Onn; Larsson, Catharina; Zedenius, Jan; Fröbom, Robin; Bränström, Robert

    2014-08-15

    DOG1, a Ca{sup 2+}-activated Cl{sup −} channel (CaCC), was identified in 2004 to be robustly expressed in gastrointestinal stromal tumors (GIST). It was rapidly included as a tumor marker in routine diagnostics, but the functional role remained unknown. CaCCs are important regulators of normal physiological functions, but also implicated in tumorigenesis, cancer progression, metastasis, cell migration, apoptosis, proliferation and viability in several malignancies. We therefore investigated whether DOG1 plays a role in the three latter in GIST by utilizing in vitro cell model systems. Confocal microscopy identified different subcellular localizations of DOG1 in imatinib-sensitive and imatinib-resistant cells. Electrophysiological studies confirmed that DOG1-specific pharmacological agents possess potent activating and inhibiting properties. Proliferation assays showed small effects up to 72 h, and flow cytometric analysis of adherent cells with 7-AAD/Annexin V detected no pharmacological effects on viable GIST cells. However, inhibition of DOG1 conveyed pro-apoptotic effects among early apoptotic imatinib-resistant cells. In conclusion, DOG1 generates Cl{sup −} currents in GIST that can be regulated pharmacologically, with small effects on cell viability and proliferation in vitro. Inhibition of DOG1 might act pro-apoptotic on some early apoptotic GIST cell populations. Further studies are warranted to fully illuminate the function of DOG1 and its potential as therapeutic target. - Highlights: • Subcellular DOG1 localization varies between GIST cells. • DOG1 in GIST is voltage- and Ca{sup 2+}-activated. • Known TMEM16A modulators, like A01 and Eact, modulate DOG1. • DOG1 has small effects on cell viability and proliferation in vitro. • DOG1 impact early apoptotic GIST cells to undergo late apoptosis.

  8. A Role for Adjuvant RFA in Managing Hepatic Metastases from Gastrointestinal Stromal Tumors (GIST) After Treatment with Targeted Systemic Therapy Using Kinase Inhibitors

    SciTech Connect

    Hakimé, Antoine Cesne, Axel Le Deschamps, Frederic Farouil, Geoffroy Boudabous, Sana Aupérin, Anne Domont, Julien Debaere, Thierry

    2013-04-16

    PurposeThis study was designed to assess the role of radiofrequency ablation (RFA) in the multimodality management of gastrointestinal stromal tumors (GIST) in patients undergoing targeted tyrosine kinase inhibitor therapy (TKI) for liver metastases.MethodsOutcomes of 17 patients who underwent liver RFA for 27 metastatic GIST after TKI therapy, from January 2004 to March 2012, were retrospectively analyzed. Mean maximum tumor diameter was 2.5 ± 1 cm (range 0.9–4.5 cm). In seven patients (group A), RFA of all residual tumors was performed, with curative intent, and TKI therapy was discontinued. In five patients (group B), RFA of all residual tumors was performed upon achieving the best morphological response with TKI therapy, which was maintained after RFA. In another five patients (group C), RFA was performed on individual liver metastases which were progressive under TKI therapy.ResultsAll 27 targeted tumors were completely ablated, without local recurrence during the mean follow-up period of 49 months. No major complications occurred. Two minor complications were reported (11 %). Only two patients (both in group C) died at 20 and 48 months. Two-year progression-free survival (PFS) after RFA was 29 % in group A, 75 % in group B, and 20 % in group C.ConclusionsRFA in patients, previously treated with TKI, is feasible and safe. Our data suggest that RFA is a useful therapeutic option in patients with metastatic GIST and should be performed at the time of best clinical response with patient maintained under TKI after the procedure.

  9. The Therapeutic Response of Gastrointestinal Stromal Tumors to Imatinib Treatment Assessed by Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Histopathological Correlation

    PubMed Central

    Zhang, Chunfang; Wang, He; Cheng, Jin; Wu, Weizhen; Hong, Nan; Wang, Yi

    2016-01-01

    Purpose To exploit the intravoxel incoherent motion (IVIM) diffusion-weighted (DW) MRI when evaluating the therapeutic response of gastrointestinal stromal tumors (GIST) to Imatinib in a mouse model. Materials and Methods Mice with xenografts bearing cells from the GIST-T1 cell line were randomly divided into a treated group receiving Imatinib and a control group. DWMRI scans with 14 b-values (0–1500 s/mm2) were performed before and after treatment (days 1, 3 and 7). IVIM related parameters perfusion fractions (fp) and perfusion-related diffusion coefficients (D*) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the DWMRI signal decay. The mean changes from baseline to each post-treatment time point for each measurement (ΔADC, Δfp and ΔD*) were calculated. The differences of mean changes between the two groups were tested for statistical significance. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. Results Increases in ADC of the treated group were higher than those of the control group after treatment, whereas statistical significances were not observed. Compared to the control group, D* in the treated group decreased significantly (ΔD*treated = -41%, -49%, and -49% with P = 0.0001, 0.0001 and 0.0001), and fp increased significantly (Δfptreated = 79%, 82% and 110%, with P = 0.001, 0.0001 and P = 0.0007) on days 1, 3 and 7 after treatment. Histopathological analyses demonstrated different tumor tissue characteristics between the treated and control groups. Conclusion IVIM measurements may serve as more sensitive imaging biomarkers than ADC when assessing GIST response to Imatinib as early as one day after treatment. PMID:27911930

  10. Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor

    PubMed Central

    Komatsu, Yoshito; Ohki, Emiko; Ueno, Naomi; Yoshida, Ai; Toyoshima, Yasuharu; Ueda, Eiji; Houzawa, Hiroyuki; Togo, Kanae; Nishida, Toshirou

    2015-01-01

    Objective This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers. Methods Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day. Results No unexpected safety issues occurred. Grade ≥ 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16–24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7–24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88–94). Higher relative dose intensity (≥70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. ≥1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand–foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456–0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492–0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival. Conclusion Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events. PMID:26373318

  11. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-03

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  12. Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotype-phenotype correlation and validation of a high-resolution melting assay for mutational testing.

    PubMed

    Künstlinger, Helen; Huss, Sebastian; Merkelbach-Bruse, Sabine; Binot, Elke; Kleine, Michaela Angelika; Loeser, Heike; Mittler, Jens; Hartmann, Wolfgang; Hohenberger, Peter; Reichardt, Peter; Büttner, Reinhard; Wardelmann, Eva; Schildhaus, Hans-Ulrich

    2013-11-01

    KIT exon 9 mutations in gastrointestinal stromal tumors (GISTs) are highly relevant and have direct therapeutic implications. In this context, we established and validated a fast and sensitive high-resolution melting assay. Analyzing 126 primary and 18 metastatic KIT exon 9-mutated cases from our registry, we demonstrate that the mutational spectrum of exon 9 is broader than previously thought and describe 3 novel mutations. Including these cases and the common p.A502_Y503dup mutation, we provide a comprehensive list of all known KIT exon 9 mutations according to the Human Genome Variation Society nomenclature. Two of the newly described mutations were associated with an aggressive phenotype and tumor progression while being treated with 400 mg imatinib, indicating that also GIST with rare exon 9 mutations could be treated with increased imatinib dosage. On the basis of >1500 GISTs from our registry, we have determined the frequency of KIT exon 9 mutations to be 9.2% among all GISTs and 22.5% among small-bowel cases. We describe for the first time that nearly 20% of exon 9-mutated GIST occur in the stomach or rectum. Furthermore, we provide first evidence that exon 9-mutated GISTs metastasize significantly more often to the peritoneum than to the liver. Performing extensive statistical analyses on data from our registry and from the literature, we demonstrate that KIT exon 9 mutations are neither associated with intermediate-risk/high-risk status nor overrepresented among metastatic lesions. Thus, we conclude that exon 9 mutations per se do not have prognostic relevance.

  13. miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours.

    PubMed

    Ihle, Michaela Angelika; Trautmann, Marcel; Kuenstlinger, Helen; Huss, Sebastian; Heydt, Carina; Fassunke, Jana; Wardelmann, Eva; Bauer, Sebastian; Schildhaus, Hans-Ulrich; Buettner, Reinhard; Merkelbach-Bruse, Sabine

    2015-08-01

    Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In gastrointestinal stromal tumours (GISTs) expression of miR-221 and miR-222 is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-221 and miR-222 expression profiles in different GIST subtypes and the functional role of these miRNAs. Expression of miR-221 and miR-222 was analysed in six KIT exon 9 and three KIT exon 11 mutated and nine wildtype GISTs by qPCR. Viability and apoptosis were examined in three different, KIT positive GIST cell lines (GIST882, GIST-T1 and GIST48) after overexpression of these miRNAs. The modulation of KIT and the PI3K/AKT pathways was determined by Western blot. Wildtype and KIT mutated GISTs revealed reduced miRNA expression compared to adequate control tissue. miRNA expression was lower for wildtype compared to mutated GISTs. Transient transfection of miR-221 and miR-222 reduced viability and induced apoptosis by inhibition of KIT expression and its phosphorylation and activation of caspases 3 and 7 in all three GIST cell lines. p-AKT, AKT and BCL2 expression was reduced after miRNA transfection whereas only slight influence on p-MTOR, MTOR and BCL2L11 (BIM) was detected. Our results demonstrate that miR-221 and miR-222 which are downregulated in wildtype and mutated GISTs, induce apoptosis in vitro by a signalling cascade involving KIT, AKT and BCL2. Therefore, overexpression of these miRNAs seems to functionally counteract oncogenic signalling pathways in GIST.

  14. Surgical Management of Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Pediatric and Wildtype GIST Clinic.

    PubMed

    Weldon, Christopher B; Madenci, Arin L; Boikos, Sosipatros A; Janeway, Katherine A; George, Suzanne; von Mehren, Margaret; Pappo, Alberto S; Schiffman, Joshua D; Wright, Jennifer; Trent, Jonathan C; Pacak, Karel; Stratakis, Constantine A; Helman, Lee J; La Quaglia, Michael P

    2016-12-28

    Purpose Wild-type gastrointestinal stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that predominantly affects children. We sought to determine the effect on event-free survival (EFS) of staging variables, extent of resection, and repeat resection of tumors. Methods In 2008, a WT-GIST clinic was established at the National Cancer Institute, allowing the development of a large clinical database. We included participants who underwent resection of WT-GIST. Associations with EFS (ie, freedom from disease progression or recurrence) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. Results Among 76 participants with WT-GISTs, the median follow-up was 4.1 years. Overall EFS (± SE) was 72.6 ± 5.4% at 1 year, 57.6 ± 6.2% at 2 years, 23.7 ± 6.0% at 5 years, and 16.3 ± 5.5% at 10 years postoperatively. Hazard of disease progression or recurrence was significantly increased for patients with metastatic disease (adjusted hazard ratio [AHR], 2.3; 95% CI, 1.0 to 5.1; P = .04) and > 5 mitoses per 50 high-power fields (AHR, 2.5; 95% CI, 1.1 to 6.0; P = .03), whereas there was no significant effect of negative microscopic resection margins (AHR, 0.9; 95% CI, 0.4 to 2.2; P = 0.86). There was no association between type of gastric resection (ie, anatomic v partial/wedge) and EFS ( P = .67). Repeated resection after the initial resection was significantly associated with decreasing postoperative EFS ( P < .01). Five patients (6%) died after initial enrollment in 2008. Conclusion WT-GIST is an indolent disease, and most patients survive with disease progression. We found no improvement in EFS with more extensive or serial resections. Disease progression or recurrence may be more closely related to tumor biology than surgical management. These data suggest that resections for WT-GISTs be restricted to the initial procedure and that subsequent resections be performed only to address symptoms such as

  15. Short- and Long-Term Outcomes of Laparoscopic Versus Open Resection for Gastric Gastrointestinal Stromal Tumors: A Propensity Score-Matching Analysis.

    PubMed

    Chen, Qing-Feng; Huang, Chang-Ming; Lin, Mi; Lin, Jian-Xian; Lu, Jun; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Chen, Qi-Yue; Cao, Long-Long; Tu, Ru-Hong

    2016-04-01

    Published reports on laparoscopic resection of gastric gastrointestinal stromal tumor (GIST) were limited to small experiences and selection bias. Two hundred fourteen patients who underwent primary gastric GIST resection at our institution (January 2006-December 2012) were identified from a prospectively collected database. Laparoscopic resections (LAP) were performed in 133 patients, and open resections (OPEN) were performed in 81 patients. The short- and long-term outcomes were analyzed using propensity-score matching (PSM) by comparing the clinicopathological factors between these groups. The tumor resection method and tumor size were significantly different between the LAP and OPEN groups. After PSM, there were no differences (P > 0.05) in these clinicopathological factors. The LAP group had less blood loss and shorter operation time, time to first flatus, time to first fluid diet, time to gastric tube removal, and postoperative stay before PSM. In addition, there were no differences regarding the time of drainage tube removal or hospitalization expense. Other than the time of gastric tube removal, which was similar in these 2 groups, the short-term outcomes were similar before and after PSM. The rates of postoperative complications in the LAP and OPEN groups were 6.8% and 22.8%, respectively, before PSM (P = 0.001) and 5.6% and 22.5%, respectively, after PSM (P = 0.004). The multivariate analyses for complications showed that tumors were located in the middle of the stomach, and the operation method and proximal gastrectomy were independent risk factors before and after PSM. The 5-year cumulative survival rates in the LAP and OPEN groups were 95.4% and 85.9%, respectively, (P = 0.07) before PSM and 93.1% and 91.9%, respectively, (P = 0.69) after PSM (not significantly different). Laparoscopic resection for gastric GISTs had better short-term outcomes and similar long-term outcomes compared with open surgery. Localized gastric GISTs can be

  16. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation.

    PubMed

    Kajimoto, Noriko; Nakai, Norihiro; Ohkouchi, Mizuka; Hashikura, Yuka; Liu-Kimura, Ning-Ning; Isozaki, Koji; Hirota, Seiichi

    2015-01-01

    Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology.

  17. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients

    PubMed Central

    2012-01-01

    Abstract Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only in non progressive patients. Background Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown. Methods A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed. Results There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32%) and small bowel (29%). Sites of metastases were mainly liver (82%) and peritoneum (79%). The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553). Median haemoglobin (Hb) level prior to EPO was 9 g/dL (range 6,9-11,8) and 11,7 g/dL (range 6,8-14,4) after 2 months. An increase of more than 2 g/dL was observed in 18 (53%) of patients. None of the 7 patients who progressed (PD) under imatinib treatment (400 mg/day) experienced HB response, as compared to 66% (18/27) of the remaining patients (PR + SD) (p = 0,002). Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day) vs 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response. Conclusion EPO enables to

  18. Rectal neuroendocrine neoplasms: a case report

    PubMed Central

    Su, Hao

    2016-01-01

    The gastrointestinal neuroendocrine neoplasms (GI-NENs) are very rare, among which second most common type is the rectal NENs in China. Patients with rectal NENs may experience non-specific symptoms such as pain, perianal bulge, anemia, and bloody stools, and surgery is considered as the first treatment for rectal NENs. We report a case of rectal NENs in a 68-year-old male patient with bloody stools, who received surgery and postoperative pathology revealed an elevated well-differentiated neuroendocrine carcinoma. PMID:28138616

  19. Rectal Dose-Volume Histogram Parameters Are Associated With Long-Term Patient-Reported Gastrointestinal Quality of Life After Conventional and High-Dose Radiation for Prostate Cancer: A Subgroup Analysis of a Randomized Trial

    SciTech Connect

    Nguyen, Paul L.; Chen, Ronald C.; Hoffman, Karen E.; Trofimov, Alexei; Efstathiou, Jason A.; Coen, John J.; Shipley, William U.; Zietman, Anthony L.; Talcott, James A.

    2010-11-15

    Purpose: We examined whether rectal dose-volume histogram (DVH) parameters were associated with long-term patient-reported gastrointestinal (GI) quality of life (QOL) after conventional (70.2 GyE) or high-dose (79.2 GyE) radiation for prostate cancer. Methods and Materials: Of 64 men with localized prostate cancer alive with a minimum 7-year follow-up after treatment as part of a randomized trial with either 70.2 GyE or 79.2 GyE of external beam radiation at Massachusetts General Hospital, 56 men (88%) returned a QOL questionnaire, and 50 of those men had DVH information. The DVH parameters of the anterior rectal wall were correlated with patient-reported long-term GI QOL using Pearson correlation and t tests. Results: There was a trend toward an association between increased long-term GI dysfunction and higher V60 (p = 0.07), V65 (p = 0.06), V70 (p = 0.09), and V75 (p = 0.09). When dichotomized by their medians, a V60 > 54% (p = 0.04), V70 > 44% (p = 0.06), and V75 > 39% (p = 0.06) were associated with increased long-term GI dysfunction. There was no difference in long-term GI dysfunction between men on the conventional vs. high-dose arms (p = 0.49). Conclusions: Dose-volume histogram parameters of the anterior rectal wall were associated with long-term patient-reported GI QOL after prostate radiation, whereas the dose prescribed to the prostate was not, suggesting that DVH constraints, rather than total prescribed dose, may have the greatest impact on long-term bowel dysfunction, and therefore that continued dose escalation may be feasible if appropriate dose-volume constraints are met.

  20. A rare cause of chronic rectal bleeding in children; solitary rectal ulcer: case report.

    PubMed

    Temiz, Abdulkerim; Tander, Burak; Temiz, Muhyittin; Barış, Sancar; Arıtürk, Ender

    2011-03-01

    Solitary rectal ulcer causing lower gastrointestinal bleeding is extremely rare in children. Rare presentation, non-specific symptoms, insufficient experience, and characteristics mimicking other rectal diseases may cause misdiagnosis or delay of diagnosis in some pediatric patients. Here, we report a 10-year-old boy with solitary rectal ulcer diagnosed two years after onset of the symptoms who responded well to the conservative therapy, including high-fiber diet, laxatives, defecation training, and sucralfate enema.

  1. What Are Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... the GI tract, called the interstitial cells of Cajal (ICCs). ICCs are cells of the autonomic nervous system, the part of the nervous system that regulates body processes such as digesting food. ICCs are sometimes ...

  2. Effects of gastrointestinal parasites on parasite burden, rectal temperature, and antibody titer responses to vaccination and infectious bovine rhinotracheitis virus challenge.

    PubMed

    Schutz, J S; Carroll, J A; Gasbarre, L C; Shelton, T A; Nordstrom, S T; Hutcheson, J P; Van Campen, H; Engle, T E

    2012-06-01

    Thirty-three colostrum-deprived Holstein bull calves (initial BW of 131 ± 4 kg) were used to determine the effect of timing of anthelmintic administration relative to vaccination on antibody titer response to vaccine component antigens. When calves were at least 3 mo of age, they were sorted randomly into individual pens and assigned to 1 of 3 treatment groups, treatments consisted of 1) dewormed 2 wk before vaccination (DPV), 2) dewormed at the time of vaccination (DV), or 3) control, vaccinated but not dewormed (CONT). All calves were inoculated with infective larvae of brown stomach worms (Ostertagia ostertagi) and intestinal worms (Cooperia spp.) on d 1, 7, 10, 14, and 18 for a total dose of 235,710 infective larvae per calf. Calves (DPV and DV) were dewormed on d 21 or 35 with a 10% fenbendazole suspension at 5 mg/kg of BW. On d 35, all calves were vaccinated with a modified-live virus respiratory vaccine containing IBRV (infectious bovine rhinotracheitis virus), BVDV-1 (bovine viral diarrhea virus genotype 1), BVDV-2 (BVDV genotype 2), PI-3 (parainfluenza-3), and BRSV (bovine respiratory syncytial virus). During the 103-d experiment, weekly fecal egg counts, blood, and rectal temperatures were collected and health status was recorded daily. Blood samples were obtained weekly to determine serum neutralizing (SN) antibody titers to IBRV, BVDV-1, BVDV-2, and PI-3 and cytokine levels for IL-4, IL-6, TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-gamma). There was a tendency (P < 0.09) for CONT calves to have greater IL-4 concentrations. By design, control calves had greater (P < 0.01) fecal egg counts during the experiment. All calves developed antibody titers to IBRV, BVDV-1, BVDV-2, and PI-3 by d 15 postvaccination. On d 88, all calves were challenged with IBRV and blood samples were obtained on d 88, 89, 90, 93, 95, 98, 99, and 103. All calves had increased rectal temperatures during the final 7 d of the IBRV challenge. However, the CONT group had

  3. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2016-03-28

    Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

  4. Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors. An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors

    PubMed Central

    Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy P.; Miettinen, Markku M.

    2016-01-01

    The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors. PMID:27419370

  5. Targeted ultra-deep sequencing unveils a lack of driver-gene mutations linking non-hereditary gastrointestinal stromal tumors and highly prevalent second primary malignancies: random or nonrandom, that is the question

    PubMed Central

    Kuo, Yung-Chia; Hsu, Hung-Chih; Chen, Jen-Shi; Chen, Tse-Ching; Wu, Ren-Chin; Chiu, Cheng-Tang; Yeh, Chun-Nan; Yeh, Ta-Sen

    2016-01-01

    The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction. PMID:27806309

  6. Ovarian mucinous epithelial neoplasm showing immunohistochemical pattern of lower gastrointestinal origin with stromal minor sex-cord elements: A case report.

    PubMed

    Ueda, Taeko; Nakagawa, Hitomi; Hachisuga, Toru

    2014-12-01

    •We report a case of an ovarian mucinous cystadenoma that exhibited extensive sex-cord differentiation.•The ovarian tumor coincided with a uterine endometrial carcinoma.•The immunohistochemical pattern of mucinous epithelium of the ovarian tumor was suggestive of lower gastrointestinal origin.

  7. Microfluidic deletion/insertion analysis for rapid screening of KIT and PDGFRA mutations in CD117-positive gastrointestinal stromal tumors: diagnostic applications and report of a new KIT mutation.

    PubMed

    Zamò, Alberto; Bertolaso, Anna; Franceschetti, Ilaria; Weirich, Gregor; Capelli, Paola; Pecori, Sara; Chilosi, Marco; Hoefler, Heinz; Menestrina, Fabio; Scarpa, Aldo

    2007-04-01

    Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions >or=3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.

  8. Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial

    ClinicalTrials.gov

    2017-03-08

    Adenocarcinoma; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

  9. Gastrointestinal stromal tumors - quantitative detection of the Ki-67, TPX2, TOP2A, and hTERT telomerase subunit mRNA levels to determine proliferation activity and a potential for aggressive biological behavior.

    PubMed

    Kalfusova, A; Hilska, I; Krskova, L; Kalinova, M; Linke, Z; Kodet, R

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) have an unpredictable biological potential ranging from benign to malignant. Molecular markers involved in the mechanisms of proliferation and cellular senescence may provide additional information about biological behavior of the tumor. The aim of the present study was to investigate Ki-67, TPX2, TOP2A and hTERT mRNA expression levels in specimens from patients with GISTs to define relationships between proliferation activity and biological potential and progression of the disease. We measured Ki-67, TPX2, TOP2A and hTERT mRNA levels using quantitative real-time reverse transcription PCR (RQ RT PCR). The highest Ki-67, TPX2, TOP2A and hTERT mRNA expression levels were found in the highly proliferative BLs (18 specimens), in comparison with GISTs (137 specimens) and LMSs (9 specimens). Patients with GISTs and adequate information about mitotic activity, tumor size and anatomical site (84 specimens) were divided into two groups - GISTs with benign (29 patients) and with malignant (55 patients) potential. We observed association between higher Ki-67, TPX2 and hTERT mRNA levels and the GISTs with malignant potential. Univariate analysis (57 patients with available follow-up information) of survival (Kaplan Meier curves method) revealed a correlation between higher levels of TPX2, Ki-67 and hTERT markers and shorter event-free survival (EFS) or poorer overall survival (OS). The results demonstrate the importance of quantitative assessment of the proliferation activity in GISTs. Proliferation markers of Ki-67, TPX2, TOP2A and hTERT are suitable markers for detection the proliferation activity and telomerase activity of these tumors. Furthermore, the assessment of TPX2, Ki-67 and hTERT expression levels is appropriate for determination of malignant potential of GISTs.

  10. Transanal Endoscopic Operation for Benign Rectal Lesions and T1 Carcinoma

    PubMed Central

    Yoshihara, Emi; Dedrye, Lieven; Vindevoghel, Koen; Nuytens, Frederiek; Pottel, Hans

    2017-01-01

    Background and Objectives: Transanal endoscopic operation (TEO) is a minimally invasive technique used for local excision of benign and selected malignant rectal lesions. The purpose of this study was to investigate the feasibility, safety, and oncological outcomes of the procedure and to report the experience in 3 centers. Methods: Retrospective review of a prospectively collected database was performed of all patients with benign lesions or ≤cT1N0 rectal cancer who underwent TEO with curative intent at 3 Belgian centers (2012 through 2014). Results: Eighty-three patients underwent 84 TEOs for 89 rectal lesions (37 adenomas, 43 adenocarcinomas, 1 gastrointestinal stromal tumor, 1 lipoma, 2 neuroendocrine tumors, and 5 scar tissues). Operative time was associated with lesion size (P < .001). Postoperative complications occurred in 13 patients: 7 hemorrhages, 1 urinary tract infection, 1 urinary retention, 2 abscesses, 1 anastomotic stenosis, and 1 entrance into the peritoneal cavity. Median hospital stay was 3 days (range, 1–8). During a median follow-up of 13 months (range, 2–27), there was 1 recurrence. Conclusion: Although longer follow-up is still necessary, TEO appears to be an effective method of excising benign tumors and low-risk T1 carcinomas of the rectum. However, TEO should be considered as part of the diagnostic work-up. Furthermore, the resected specimen of a TEO procedure allows adequate local staging in contrast to an endoscopic piecemeal excision. Nevertheless, definitive histology must be appreciated, and in case of unfavorable histology, radical salvage resection still has to be performed. PMID:28144126

  11. Gastrointestinal complications of von Recklinghausen's disease: two case reports and a review of the literature.

    PubMed

    Pinsk, I; Dukhno, O; Ovnat, A; Levy, I

    2003-12-01

    There are few reports of the association between neurofibromatosis (von Recklinghausen's disease) and large, solid stromal tumours of the gastrointestinal tract. The prevalence of gastrointestinal involvement in von Recklinghausen's disease has been estimated at 11%-25%. Some associated gastrointestinal stromal tumours present clinically as bowel obstruction, perforation or gastrointestinal bleeding. We recently treated two patients with this condition who presented with gastrointestinal bleeding and were diagnosed with gastrointestinal stromal tumours. We report the unique aspects of these cases and discuss the diagnostic and management problems that are posed by this unusual association.

  12. Digital rectal exam

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007069.htm Digital rectal exam To use the sharing features on this page, please enable JavaScript. A digital rectal exam is an examination of the lower ...

  13. Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  14. Rectal ulcer with an elusive diagnosis: all that ulcers is not Crohn disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A single rectal ulcer is an uncommon finding in children with gastrointestinal disease. Although inflammatory bowel disease (IBD) is foremost among the differential diagnoses, a primary immunological defect should not be forgotten. Because of the paucity of literature on the association of rectal ul...

  15. Genetics Home Reference: gastrointestinal stromal tumor

    MedlinePlus

    ... membrane of certain cell types and stimulate signaling pathways inside the cell. Receptor proteins have specific sites ... of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, ...

  16. How Are Gastrointestinal Stromal Tumors Diagnosed?

    MedlinePlus

    ... is injected into the blood. The amount of radioactivity used is very low. Because cancer cells in ... special camera creates a picture of areas of radioactivity in your body. PET scan images are not ...

  17. How Are Gastrointestinal Stromal Tumors Staged?

    MedlinePlus

    ... The cancer has spread to nearby lymph nodes. M categories for GIST M0: The cancer has not ... lungs). Stage grouping Once the T, N, and M categories have been determined, this information is combined, ...

  18. Gastric stromal tumor.

    PubMed

    Ovali, Gülgün Yilmaz; Tarhan, Serdar; Serter, Selim; Pabuşçu, Yüksel

    2005-06-01

    Gastric stromal tumors are rare neoplasms of the stomach. In this report we present a gastric stromal tumor with an exophytic growth pattern, and describe magnetic resonance imaging and endoscopic ultrasonography findings.

  19. Rectal Blue Nevus: Distinguishing Features of a Rare Entity

    PubMed Central

    Mohan, Neena; McCue, Peter; Quirk, Daniel

    2016-01-01

    A 26-year-old African American man with a history of depression and tuberculosis presented to the gastroenterology department after several months of rectal pain with bowel movements. Colonoscopy revealed hyperpigmentation in the distal rectum and internal hemorrhoids, which resulted in a diagnosis of blue nevi. This is only the third known description of a blue nevus involving the gastrointestinal mucosa. PMID:28008401

  20. Rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction: case report.

    PubMed

    Özçelik, Ümit; Bircan, Hüseyin Yüce; Eren, Eryiğit; Demiralay, Ebru; Işıklar, İclal; Demirağ, Alp; Moray, Gökhan

    2015-01-01

    Although diverticular disease of the colon is common, the occurrence of rectal diverticula is extremely rare with only sporadic reports in the literature since 1911. Symptomatic rectal diverticula are seen even less frequently, and surgical intervention is needed for only complicated cases. Here we report the case of a 63-year-old woman presenting with rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction.

  1. Rectal culture (image)

    MedlinePlus

    A rectal culture test is performed by inserting a cotton swab in the rectum. The swab is rotated gently, and withdrawn. A smear of the swab is placed in culture media to encourage the growth of microorganisms. The ...

  2. Rectal imaging and cancer.

    PubMed

    Vining, D J

    1998-09-01

    Rectal imaging has evolved substantially during the past 25 years and now offers surgeons exquisite anatomic detail and physiologic information. Dynamic cystoproctography, helical computed tomography, endoscopic ultrasonography, endorectal magnetic resonance imaging, and immunoscintigraphy have become standards for the diagnosis of rectal disease, staging of neoplasia, and survey of therapeutic results. The indications, limitations, and relative costs of current imaging methods are reviewed, and advances in imaging technology that promise future benefits to colorectal surgeons are introduced.

  3. Microstructure imaging of human rectal mucosa using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Liu, N. R.; Chen, G.; Chen, J. X.; Yan, J.; Zhuo, S. M.; Zheng, L. Q.; Jiang, X. S.

    2011-01-01

    Multiphoton microscopy (MPM) has high resolution and sensitivity. In this study, MPM was used to image microstructure of human rectal mucosa. The morphology and distribution of the main components in mucosa layer, absorptive cells and goblet cells in the epithelium, abundant intestinal glands in the lamina propria and smooth muscle fibers in the muscularis mucosa were clearly monitored. The variations of these components were tightly relevant to the pathology in gastrointestine system, especially early rectal cancer. The obtained images will be helpful for the diagnosis of early colorectal cancer.

  4. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer

    PubMed Central

    Santhanam, Srikanth; Alvarado, David M.; Ciorba, Matthew A.

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant side effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapies are a promising new approach to harness the body’s own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway is a particularly promising target for immunotherapy. Indoleamine 2,3 dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and kynurenine pathway metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth and luminal microbiota. This pathway’s role in other gastrointestinal malignancies such as gastric, pancreatic, esophageal and gastrointestinal stromal tumors (GIST) is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal and colitis associated cancer. PMID:26297050

  5. [Extragastrointestinal stromal tumor (EGIST)--a case review].

    PubMed

    Kolarík, J; Drápela, J

    2012-04-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Due to the presence of thyrosine kinase receptors within the tumor tissue, GIST is thought to originate from gastrointestinal pacemaker cells, the intersticial cells of Cajal. Tumors with the same morphological and imunohistochemical characteristics detected outside the gastrointestinal tract, are called extragastrointestinal stromal tumors (EGIST). Biological characteristics of these tumors is uncertain and the malignancy rates are difficult to predict. Surgical R0 resection in resecable tumors is the only option with the potential for complete cure. Nevertheless, the recurrence rates are high. Adjuvant biological treatment with imatinib, a thyrosine kinase inhibitor, reduces the risk of relapses. Imatinib administration is also the principal treatment method in metastatic GIST disorders. The article offers a short and complex overview of gastrointestinal stromal tumor (GIST) problematics and presents a case report of a patient suffering from EGIST of mesocolon transversum treated by R0 resection which was performed under multidisciplinary cooperation, with a specialist follow up.

  6. Rectal absorption of propylthiouracil.

    PubMed

    Bartle, W R; Walker, S E; Silverberg, J D

    1988-06-01

    The rectal absorption of propylthiouracil (PTU) was studied and compared to oral absorption in normal volunteers. Plasma levels of PTU after administration of suppositories of PTU base and PTU diethanolamine were significantly lower compared to the oral route. Elevated plasma reverse T3 levels were demonstrated after each treatment, however, suggesting a desirable therapeutic effect at this dosage level for all preparations.

  7. Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

    ClinicalTrials.gov

    2017-03-02

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  8. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer.

    PubMed

    Santhanam, Srikanth; Alvarado, David M; Ciorba, Matthew A

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant adverse effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapy is a promising new approach to harness the body's own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway (KP) is a particularly promising target for immunotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and KP metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth, and luminal microbiota. This pathway's role in other gastrointestinal (GI) malignancies such as gastric, pancreatic, esophageal, and GI stromal tumors is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal, and colitis-associated cancer.

  9. A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction

    PubMed Central

    Martin, Rachel; Mathews, Winn; Scarcliff, Steven

    2016-01-01

    Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction. PMID:27672104

  10. Gastrointestinal manifestations.

    PubMed

    Tanowitz, H B; Simon, D; Weiss, L M; Noyer, C; Coyle, C; Wittner, M

    1996-11-01

    Gastrointestinal disease is a common problem in the setting of HIV-1 infection. As patients live longer and other opportunistic pathogens are suppressed, these problems are becoming even more important in the quality of life.

  11. Hereditary gastrointestinal cancer syndromes.

    PubMed

    Lynch, Henry T; Lynch, Jane F; Shaw, Trudy G

    2011-07-01

    The rapid growth of molecular genetics and its attendant germline mutation discoveries has enabled identification of persons who are at an inordinately high cancer risk and, therefore, ideal candidates for prevention. However, one must fully appreciate the extensive genotypic and phenotypic heterogeneity that exists in hereditary cancer. Once the causative germline mutation has been identified in a patient, high-risk members of the family can be similarly tested and identified and provided highly targeted surveillance and management opportunities. DNA testing can change the individual's presumed risk status and affect decision making by patients and their physicians regarding surveillance and management. Our purpose is to describe familial/hereditary cancers of the gastrointestinal tract, including familial Barrett's esophagus, hereditary diffuse gastric cancer, gastrointestinal stromal tumors, familial adenomatous polyposis and desmoid tumors, Lynch syndrome, small bowel cancer, and familial pancreatic cancer. We use our discussion of Lynch syndrome as a model for diagnostic and clinical translation strategies for all hereditary gastrointestinal tract cancers, which clearly can then be extended to cancer of all anatomic sites. Highly pertinent questions from the patient's perspective include the following: What kind of counseling will be provided to a patient with a Lynch syndrome mutation, and should that counseling be mandatory? Does the proband have the responsibility to inform relatives about the familial mutation, even if the relatives do not want to know whether they carry it? Is the patient is responsible for notifying family members that a parent or sibling has Lynch syndrome? Can notification be forced and, if so, under what circumstances? These questions point out the need for criteria regarding which family members to inform and how to inform them.

  12. Extragastrointestinal Stromal Tumour of The Abdominal Wall - A Case Report

    PubMed Central

    Kumar, A. Sathish Selva; Padmini, R; Veena, G; Murugesan, N

    2013-01-01

    Stromal tumours occurring in areas other than the GastroIntestinal Tract (GIT) are known as Extra GastroIntestinal Stromal Tumours (EGISTs). They usually arise in the mesentery, omentum or retroperitoneum, while EGISTs which occur in the abdominal wall are very rare. Both gastrointestinal stromal tumours (GISTs) and EGISTs are histologically and immunophenotypically similar. We are reporting a case of EGIST, which occurred in the anterior abdominal wall in a twenty five-year-old female patient. The tumour was present in the right loin and imaging studies suggested that it was a desmoid tumour. It was surgically excised by doing an abdominal wall mesh repair. The histological examinations revealed a tumour with spindle cell morphology, with <2 mitoses per 50 High Power Field (HPF) and no necrosis, with tumour free margins. Immunohistochemistry was strongly positive for CD117 and Smooth Muscle Actin (SMA), while it was negative for β-catenin and S100. The patient is well post operatively and is on close follow up. EGISTs should be considered in the differential diagnosis of mesenchymal tumours which occur in the abdominal wall, inspite of their rarity, as the high risk patients may need Imatinib chemotherapy. PMID:24551695

  13. [Gastrointestinal bleeding].

    PubMed

    Lanas, Ángel

    2015-09-01

    In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes.

  14. Mucoadhesion and the gastrointestinal tract.

    PubMed

    Varum, Felipe J O; McConnell, Emma L; Sousa, Joao J S; Veiga, Francisco; Basit, Abdul W

    2008-01-01

    The concept of mucoadhesion is one that has the potential to improve the highly variable residence times experienced by drugs and dosage forms at various sites in the gastrointestinal tract, and consequently, to reduce variability and improve efficacy. Intimate contact with the mucosa should enhance absorption or improve topical therapy. A variety of approaches have been investigated for mucoadhesion in the gastrointestinal tract, particularly for the stomach and small intestine. Despite interesting results in these sites, mucoadhesive approaches have not yet shown success in humans. The potential of the lower gut for these applications has been largely neglected, although the large intestine in particular may benefit, and the colon has several factors that suggest mucoadhesion could be successful there, including lower motility and the possibility of a lower mucus turnover and thicker mucus layer. In vitro studies on colonic mucoadhesion show promise, and rectal administration has shown some positive results in vivo. This review considers the background to mucoadhesion with respect to the physiological conditions of the gastrointestinal tract as well as the principles that underlie this concept. Mucoadhesive approaches to gastrointestinal drug delivery will be examined, with particular attention given to the lower gut.

  15. Multicompartmental Pharmacokinetic Model of Tenofovir Delivery to the Rectal Mucosa by an Enema

    PubMed Central

    Gao, Yajing; Katz, David F.

    2017-01-01

    Rectal enemas that contain prophylactic levels of anti-HIV microbicides such as tenofovir have emerged as a promising dosage form to prevent sexually transmitted HIV infections. The enema vehicle is promising due to its likely ability to deliver a large amount of drug along the length of the rectal canal. Computational models of microbicide drug delivery by enemas can help their design process by determining key factors governing drug transport and, more specifically, the time history and degree of protection. They can also inform interpretations of experimental pharmacokinetic measures such as drug concentrations in biopsies. The present work begins rectal microbicide PK modeling, for enema vehicles. Results here show that a paramount factor in drug transport is the time of enema retention; direct connectivity between enema fluid and the fluid within rectal crypts is also important. Computations of the percentage of stromal volume protected by a single enema dose indicate that even with only a minute of enema retention, protection of 100% can be achieved after around 14 minutes post dose. Concentrations in biopsies are dependent on biopsy thickness; and control and/or knowledge of thickness could improve accuracy and decrease variability in biopsy measurements. Results here provide evidence that enemas are a promising dosage form for rectal microbicide delivery, and offer insights into their rational design. PMID:28114388

  16. An Unusual Case of Rectal and Ileal Carcinoid Tumors

    PubMed Central

    Abdulsamad, Molham; Abbas, Naeem; Balar, Bhavna

    2016-01-01

    Carcinoid tumor is the most common neuroendocrine tumor affecting the gastrointestinal tract. The coexistence of multifocal carcinoid lesions is a well-established phenomenon. Although intubation of the terminal ileum is not routinely attempted during colonoscopy, it can occasionally reveal the presence of some incidental findings. We present a patient with known rectal carcinoid, who was found to have another carcinoid lesion in the terminal ileum during surveillance colonoscopy. The patient underwent right hemicolectomy, and no chemotherapy was required as the patient was found to have stage 1 carcinoid tumor. PMID:28203126

  17. Chemoradiation of rectal cancer.

    PubMed

    Arrazubi, V; Suárez, J; Novas, P; Pérez-Hoyos, M T; Vera, R; Martínez Del Prado, P

    2013-02-01

    The treatment of locally advanced rectal cancer is a challenge. Surgery, chemotherapy and radiotherapy comprise the multimodal therapy that is administered in most cases. Therefore, a multidisciplinary approach is required. Because this cancer has a high rate of local recurrence, efforts have been made to improve clinical outcomes while minimizing toxicity and maintaining quality of life. Thus, total mesorectal excision technique was developed as the standard surgery, and chemotherapy and radiotherapy have been established as neoadjuvant treatment. Both approaches reduce locoregional relapse. Two neoadjuvant treatments have emerged as standards of care: short-course radiotherapy and long-course chemoradiotherapy with fluoropyrimidines; however, long-course chemoradiotherapy might be more appropriate for low-lying neoplasias, bulky tumours or tumours with near-circumferential margins. If neoadjuvant treatment is not administered and locally advanced stage is demonstrated in surgical specimens, adjuvant chemoradiotherapy is recommended. The addition of chemotherapy to the treatment regimen confers a significant benefit. Adjuvant chemotherapy is widely accepted despite scarce evidence of its benefit. The optimal time for surgery after neoadjuvant therapy, the treatment of low-risk T3N0 neoplasms, the convenience of avoiding radiotherapy in some cases and tailoring treatment to pathological response have been recurrent subjects of debate that warrant more extensive research. Adding new drugs, changing the treatment sequence and selecting the treatment based on prognostic or predictive factors other than stage remain experimental.

  18. Age and cellular context influence rectal prolapse formation in mice with caecal wall colorectal cancer xenografts

    PubMed Central

    Tommelein, Joke; Gremonprez, Félix; Verset, Laurine; De Vlieghere, Elly; Wagemans, Glenn; Gespach, Christian; Boterberg, Tom; Demetter, Pieter; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-01-01

    In patients with rectal prolapse is the prevalence of colorectal cancer increased, suggesting that a colorectal tumor may induce rectal prolapse. Establishment of tumor xenografts in immunodeficient mice after orthotopic inoculations of human colorectal cancer cells into the caecal wall is a widely used approach for the study of human colorectal cancer progression and preclinical evaluation of therapeutics. Remarkably, 70% of young mice carrying a COLO320DM caecal tumor showed symptoms of intussusception of the large bowel associated with intestinal lumen obstruction and rectal prolapse. The quantity of the COLO320DM bioluminescent signal of the first three weeks post-inoculation predicts prolapse in young mice. Rectal prolapse was not observed in adult mice carrying a COLO320DM caecal tumor or young mice carrying a HT29 caecal tumor. In contrast to HT29 tumors, which showed local invasion and metastasis, COLO320DM tumors demonstrated a non-invasive tumor with pushing borders without presence of metastasis. In conclusion, rectal prolapse can be linked to a non-invasive, space-occupying COLO320DM tumor in the gastrointestinal tract of young immunodeficient mice. These data reveal a model that can clarify the association of patients showing rectal prolapse with colorectal cancer. PMID:27689329

  19. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  20. [Gastrointestinal bezoars].

    PubMed

    Espinoza González, Ricardo

    2016-08-01

    Gastrointestinal bezoars are a concretion of indigested material that can be found in the gastrointestinal tract of humans and some animals. This material forms an intraluminal mass, more commonly located in the stomach. During a large period of history animal bezoars were considered antidotes to poisons and diseases. We report a historical overview since bezoars stones were thought to have medicinal properties. This magic conception was introduced in South America by Spanish conquerors. In Chile, bezoars are commonly found in a camelid named guanaco (Lama guanicoe). People at Central Chile and the Patagonia believed that bezoar stones had magical properties and they were traded at very high prices. In Santiago, during the eighteenth century the Jesuit apothecary sold preparations of bezoar stones. The human bezoars may be formed by non-digestible material like cellulose (phytobezoar), hair (trichobezoar), conglomerations of medications or his vehicles (pharmacobezoar or medication bezoar), milk and mucus component (lactobezoar) or other varieties of substances. This condition may be asymptomatic or can produce abdominal pain, ulceration, gastrointestinal bleeding, gastric outlet obstruction, perforation and mechanical intestinal obstruction. We report their classification, diagnostic modalities and treatment.

  1. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    PubMed Central

    Vootla, Vamshidhar; Ahmed, Rafeeq; Niazi, Masooma; Balar, Bhavna; Nayudu, Suresh

    2016-01-01

    Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass) and a low-grade neuroendocrine neoplasm (carcinoid of rectum). The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa. PMID:27920648

  2. Local management of rectal neoplasia.

    PubMed

    Touzios, John; Ludwig, Kirk A

    2008-11-01

    The treatment of rectal neoplasia, whether benign or malignant, challenges the surgeon. The challenge in treating rectal cancer is selecting the proper approach for the appropriate patient. In a small number of rectal cancer patients local excision may be the best approach. In an attempt to achieve two goals-cure of disease with a low rate of local failure and maintenance of function and quality of life-multiple approaches can be utilized. The key to obtaining a good outcome for any one patient is balancing the competing factors that impact on these goals. Any effective treatment aimed at controlling rectal cancer in the pelvis must take into account the disease in the bowel wall itself and the disease, or potential disease, in the mesorectum. The major downside of local excision techniques is the potential of leaving untreated disease in the mesorectum. Local management techniques avoid the potential morbidity, mortality, and functional consequences of a major abdominal radical resection and are thus quite effective in achieving the maintenance of function and quality of life goal. The issue for the transanal techniques is how they fare in achieving the first goal-cure of the cancer while keeping local recurrence rates to an absolute minimum. Without removing both the rectum and the mesorectum there is no completely accurate way to determine whether a rectal cancer has moved outside the bowel wall, so any decision on local management of a rectal neoplasm is a calculated risk. For benign neoplasia, the challenge is removing the lesion without having to resort to a major abdominal procedure.

  3. Do We Know What Causes Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... gene is found in all cells of the body. It directs the cell to make a protein called KIT, which causes the cell to grow and divide. Usually the c-kit gene in interstitial cells of Cajal (ICCs) is inactive. It is only active if ...

  4. Treatment for Gastrointestinal Stromal Tumors (GISTs) Based on Tumor Spread

    MedlinePlus

    ... These treatments may include radiofrequency ablation (RFA; using electric currents to heat the tumor), or ethanol ablation ( ... Life Events College Relay For Life Donate a Car Ways to Give Memorial Giving Planned Giving Leadership ...

  5. [Medical treatment for gastrointestinal stromal tumor (GIST) in Japan].

    PubMed

    Sato, Atsushi; Hamada, Kazuyuki; Imataka, Hiromi

    2012-05-01

    To facilitate an optimal diagnosis and treatment of GIST in Japan, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee. Multidisciplinary treatment planning is needed(involving pathologists, radiologists, surgeons and medical oncologists)for patients with GIST. Medical treatment is usually selected for unresectable GIST, metastatic GIST at the initial examination, and recurrent GIST. Imatinib is strongly recommended for patients with KIT-positive GIST; the standard dose of imatinib mesylate(Glivec)is 400 mg/day. For patients with imatinib-resistant GIST, Sunitinib (Sutent)is now approved in Japan and is covered by medical insurance. However, high-dose imatinib(>400mg/day)has not yet been approved in Japan.

  6. Rare cases reports of gastrointestinal stromal tumour (GIST)

    PubMed Central

    AMENDOLARA, M.; RAMUSCELLO, S.; BROGGIATO, A.; ANDREOTTI, A.; STEVANATO, G.; BONFIGLIO, M.; BERNARDI, M.; PARINI, D.; GALEOTTI, F.; RIZZO, M.

    2014-01-01

    The GISTs are rare tumours but even rarer is the localization in some districts. We reported two GISTs of the duodenum, two of the omentum and peritoneum, one of the rectum and one of a Meckel’s diverticulum. These exceptional locations are confirmed by the relative difficult diagnosis, obtained in some cases only by the surgical treatment despite the CT and MR. The endoscopy is useful in hemorrhagic and duodenum forms, only for the diagnosis and for the control of blood loss. Surgical treatment in all cases was decisive without the need to make use of adjuvant therapy, with positive long-term results, which excluded the disappearance of relapses or secondary lesions. PMID:24979104

  7. Accomplishments in 2008 in the Management of Gastrointestinal Stromal Tumors

    PubMed Central

    Renouf, Daniel; Blay, Jean-Yves; Blanke, Charles

    2009-01-01

    SUMMARY Overview of the Disease ProcessIncidencePrognosisPredictive MarkersCurrent General Therapy Standards in North America and EuropeLocalized or Potentially Resectable DiseaseUnresectable or Metastatic DiseaseAccomplishments During the YearTherapySurgical Issues and Perioperative TherapyImatinibSunitinibNew DrugsBiomarkersBasic and Other Translational ScienceWhat Needs to Be DoneFuture DirectionsComments on ResearchObstacles to Progress PMID:20011569

  8. Percutaneous Transhepatic Embolization of Bleeding Rectal Varices Using A New Embolic And Sclerotic Mixture Augmented By Amplatzer Vascular Plug 2

    PubMed Central

    Abdel-Aal, Ahmed Kamel; Dawoud, Nabila; Moustafa, Amr Soliman; Hamed, Maysoon F; Saddekni, Souheil

    2016-01-01

    We report a case of 59-year-old female with non-alcoholic-steato-hepatitis (NASH) induced cirrhosis, who presented with hematochezia. The patient had a history of bleeding esophageal varices treated with endoscopic variceal ligation (EVL). Colonoscopy showed large rectal varices which were the source of her lower gastrointestinal bleeding (LGIB). Since endoscopic treatment for LGIB are limited, and because the patient had portal vein thrombosis which contraindicated transjugular intrahepatic portosystemic shunt (TIPS), we performed percutaneous transhepatic embolization of her rectal varices using a new mixture of embolic and sclerotic agents, followed by Amplatzer plug 2 (AVP 2). To our knowledge, the use of this new mixture with the AVP 2 in the rectal varices treatment has not been previously published in literature. Our case provides an alternative treatment modality that can be used for rectal varices treatment, when TIPS and endoscopic management fails or is contraindicated. PMID:27761198

  9. MALT lymphoma of the rectum, presenting with rectal prolapsus: a case report

    PubMed Central

    2010-01-01

    Up to now, there have been only a few reported cases of Mucosa-associated lymphoid tissue (MALT) lymphomas arising in the rectum. Its clinical presentation is indistinguishable from that of rectal carcinoma but the treatment is apparently different. Symptoms of primary lymphomas involving the rectum include; anorexia, weight loss, change in bowel habits, obstruction, and bleeding. These symptoms are not disease specific and can be seen in many other gastrointestinal disorders. Patients with polypoid masses may present with obstruction symptoms. In this rare case, a female patient admitted to the emergency service with prolapsus of a rectal mass. The optimal treatment of rectal MALT lymphoma is not well defined yet, given the rarity of the disease. Surgical resection of the localized lesion and following adjuvant chemotherapy has proved to be an effective treatment option. However, a close and long-lasting follow-up is important. PMID:20180989

  10. The Role of Thymic Stromal Lymphopoietin (TSLP) in Allergic Disorders

    PubMed Central

    Ziegler, Steven F.

    2010-01-01

    Summary The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergens contact first occurs at mucosal sites in exposed to the external environment such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. PMID:21109412

  11. 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

  12. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

    PubMed

    Chung, Heeteak; Polf, Jerimy; Badiyan, Shahed; Biagioli, Matthew; Fernandez, Daniel; Latifi, Kujtim; Wilder, Richard; Mehta, Minesh; Chuong, Michael

    2017-01-01

    The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

  13. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  14. [Surgical treatment of rectal cancer].

    PubMed

    Vergara-Fernández, O; Salinas-Aragón, L E; Camacho-Mauries, D; Medina-Franco, H

    2010-01-01

    Rectal affection accounts for 30% of colorectal cancer. The standard of treatment is surgical resection, which often is curative. For superior and middle-rectal involvement, low anterior resection (LAR) is the preferred procedure. For tumors involving the lower portion of the rectum, abdominoperineal resection (APR) or LAR are the options of treatment, depending on sphincter involvement. The main surgical objective is to achieve a R0 resection with an appropriated total mesorrectal excision, greater number of lymph nodes and negative distal and radial margins. These surgical parameters have been used as quality indicators and have prognostic implications in terms of overall and disease-free survival. Total mesorectal excision with preservation of hypogastric nerves has shown a reduction in rates of sexual and bladder dysfunction as well as lower local recurrence. At specialized centers such procedures are performed by minimal invasive surgery; however the number of meta-analysis is scarce.

  15. Permission to Collect Blood Over Time for Research

    ClinicalTrials.gov

    2016-07-06

    Pancreatic Cancer; Gastrointestinal Neoplasms; Colon Rectal Cancer Adenocarcinoma; Esophageal Cancer; Gall Bladder Cancer; Gastric (Stomach) Cancer; Gastrooesophageal Cancer; Gastrointestinal Stromal Tumor (GIST); Hepatobiliary Neoplasm; Liver Carcinoma; Gallbladder Carcinoma; Bile Duct Carcinoma; Carcinoma of the Large Intestine; Anal Cancer

  16. Magnamosis: a novel technique for the management of rectal atresia

    PubMed Central

    Russell, Katie W; Rollins, Michael D; Feola, G Peter; Scaife, Eric R

    2014-01-01

    We report a case of rectal atresia treated using magnets to create a rectal anastomosis. This minimally invasive technique is straightforward and effective for the treatment of rectal atresia in children. PMID:25096648

  17. Rare recurrence of a rare ovarian stromal tumor with luteinized cells: a case report

    PubMed Central

    2011-01-01

    Introduction Sex cord-stromal tumors of the ovary are uncommon. They behave unpredictably and often have a late recurrence, making counseling, management, and prediction of prognosis challenging. Case presentation A 52-year-old Moroccan woman with an sex cord-stromal tumors underwent a bilateral oophorectomy. The histology was unusual but was likely to be a luteinized thecoma with suspicious features for invasion. Seven years later, after a gastrointestinal bleed, a metastasis within the small bowel mucosa was detected. This represents probable isolated hematogenous or lymphatic spread, which is highly unusual, especially in the absence of concurrent peritoneal disease. Conclusions To the best of our knowledge, this is the second reported case of an sex cord-stromal tumors recurring in small bowel mucosa and mimicking a primary colorectal tumor. This highlights the diverse nature and behavior of these tumors. PMID:21816048

  18. Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2014-10-01

    The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

  19. Defining the distal margin of rectal cancer for surgical planning

    PubMed Central

    Kato, Takashi; Tanaka, Jun-Ichi

    2017-01-01

    Accurate measurement of the distal rectal tumor margin is essential in selecting the appropriate surgical procedure. However, there is no standard measurement method. The National Cancer Institute consensus group recommends use of the anal verge (AV) as a landmark, and the European Society of Gastrointestinal and Abdominal Radiology recommends use of the anorectal ring (ARR). In addition, whether measurements should be made on double contrast barium enema (BE) radiographs or magnetic resonance (MR) images remains controversial. We measured the distal tumor margin on both BE and MR images obtained preoperatively from 52 patients who underwent sphincter-saving resection for rectal cancer. The distances from the distal end of the tumor to the AV and the ARR were measured on both types of images, and the variability was investigated by Bland-Altman analysis. The mean distance from the tumor to the AV was 8.9 cm on the BE radiographs and 7.7 cm on the MR images (P=0.013). The mean distances to the ARR were 6.8 and 5.6 cm, respectively (P=0.070). Significant proportional bias was shown as the measured distances increased, the difference between the BE- and magnetic resonance imaging (MRI)-based measurements increased. Use of one or the other landmark did not affect selection of the appropriate surgical procedure. We conclude that an approximate 1-cm underestimation should be taken into account when MRI-based measurement of the distal rectal tumor margin is used to choose between sphincter-saving resection and abdominoperineal resection. PMID:28280625

  20. Mesenchymal stromal cell cryopreservation.

    PubMed

    Renzi, Sabrina; Lombardo, Tina; Dotti, Silvia; Dessì, Sara S; De Blasio, Pasquale; Ferrari, Maura

    2012-06-01

    The advent of stem cells and stem cell-based therapies for specific diseases requires particular knowledge of laboratory procedures, which not only guarantee the continuous production of cells, but also provide them an identity and integrity as close as possible to their origin. Their cryopreservation at temperatures below -80°C and typically below -140°C is of paramount importance. This target can be achieved by incorporating high molar concentrations of cryoprotectant mixtures that preserve cells from deleterious ice crystal formation. Usually, dimethyl sulfoxide (DMSO) and animal proteins are used as protectant reagents, but unexpected changes in stem cell fate and downstream toxicity effects have been reported, limiting their wide use in clinical settings. In scientific reviews, there are not much data regarding viability of mesenchymal stromal cells (MSCs) after the freezing/thawing process. During our routine analysis, a poor resistance to cryopreservation of these cells was observed, as well as their weak ability to replicate. This is an important point in the study of MSCs; moreover, it represents a limit for preservation and long-term storage. For this reason, MSCs isolated from equine, ovine, and rodent bone marrow and equine adipose tissue were compared using different cryopreservation solutions for this study of vitality. Our findings showed the best results regarding cell viability using a solution of fetal bovine serum with addition of 10% DMSO. In particular, we noted an increase in survival of equine bone marrow MSCs. This parameter has been evaluated by Trypan blue staining at fixed times (0, 24, and 48 hours post-thaw). This result highlights the fact that equine bone marrow MSCs are the frailest we analyzed. Therefore, it could be useful to delve further into this topic in order to improve the storage possibility for these cells and their potential use in cell-based therapies.

  1. Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Musio, Daniela; Izzo, Luciano; Pugliese, Federico; Izzo, Paolo; Bolognese, Antonio

    2013-01-01

    Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered. PMID:24392453

  2. Watch and wait approach to rectal cancer: A review.

    PubMed

    Pozo, Marcos E; Fang, Sandy H

    2015-11-27

    In 2014, there were an estimated 136800 new cases of colorectal cancer, making it the most common gastrointestinal malignancy. It is the second leading cause of cancer death in both men and women in the United States and over one-third of newly diagnosed patients have stage III (node-positive) disease. For stage II and III colorectal cancer patients, the mainstay of curative therapy is neoadjuvant therapy, followed by radical surgical resection of the rectum. However, the consequences of a proctectomy, either by low anterior resection or abdominoperineal resection, can lead to very extensive comorbidities, such as the need for a permanent colostomy, fecal incontinence, sexual and urinary dysfunction, and even mortality. Recently, trends of complete regression of the rectal cancer after neoadjuvant chemoradiation therapy have been confirmed by clinical and radiographic evaluation-this is known as complete clinical response (cCR). The "watch and wait" approach was first proposed by Dr. Angelita Habr-Gama in Brazil in 2009. Those patients with cCR are followed with close surveillance physical examinations, endoscopy, and imaging. Here, we review management of rectal cancer, the development of the "watch and wait" approach and its outcomes.

  3. Multiple rectal carcinoid tumors in monozygotic twins.

    PubMed

    Doi, Momoko; Ikawa, Osamu; Taniguchi, Hiroki; Kawamura, Takuji; Katsura, Kanade

    2016-08-01

    We report multiple rectal carcinoid tumors in monozygotic twins who, respectively, had 42 and 36 carcinoid tumors in the lower rectum. This is the first report about carcinoid tumors in monozygotic twins. Both twins developed a similar number of rectal carcinoids with a similar distribution. Investigation of their genetic background may provide information about the origin of these tumors.

  4. Fournier gangrene: rare complication of rectal cancer.

    PubMed

    Ossibi, Pierlesky Elion; Souiki, Tarik; Ibn Majdoub, Karim; Toughrai, Imane; Laalim, Said Ait; Mazaz, Khalid; Tenkorang, Somuah; Farih, My Hassan

    2015-01-01

    Fournier's Gangrene is a rare complication of rectal cancer. Its discovery is often delayed. It's incidence is about 0.3/100,000 populations in Western countries. We report a patient with peritoneal perforation of rectal cancer revealed by scrotal and perineal necrotizing fasciitis.

  5. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2015-10-24

    Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  6. Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women

    PubMed Central

    Cranston, Ross D.; Mayer, Kenneth H.; Febo, Irma; Duffill, Kathryn; Siegel, Aaron; Engstrom, Jarret C.; Nikiforov, Alexyi; Park, Seo-Young; Brand, Rhonda M.; Jacobson, Cindy; Giguere, Rebecca; Dolezal, Curtis; Frasca, Timothy; Leu, Cheng-Shiun; Schwartz, Jill L.; Carballo-Diéguez, Alex

    2016-01-01

    Objectives The purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM) and transgender women (TGW) at risk of HIV infection. Methods MSM and TGW aged 18–30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2) in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV) 1% gel. Results 248 participants were enrolled into Stage 1A. Participants’ average age was 23.3 years. The most common sexually transmitted infection (STIs) at baseline were Herpes simplex (HSV)-2 (16.1% by serology) and rectal Chlamydia trachomatis (CT) (10.1% by NAAT). 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs) were infections (N = 56) or gastrointestinal (N = 46) and were mild (69.6%) or moderate (28.0%). Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1) to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10) and of mild (87.2%) or moderate (10.3%) severity. Conclusions In this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population. Trial Registration ClinicalTrials.gov NCT01283360 PMID:27362788

  7. Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

    SciTech Connect

    Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella; McKibben, Brian T.; Henderson, Randal H.; Bryant, Curtis; Nichols, Romaine C.; Mendenhall, William M.; Li, Zuofeng; Su, Zhong; Morris, Christopher G.; Mendenhall, Nancy P.

    2015-01-01

    Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT, accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.

  8. Benign Post-Radiation Rectal Stricture Treated with Endoscopic Balloon Dilation and Intralesional Triamcinolone Injection

    PubMed Central

    Karanikas, Michael; Touzopoulos, Panagiotis; Mitrakas, Alexandros; Zezos, Petros; Zarogoulidis, Paul; Machairiotis, Nikolaos; Efremidou, Eleni; Liratzopoulos, Nikolaos; Polychronidis, Alexandros; Kouklakis, George

    2012-01-01

    Post-radiation stricture is a rare complication after pelvis irradiation, but must be in the mind of the clinician evaluating a lower gastrointestinal obstruction. Endoscopy has gained an important role in chronic radiation proctitis with several therapeutic options for management of intestinal strictures. The treatment of rectal strictures has been limited to surgery with high morbidity and mortality. Therefore, a less invasive therapeutic approach for benign rectal strictures, endoscopic balloon dilation with or without intralesional steroid injection, has become a common treatment modality. We present a case of benign post-radiation rectal stricture treated successfully with balloon dilation and adjuvant intralesional triamcinolone injection. A 70-year-old woman presented to the emergency room complaining for 2 weeks of diarrhea and meteorism, 11 years after radiation of the pelvis due to adenocarcinoma of the uterus. Colonoscopy revealed a stricture at the rectum and multiple endoscopic biopsies were obtained from the stricture. The stricture was treated with endoscopic balloon dilation and intralesional triamcinolone injection. The procedure appears to have a high success rate and a very low complication rate. Histologic examination of the biopsies revealed non-specific inflammatory changes of the rectal mucosa and no specific changes of the mucosa due to radiation. All biopsies were negative for malignancy. The patient is stricture-free 12 months post-treatment. PMID:23271987

  9. Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn.

    PubMed

    Freede, Margaret; Leasure, A Renee; Proskin, Howard M; Hatch, Daniel; Edwards, Karethy; Pascucci, MaryAnn; Smith, Patsy R

    2016-01-01

    This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.

  10. Gastrointestinal manifestations in cystic fibrosis.

    PubMed

    Eggermont, E

    1996-08-01

    CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.

  11. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

    PubMed Central

    Thomas, Andrew M.; Jesus, Eliane C.; Lopes, Ademar; Aguiar, Samuel; Begnami, Maria D.; Rocha, Rafael M.; Carpinetti, Paola Avelar; Camargo, Anamaria A.; Hoffmann, Christian; Freitas, Helano C.; Silva, Israel T.; Nunes, Diana N.; Setubal, João C.; Dias-Neto, Emmanuel

    2016-01-01

    droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer. PMID:28018861

  12. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling.

    PubMed

    Thomas, Andrew M; Jesus, Eliane C; Lopes, Ademar; Aguiar, Samuel; Begnami, Maria D; Rocha, Rafael M; Carpinetti, Paola Avelar; Camargo, Anamaria A; Hoffmann, Christian; Freitas, Helano C; Silva, Israel T; Nunes, Diana N; Setubal, João C; Dias-Neto, Emmanuel

    2016-01-01

    droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.

  13. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  14. Necrotizing cellulitis of the abdominal wall, caused by Pediococcus sp., due to rupture of a retroperitoneal stromal cell tumor

    PubMed Central

    Michalopoulos, Nick; Arampatzi, Stergiani; Papavramidis, Theodossis S.; Kotidis, Efstathios; Laskou, Styliani; Papavramidis, Spiros T.

    2013-01-01

    INTRODUCTION Soft tissue necrotizing infections are a significant cause of morbidity and mortality. The aim of this study is to present a patient with necrotizing infection of abdominal wall resulting from the rupture of a retroperitoneal stromal tumor. PRESENTATION OF CASE We present a 60-year-old Caucasian male patient with necrotizing infection of abdominal wall secondary to the rupture of a retroperitoneal stromal tumor. The patient was initially treated with debridement and fasciotomy of the anterior abdominal wall. Laparotomy revealed purulent peritonitis caused by infiltration and rupture of the splenic flexure by the tumor. Despite prompt intervention the patient died 19 days later. The isolated microorganism causing the infection was the rarely identified as cause of infections in humans Pediococcus sp., a gram-positive, catalase-negative coccus. DISCUSSION Necrotizing infections of abdominal wall are usually secondary either to perineal or to intra-abdominal infections. Gastrointestinal stromal cell tumors could be rarely complicated with perforation and abscess formation. In our case, the infiltrated by the extra-gastrointestinal stromal cell tumor ruptured colon was the source of the infection. The pediococci are rarely isolated as the cause of severe septicemia. CONCLUSION Ruptured retroperitoneal stromal cell tumors are extremely rare cause of necrotizing fasciitis, and before this case, Pediococcus sp. has never been isolated as the responsible agent. PMID:23357010

  15. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  16. Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2016-11-23

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  17. [Adjuvant chemotherapy of the colonic and rectal carcinoma: concepts and uptodate results].

    PubMed

    Weber, W; Nagel, G A

    1977-06-18

    The aim of adjuvant chemotherapy is the destruction of micrometastases after surgical removal of a malignant tumor. This treatment modality is gaining in importance in the light of experimental data and lcinical success in pediatric tumors. Results of ongoing studies in colo-rectal cancer show a marginal effect of prophylactic treatment with 5-fluorouracil. The treatment benefits in trials with historical controls are much greater than in studies with simultaneous controls. Use of historical controls is therefore of doubtful value. Ongoing trials use the combination of 5-fluorouracil and methyl-CCNU, which has been shown to double the remission rate in advanced gastrointestinal cancer. Adjuvant chemotherapy of colo-rectal cancer is still experimental and justified only in the framework of clinical trials.

  18. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-11-25

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; 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

  19. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

    PubMed

    Di Valentin, T; Asmis, T; Asselah, J; Aubin, F; Aucoin, N; Berry, S; Biagi, J; Booth, C M; Burkes, R; Coburn, N; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Frechette, D; Goel, R; Gray, S; Hammad, N; Jonker, D; Kavan, P; Maroun, J; Nanji, S; Roberge, D; Samson, B; Seal, M; Shabana, W; Simunovic, M; Snow, S; Tehfe, M; Thirlwell, M; Tsvetkova, E; Vickers, M; Vuong, T; Goodwin, R

    2016-02-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

  20. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers

    PubMed Central

    Di Valentin, T.; Asmis, T.; Asselah, J.; Aubin, F.; Aucoin, N.; Berry, S.; Biagi, J.; Booth, C.M.; Burkes, R.; Coburn, N.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Frechette, D.; Goel, R.; Gray, S.; Hammad, N.; Jonker, D.; Kavan, P.; Maroun, J.; Nanji, S.; Roberge, D.; Samson, B.; Seal, M.; Shabana, W.; Simunovic, M.; Snow, S.; Tehfe, M.; Thirlwell, M.; Tsvetkova, E.; Vickers, M.; Vuong, T.; Goodwin, R.

    2016-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17–19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  1. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  2. Paediatric rectal prolapse in Rwanda.

    PubMed Central

    Chaloner, E J; Duckett, J; Lewin, J

    1996-01-01

    During the 1994 crisis in Rwanda, a high incidence of full-thickness rectal prolapse was noted among the refugee children in the south-west of the country. The prolapses arose as a result of acute diarrhoeal illness superimposed on malnutrition and worm infestation. We used a modification of the Thiersch wire technique in 40 of these cases during two months working in a refugee camp. A catgut pursestring was tied around the anal margin under local, regional or general anaesthesia. This was effective in achieving short-term control of full-thickness prolapse until the underlying illness was corrected. Under the circumstances, no formal follow-up could be arranged; however, no complications were reported and only one patient presented with recurrence. Images Figure 1 PMID:9014879

  3. [Nuclear morphology in false negative and negative rectal biopsies (author's transl)].

    PubMed

    Rilke, F; Clemente, C; Pilotti, S

    1975-01-01

    An typical nuclear structure consisting of a cribriform and condensed chromatin pattern with hyperchromasia, a small nucleolus and a moderately increased nuclear-cytoplasmic ratio was observed in the epithelial cells of the crypts and in the stromal and muscular cells of 51 out of 70 oncologically negative biopsies of the rectal mucosa. The subsequent retrieval of all clinical and histologia data revealed that the 51 cases included 39 of adenocarcinoma of the large intestine either present (15 cases) at a variable distance from the false negative biopsy or removed previously (24 cases), 7 of extra-intestinal malignant tumor (parotid gland, urinary bladder, endometrium, breast, stomach, metastatic, anus) and 5 with benign conditions of the large intestine. Of the remaining 19 cases whose biopsies did not reveal the atypical nuclear structure 16 had benign lesions of the large intestine and nowhere evidence of malignancy, two had an adenocarcinoma of the large bowel (one present and one removed previously) and one a carcinoma of the anus. In the rectal biopsies examined the atypical nuclear structure was detected in 93.9% of the cases with a malignant tumor either present or removed previously and in 19% of the cases with benign conditions. The morphologic evidence indicated that the atypical nuclear structure was compatible with a possible distrubance of the mitotic cycle since the findings were restricted to the generative compartment of rectal epithelium. The results are discussed in connection with their possible practical use as a diagnostic aid in the evaluation and interpretation of false negative and negative rectal biopsies as well as with their possible significance in the biology of tumor-bearing hosts.

  4. A probabilistic gastrointestinal tract dosimetry model

    NASA Astrophysics Data System (ADS)

    Huh, Chulhaeng

    In internal dosimetry, the tissues of the gastrointestinal (GI) tract represent one of the most radiosensitive organs of the body with the hematopoietic bone marrow. Endoscopic ultrasound is a unique tool to acquire in-vivo data on GI tract wall thicknesses of sufficient resolution needed in radiation dosimetry studies. Through their different echo texture and intensity, five layers of differing echo patterns for superficial mucosa, deep mucosa, submucosa, muscularis propria and serosa exist within the walls of organs composing the alimentary tract. Thicknesses for stomach mucosa ranged from 620 +/- 150 mum to 1320 +/- 80 mum (total stomach wall thicknesses from 2.56 +/- 0.12 to 4.12 +/- 0.11 mm). Measurements made for the rectal images revealed rectal mucosal thicknesses from 150 +/- 90 mum to 670 +/- 110 mum (total rectal wall thicknesses from 2.01 +/- 0.06 to 3.35 +/- 0.46 mm). The mucosa thus accounted for 28 +/- 3% and 16 +/- 6% of the total thickness of the stomach and rectal wall, respectively. Radiation transport simulations were then performed using the Monte Carlo N-particle transport code (MCNP) 4C transport code to calculate S values (Gy/Bq-s) for penetrating and nonpenetrating radiations such as photons, beta particles, conversion electrons and auger electrons of selected nuclides, I123, I131, Tc 99m and Y90 under two source conditions: content and mucosa sources, respectively. The results of this study demonstrate generally good agreement with published data for the stomach mucosa wall. The rectal mucosa data are consistently higher than published data compared with the large intestine due to different radiosensitive cell thicknesses (350 mum vs. a range spanning from 149 mum to 729 mum) and different geometry when a rectal content source is considered. Generally, the ICRP models have been designed to predict the amount of radiation dose in the human body from a "typical" or "reference" individual in a given population. The study has been performed to

  5. How to Use Rectal Suppositories Properly

    MedlinePlus

    ... Lubricate the suppository tip with a water-soluble lubricant such as K-Y Jelly, not petroleum jelly (Vaseline). If you do not have this lubricant, moisten your rectal area with cool tap water. ...

  6. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. American Society of Colon and Rectal Surgeons

    MedlinePlus

    ... Resource Library Brochures and Product Store Career Center DC&R Journal Access Member Directory Educational Resources American ... Care After Colon and Rectal Cancer Crohn’s Disease DC&R Journal Diseases and Conditions Find A Surgeon ...

  8. Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

    PubMed

    Giordani, Erika; Zoratto, Federica; Strudel, Martina; Papa, Anselmo; Rossi, Luigi; Minozzi, Marina; Caruso, Davide; Zaccarelli, Eleonora; Verrico, Monica; Tomao, Silverio

    2016-01-01

    Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

  9. Robotic rectal surgery: State of the art.

    PubMed

    Staderini, Fabio; Foppa, Caterina; Minuzzo, Alessio; Badii, Benedetta; Qirici, Etleva; Trallori, Giacomo; Mallardi, Beatrice; Lami, Gabriele; Macrì, Giuseppe; Bonanomi, Andrea; Bagnoli, Siro; Perigli, Giuliano; Cianchi, Fabio

    2016-11-15

    Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words "rectum", "rectal", "cancer", "laparoscopy", "robot". After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients.

  10. Management of rectal varices in portal hypertension

    PubMed Central

    Al Khalloufi, Kawtar; Laiyemo, Adeyinka O

    2015-01-01

    Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed. PMID:26730278

  11. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  12. Differences in microbial signatures between rectal mucosal biopsies and rectal swabs.

    PubMed

    Araújo-Pérez, Félix; McCoy, Amber N; Okechukwu, Charles; Carroll, Ian M; Smith, Kevin M; Jeremiah, Kim; Sandler, Robert S; Asher, Gary N; Keku, Temitope O

    2012-01-01

    There is growing evidence the microbiota of the large bowel may influence the risk of developing colorectal cancer as well as other diseases including type-1 diabetes, inflammatory bowel diseases and irritable bowel syndrome. Current sampling methods to obtain microbial specimens, such as feces and mucosal biopsies, are inconvenient and unappealing to patients. Obtaining samples through rectal swabs could prove to be a quicker and relatively easier method, but it is unclear if swabs are an adequate substitute. We compared bacterial diversity and composition from rectal swabs and rectal mucosal biopsies in order to examine the viability of rectal swabs as an alternative to biopsies. Paired rectal swabs and mucosal biopsy samples were collected in un-prepped participants (n = 11) and microbial diversity was characterized by Terminal Restriction Fragment Length polymorphism (T-RFLP) analysis and quantitative polymerase chain reaction (qPCR) of the 16S rRNA gene. Microbial community composition from swab samples was different from rectal mucosal biopsies (p = 0.001). Overall the bacterial diversity was higher in swab samples than in biopsies as assessed by diversity indexes such as: richness (p = 0.01), evenness (p = 0.06) and Shannon's diversity (p = 0.04). Analysis of specific bacterial groups by qPCR showed higher copy number of Lactobacillus (p < 0.0001) and Eubacteria (p = 0.0003) in swab samples compared with biopsies. Our findings suggest that rectal swabs and rectal mucosal samples provide different views of the microbiota in the large intestine.

  13. Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere®) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases

    PubMed Central

    Lo, Yuan-Hao; Tsai, Ming-Tsun; Kuo, Chen-Yu; Liu, Wen-Sheng; Lee, Rheun-Chuan; Yeh, Yi-Chen; Li, Chung-Pin; Chen, Jinn-Yang; Chao, Yee

    2012-01-01

    The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere®) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication. PMID:23986828

  14. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers

    PubMed Central

    Saadi, Amel; Shannon, Nicholas B.; Lao-Sirieix, Pierre; O’Donovan, Maria; Walker, Elaine; Clemons, Nicholas J.; Hardwick, James S.; Zhang, Chunsheng; Das, Madhumita; Save, Vicki; Novelli, Marco; Balkwill, Frances; Fitzgerald, Rebecca C.

    2010-01-01

    The stromal compartment is increasingly recognized to play a role in cancer. However, its role in the transition from preinvasive to invasive disease is unknown. Most gastrointestinal tumors have clearly defined premalignant stages, and Barrett’s esophagus (BE) is an ideal research model. Supervised clustering of gene expression profiles from microdissected stroma identified a gene signature that could distinguish between BE metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). EAC patients overexpressing any of the five genes (TMEPAI, JMY, TSP1, FAPα, and BCL6) identified from this stromal signature had a significantly poorer outcome. Gene ontology analysis identified a strong inflammatory component in BE disease progression, and key pathways included cytokine–cytokine receptor interactions and TGF-β. Increased protein levels of inflammatory-related genes significantly up-regulated in EAC compared with preinvasive stages were confirmed in the stroma of independent samples, and in vitro assays confirmed functional relevance of these genes. Gene set enrichment analysis of external datasets demonstrated that the stromal signature was also relevant in the preinvasive to invasive transition of the stomach, colon, and pancreas. These data implicate inflammatory pathways in the genesis of gastrointestinal tract cancers, which can affect prognosis. PMID:20080664

  15. Robotic rectal surgery: State of the art

    PubMed Central

    Staderini, Fabio; Foppa, Caterina; Minuzzo, Alessio; Badii, Benedetta; Qirici, Etleva; Trallori, Giacomo; Mallardi, Beatrice; Lami, Gabriele; Macrì, Giuseppe; Bonanomi, Andrea; Bagnoli, Siro; Perigli, Giuliano; Cianchi, Fabio

    2016-01-01

    Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words “rectum”, “rectal”, “cancer”, “laparoscopy”, “robot”. After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients. PMID:27895814

  16. Scintigraphic demonstration of gastrointestinal bleeding due to mesenteric varices

    SciTech Connect

    Hansen, M.E.; Coleman, R.E. )

    1990-07-01

    Mesenteric varices can appear as massive, acute lower gastrointestinal bleeding. The small bowel or colon may be involved, varices usually developing at sites of previous surgery or inflammation in patients with portal hypertension. Two patients with alcoholic cirrhosis and protal hypertension presented with rectal bleeding. Tc-99m RBC studies demonstrated varices and extravasation into the adjacent bowel. The varices were documented by mesenteric angiography. Characteristic features of Tc-99m labeled RBC studies can identify mesenteric varices as the cause of intestinal bleeding and localize the abnormal vessels.

  17. Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts

    PubMed Central

    Yam, Gary Hin-Fai; Williams, Geraint P.; Setiawan, Melina; Yusoff, Nur Zahirah Binte M.; Lee, Xiao-wen; Htoon, Hla Myint; Zhou, Lei; Fuest, Matthias; Mehta, Jodhbir S.

    2017-01-01

    Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density. PMID:28349952

  18. Stromal Cell Subsets Directing Neonatal Spleen Regeneration

    PubMed Central

    Tan, Jonathan K. H.; Watanabe, Takeshi

    2017-01-01

    Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A failure for LTo to receive appropriate activating signals during embryogenesis through lymphotoxin engagement leads to a complete cessation of lymph node (LN) and Peyer’s patch development, identifying LTo as a key stromal population for lymphoid tissue organogenesis. However, little is known about the equivalent stromal cells that induce spleen development. Here, by dissociating neonatal murine spleen stromal tissue for re-aggregation and transplant into adult mouse recipients, we have identified a MAdCAM-1+CD31+CD201+ spleen stromal organizer cell-type critical for new tissue formation. This finding provides an insight into the regulation of post-natal spleen tissue organogenesis, and could be exploited in the development of spleen regenerative therapies. PMID:28067323

  19. Pathological analysis of collision (double primary) cancer in the upper digestive tract concomitant with gastric stromal tumor: a case report

    PubMed Central

    Sun, Xun; Zou, Yabin; Hao, Yueming; Cheng, Hongjing; Zhou, Changli; Meng, Xiangwei

    2015-01-01

    Carcinoma of the esophagus and cardiac cancer are common malignancies, while multiple primary cancers in the esophagus and cardia is rarely encountered and easily misdiagnosed. Multiple primary cancers mean the same organs (tissues) or different organs (tissues) have two or more than two primary malignant tumors at the same time or in sequence in the same individual. The case below of two independent primary lesions is double primary carcinoma which meets the diagnosis standard of multiple primary cancers. Gastrointestinal stromal tumor is the most common stromal tumor, which is usually considered as originating from Cajal cells in the gastrointestinal tract or mesenchymal stem cells with the mutation of KIT or PDGFRA gene. Study on stromal tumor with digestive tract cancer is less both at home and abroad, while double primary carcinoma with stromal tumor is rare, which has not been reported at present. Although scholars have different viewpoints on the prognosis, but the full understanding of this disease can be as a warning for the future work and to avoid misdiagnosis. PMID:26722567

  20. Primary gastrointestinal lymphoma

    PubMed Central

    Ghimire, Prasanna; Wu, Guang-Yao; Zhu, Ling

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific, thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways. PMID:21390139

  1. Advances in gastrointestinal bleeding.

    PubMed

    Lanas, Ángel

    2016-09-01

    The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations.

  2. Radiologic diagnosis of gastrointestinal perforation.

    PubMed

    Rubesin, Stephen E; Levine, Marc S

    2003-11-01

    Perforations of the gastrointestinal tract have many causes. Holes in the wall of gastrointestinal organs can be created by blunt or penetrating trauma, iatrogenic injury, inflammatory conditions that penetrate the serosa or adventitia, extrinsic neoplasms that invade the gastrointestinal tract, or primary neoplasms that penetrate outside the wall of gastrointestinal organs. This article provides a radiologic approach for investigating the wide variety of gastrointestinal perforations. General principles about contrast agents and studies are reviewed, and then perforations in specific gastrointestinal organs are discussed.

  3. RECTAL IMPACTION DUE TO PRICKLY PEAR SEEDS BEZOAR: A CASE REPORT.

    PubMed

    Marchese, S; Bertucci, B; Manti, F; Berritto, D; Roperto, A G; Tamburrini, S

    2015-01-01

    Fecal impaction is the third cause of lower gastrointestinal tract obstruction after strictures for colon cancer and postoperative adhesions. A rapid diagnosis is necessary to avoid complications due to intestinal obstruction. Rectal phytobezoar due to prickly pear fruit seeds are an extremely rare entity, in the literature about twenty similar cases are described. Prickly pears are common in many countries, even in the Mediterranean area. When the ingestion of their fruit is excessive, this can be harmful, leading to the formation of phytobezoar causing fecal impaction. We describe the first case of phytobezoar due to prickly pear fruit seeds in continental Europe: a 76-year-old Italian female who ingested almost 40 prickly pear fruit leading to the composition of a large rectal phytobezoar. The patient presented clinically with fecal impaction, diagnosed by imaging and successfully treated by rectal irrigation and manual disimpaction. Our aim is to remind the physicians of these risks in evaluating patients with intestinal obstruction, when there is positive anamnesis for provenience from some areas in which these fruits are eaten. We also want to underline the role of Imaging Multi Detector Computed Tomography (MDCT) in the diagnosis of these very uncommon entities.

  4. Low rectal cancer: Sphincter preserving techniques-selection of patients, techniques and outcomes.

    PubMed

    Dimitriou, Nikoletta; Michail, Othon; Moris, Dimitrios; Griniatsos, John

    2015-07-15

    Low rectal cancer is traditionally treated by abdominoperineal resection. In recent years, several new techniques for the treatment of very low rectal cancer patients aiming to preserve the gastrointestinal continuity and to improve both the oncological as well as the functional outcomes, have been emerged. Literature suggest that when the intersphincteric resection is applied in T1-3 tumors located within 30-35 mm from the anal verge, is technically feasible, safe, with equal oncological outcomes compared to conventional surgery and acceptable quality of life. The Anterior Perineal PlanE for Ultra-low Anterior Resection technique, is not disrupting the sphincters, but carries a high complication rate, while the reports on the oncological and functional outcomes are limited. Transanal Endoscopic MicroSurgery (TEM) and TransAnal Minimally Invasive Surgery (TAMIS) should represent the treatment of choice for T1 rectal tumors, with specific criteria according to the NCCN guidelines and favorable pathologic features. Alternatively to the standard conventional surgery, neoadjuvant chemo-radiotherapy followed by TEM or TAMIS seems promising for tumors of a local stage T1sm2-3 or T2. Transanal Total Mesorectal Excision should be performed only when a board approved protocol is available by colorectal surgeons with extensive experience in minimally invasive and transanal endoscopic surgery.

  5. Low rectal cancer: Sphincter preserving techniques-selection of patients, techniques and outcomes

    PubMed Central

    Dimitriou, Nikoletta; Michail, Othon; Moris, Dimitrios; Griniatsos, John

    2015-01-01

    Low rectal cancer is traditionally treated by abdominoperineal resection. In recent years, several new techniques for the treatment of very low rectal cancer patients aiming to preserve the gastrointestinal continuity and to improve both the oncological as well as the functional outcomes, have been emerged. Literature suggest that when the intersphincteric resection is applied in T1-3 tumors located within 30-35 mm from the anal verge, is technically feasible, safe, with equal oncological outcomes compared to conventional surgery and acceptable quality of life. The Anterior Perineal PlanE for Ultra-low Anterior Resection technique, is not disrupting the sphincters, but carries a high complication rate, while the reports on the oncological and functional outcomes are limited. Transanal Endoscopic MicroSurgery (TEM) and TransAnal Minimally Invasive Surgery (TAMIS) should represent the treatment of choice for T1 rectal tumors, with specific criteria according to the NCCN guidelines and favorable pathologic features. Alternatively to the standard conventional surgery, neoadjuvant chemo-radiotherapy followed by TEM or TAMIS seems promising for tumors of a local stage T1sm2-3 or T2. Transanal Total Mesorectal Excision should be performed only when a board approved protocol is available by colorectal surgeons with extensive experience in minimally invasive and transanal endoscopic surgery. PMID:26191350

  6. Novel radiation techniques for rectal cancer

    PubMed Central

    2014-01-01

    The concepts for management of rectal cancer have changed drastically over the past few years. Through national bowel cancer screening programmes in the Western countries and the increasing use of endoscopic procedures as diagnostic tool, there is increase in detection of rectal cancer in early stages. There is increase in ageing population worldwide but more so in Western countries. In addition, there is realisation of harm from extirpative surgical procedures which are directed towards managing advanced rectal cancer in the past. Increase in cost of health care burden has also led the investigators to seek alternative treatment options which are effective, safe and cost effective. There are several modern radiation techniques which fits this bill and we need to be aware of newer novel radiation techniques to fulfil this gap. PMID:24982769

  7. Rectal mucosa in cows' milk allergy.

    PubMed Central

    Iyngkaran, N; Yadav, M; Boey, C G

    1989-01-01

    Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants. PMID:2817945

  8. Endotoxin in the conscious piglet: its effects on some general and gastrointestinal myoelectrical parameters.

    PubMed

    De Saedeleer, V; Wechsung, E; Houvenaghel, A

    1991-01-01

    The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 micrograms/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4-5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose-dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 micrograms/kg) or a leukocytosis (1 microgram/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 micrograms/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these.

  9. Primary Transanal Management of Rectal Atresia in a Neonate.

    PubMed

    M, Braiek; A, Ksia; I, Krichen; S, Belhassen; K, Maazoun; S, Ben Youssef; N, Kechiche; M, Mekki; A, Nouri

    2016-01-01

    Rectal atresia (RA) with a normal anus is a rare anomaly. We describe a case of rectal atresia in a newborn male presenting with an abdominal distension and failure of passing meconium. The rectal atresia was primarily operated by transanal route.

  10. Inflammatory stromal keratopathies: medical management of stromal keratomalacia, stromal abscesses, eosinophilic keratitis, and band keratopathy in the horse.

    PubMed

    Brooks, Dennis E

    2004-08-01

    This article discusses the diagnosis and medical treatment of stromal keratomalacia or "melting ulcers," stromal abscesses, eosinophilic keratitis (EK), and calcific band keratopathy. These are common and important inflammatory keratopathies of the equine corneal stroma. Keratomalacia and stromal abscesses are associated with infection, leukocytic invasion of the stroma, and loss of tissue and tear film proteinase homeostasis. Eosinophils infiltrate the stroma in response to unknown stimuli in EK. Calcium is deposited in the stroma and epithelium secondary to chronic equine recurrent uveitis in calcific band keratopathy. They are all associated with varying degrees of iridocyclitis.

  11. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  12. Massive zosteriform cutaneous metastasis from rectal carcinoma.

    PubMed

    Damin, D C; Lazzaron, A R; Tarta, C; Cartel, A; Rosito, M A

    2003-07-01

    A 44-year-old man presented with a large and rapidly growing skin lesion approximately six months after resection of a rectal carcinoma. The lesion measured 40 cm in size, extended from the suprapubic area to the proximal half of the left groin, and showed a particular zosteriform aspect. Biopsy confirmed a metastatic skin adenocarcinoma. Cutaneous metastases from rectal cancer are very uncommon. Their gross appearance is not distinctive, although the skin tumors are usually solid, small (less than 5 cm) and painless nodules or papules. Early biopsies for suspicious skin lesions are needed in patients with a history of colorectal cancer.

  13. Transanal Approach to Rectal Polyps and Cancer

    PubMed Central

    Rai, Vinay; Mishra, Nitin

    2016-01-01

    A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations. PMID:26929754

  14. Neoadjuvant Treatment in Rectal Cancer: Actual Status

    PubMed Central

    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  15. [Subepithelial tumors of the gastrointestinal tract].

    PubMed

    Stupnik, Silvio; Rafaelli, Claudio; González, Graciela Osorio; Pestalardo, María Luján; Quesada, Matías; Viúdez, Pedro

    2009-06-01

    The subepithelial lesions of the gastrointestinal tract are related to mesenchymal tumors and 80% of them are GIST (gastrointestinal stromal tumors). However, there are also other tumors, such as: leiomyomas, schwannomas, lipomas, glomus tumors, carcinoid tumors, aberrant pancreas and polyps or inflammatory tumors. Diagnosis of submucosal tumors is often performed during routine endoscopic examination, they are frequently located at the stomach and in most cases are clinically evidenced by their complications. Endoscopic ultrasonography (EUS) is the elected method for their staging; but other imaging diagnosis methods include computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography scan (PET). The differential diagnosis is made by inmunohistochemical techniques, revealing in the GIST the expression of the antigen CD117, and prognostic factors are determined by size and mitotic index. Surgery is the recommended therapeutic, although in small lesions not exceeding 2 cm it has also been suggested the endoscopic resection guided by EUS and a watchful behaviour based on periodical controls in lesions with benignity criteria. The series here exhibited (2 GIST 1 lyposarcoma, 1 schwannoma and 1 inflammatory fibroid polyp) shows that all these tumors were symptomatic; have been diagnosed using endoscopy and recognized by means of histopathology and immunohistochemical analysis after surgery.

  16. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  17. Diversity of Duodenal and Rectal Microbiota in Biopsy Tissues and Luminal Contents in Healthy Volunteers.

    PubMed

    Li, Gangping; Yang, Min; Zhou, Kan; Zhang, Lei; Tian, Lugao; Lv, Shangze; Jin, Yu; Qian, Wei; Xiong, Hanhua; Lin, Rong; Fu, Yu; Hou, Xiaohua

    2015-07-01

    The diverse microbial communities that colonize distinct segments of the gastrointestinal tract are intimately related to aspects of physiology and the pathology of human health. However, most recent studies have focused on the rectal or fecal microbiota, and the microbial signature of the duodenum is poorly studied. In this study, we compared the microbiota in duodenal and rectal samples to illustrate the characteristic microbial signatures of the duodenum in healthy adults. Nine healthy volunteers donated biopsies and luminal contents from the duodenum and rectum. To determine the composition and diversity of the microbiota, 454- pyrosequencing of bacterial 16S rRNA was performed and multiple bioinformatics analyses were applied. The α-diversity and phylogenetic diversity of the microbiota in the duodenal samples were higher than those of the rectal samples. There was higher biodiversity among the microbiota isolated from rectal biopsies than feces. Proteobacteria were more highly represented in the duodenum than in the rectum, both in the biopsies and in the luminal contents from the healthy volunteers (38.7% versus 12.5%, 33.2% versus 5.0%, respectively). Acinetobacter and Prevotella were dominant in the duodenum, whereas Bacteroides and Prevotella were dominant in the rectum. Additionally, the percentage of OTUs shared in biopsy groups was far higher than in the luminal group (43.0% versus 26.8%) and a greater number of genera was shared among the biopsies than the luminal contents. Duodenal samples demonstrated greater biological diversity and possessed a unique microbial signature compared with the rectum. The mucosa-associated microbiota was more relatively conserved than luminal samples.

  18. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  19. Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer

    SciTech Connect

    Ishikawa, Hitoshi; Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Kamada, Tadashi; Hirasawa, Naoki; Yanagi, Takeshi; Mizoe, Jun-Etsu; Akakura, Koichiro; Suzuki, Hiroyoshi; Shimazaki, Jun; Tsujii, Hirohiko

    2006-11-15

    Purpose: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. Results: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 {+-} 5.6% with toxicity; 11.4 {+-} 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. Conclusions: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.

  20. Gastrointestinal leiomyosarcoma in a pygmy sperm whale (Kogia breviceps).

    PubMed

    Leone, Angelique; Dark, Michael; Kondo, Hirotaka; Rotstein, David S; Kiupel, Matti; Walsh, Michael T; Erlacher-Reid, Claire; Gordon, Nadia; Conway, Julia A

    2013-09-01

    An adult male pygmy sperm whale (Kogia breviceps) was stranded within a tidal pool on Fernandina Beach on the north Florida Atlantic coast (USA) and expired soon after discovery. Necropsy findings included a small intestinal mass markedly expanding the intestinal wall and partially obstructing the lumen. This finding likely led to the malnutrition and ultimately the stranding of this whale. The differential diagnoses for the mass based on gross evaluation included a duodenal adenocarcinoma, leiomyoma/sarcoma, gastrointestinal stroma tumor, and benign/malignant peripheral nerve sheath tumor, previously referred to as neurofibromas or schwannomas. The mass was presumptively diagnosed as a leiomyosarcoma via routine histopathology and confirmed by immunoreactivity for desmin and smooth actin (SMA). KIT, a gene name for CD 117, was negative, excluding a gastrointestinal stromal tumor (GIST). Leiomyosarcomas have been reported within numerous wild and domestic species, although this is the first reported case of any neoplasm in a pygmy sperm whale (K. breviceps).

  1. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

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

  2. Osteoporosis and Gastrointestinal Disease

    PubMed Central

    Weinerman, Stuart

    2010-01-01

    Gastrointestinal disease is often overlooked or simply forgotten as a cause of osteoporosis. Yet, the consequences of osteoporotic fractures can be devastating. Although the bulk of the published experience regarding osteoporosis is derived from the postmenopausal population, this review will focus on gastrointestinal disorders implicated in osteoporosis, with an emphasis on inflammatory bowel disease and celiac disease. The unique aspects of gastrointestinal diseases associated with osteoporosis include early onset of disease (and, therefore, prolonged exposure to risk factors for developing osteoporosis, particularly with inflammatory bowel disease and celiac disease), malabsorption, and maldigestion of nutrients necessary for bone health and maintenance (eg, calcium, vitamin D), as well as the impact of glucocorticoids. These factors, when added to smoking, a sedentary lifestyle, hypogonadism, and a family history of osteoporosis, accumulate into an imposing package of predictors for osteoporotic fracture. This paper will review the identification and treatment strategies for patients with gastrointestinal disorders and osteoporosis. PMID:20978554

  3. Rectal bezoars due to pumpkin seeds.

    PubMed

    Mirza, Mohammad Salman; Al-Wahibi, Khalifa; Baloch, Shafiq; Al-Qadhi, Hani

    2009-01-01

    Rectal bezoars commonly occur due to seeds, especially in children living in countries south of the Mediterranean and in the Middle-East. Dried seeds are considered a delicacy and consumed widely. Inadequate chewing or hastily eating without removing the hull may lead to their impaction as bezoars, which may require manual removal under general anaesthesia.

  4. Vasculitis and gastrointestinal involvement.

    PubMed

    Casella, G; Bronzino, B; Cutrino, L; Montani, N; Somma, A; Baldini, V

    2006-06-01

    The incidence of gastrointestinal involvement is relatively observed in patients with vasculitis processes. Vasculitis can be primary (necrotising or hypersensitivity) or secondary to another primary disease. Gastrointestinal involvement is present in up to 50% of the various forms of systemic vasculitis. Primary or secondary vasculitic process, according to the classification in necrotizing and hypersensitivity vasculitis, are described in this paper. A review of the literature on the the subject is also presented.

  5. [Is there a relationship between rectal colonization and nosocomial infection of patients in intensive care unit?].

    PubMed

    Yeşilbağ, Zuhal; Çağatay, Arif Atahan; Karadeniz, Aslı; Başaran, Seniha; Orhun, Günseli; Ergin Özcan, Perihan; Özsüt, Halit; Eraksoy, Haluk

    2015-07-01

    -resistant K.pneumoniae (1%), respectively. The number of microorganisms isolated from rectal swab cultures on the following days have increased, and on the 7th day, the rate of the patients with rectal colonization ascended to 72%. Out of 80 patients, 52 (65%) had nosocomial infections in the follow-up and the mean duration of infection development was 11.8±9.9 days in these patients. Patients with and without rectal colonization were compared in terms of subsequent nosocomial infection rates. While no statistically significant difference has been detected between two groups on the day of 0, patients with rectal colonization detected on the day of 3 and 7, had a significantly higher incidence of nosocomial infections (p=0.02, p=0.01). Among the patients with ESBL-positive GNB, carbapenem-resistant K.pneumoniae, carbapenem-resistant P.aeruginosa and VRE infections, the same microorganisms have been isolated in the rectal swab cultures taken before the development of infection. This result was statistically significant for each of these microorganisms (p=0.00-0.03). However, such a correlation was not observed for Acinetobacter infections. Since MRSA infections developed in only two patients, no istatistical analysis has been done for this microorganism. In conclusion, our data suggest that MDR microorganisms that cause nosocomial infections, initially colonize the gastrointestinal tract, and early detection of colonized patients in ICUs may help an effective infection control by preventing the spread of these resistant microorganisms.

  6. Asbestos and Gastrointestinal Cancer

    PubMed Central

    Morgan, Robert W.; Foliart, Donna E.; Wong, Otto

    1985-01-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, we listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, we calculated summary SMRs for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMRs remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. Based on the results after reanalysis, the elevations in summary SMRs for stomach and total gastrointestinal tract cancer are of a magnitude that could result from diagnostic and investigator error. We conclude that more studies are required before stomach and colorectal cancers are documented as asbestos-related diseases. PMID:4036114

  7. Gastroduodenal adenocarcinomas and rectal adenoma in a cougar (Felis concolor) infected with Helicobacter-like organisms and spirochetes.

    PubMed

    Yamazaki, Yoshikazu; Aono, Itsushi; Ohya, Tatsuo; Shibahara, Tomoyuki; Kadota, Koichi

    2002-02-01

    A 14-year-old female cougar died from gastroduodenal adenocarcinomas and rectal adenoma. At necropsy, polypoid tumor masses of various sizes were scattered on the mucosal surfaces of the stomach, duodenum, and rectum. Histologically, the gastric tumor was diagnosed as an intestinal type adenocarcinoma and the tumor cells metastasized to the mesenteric lymph nodes, spleen, and lung. Helicobacter-like organisms were detected in the lumina lined by foveolar epithelium. In the duodenum, the carcinoma cells were localized in the limina propria and many of them were intensely positive for proliferating cell nuclear antigen (PCNA). In contrast, the rectal adenoma had a lower number of PCNA-positive cells. In the rectum, chronic inflammation with numerous spirochetes was also noted. These results indicated that the occurrence of the gastrointestinal tumors might be associated with the bacterial infection described above.

  8. Angiography and the gastrointestinal bleeder

    SciTech Connect

    Baum, S.

    1982-05-01

    The role of angiography in the diagnosis and treatment of gastrointestinal hemorrhage is discussed. Three categories of gastrointestinal bleeding are considered: upper gastrointestinal bleeding due to gastroesophageal varices, upper gastrointestinal bleeding of arterial or capillary origin, and lower gastrointestinal bleeding. The advantages and disadvantages of angiography are compared with those of radionuclide scanning and endoscopy or colonoscopy. It is anticipated that, as radionuclide scans are more widely employed, angiography will eventually be performed only in those patients with positive scans.

  9. Comparison between core temperatures measured telemetrically using the CorTemp® ingestible temperature sensor and rectal temperature in healthy Labrador retrievers.

    PubMed

    Osinchuk, Stephanie; Taylor, Susan M; Shmon, Cindy L; Pharr, John; Campbell, John

    2014-10-01

    This study evaluated the CorTemp(®) ingestible telemetric core body temperature sensor in dogs, to establish the relationship between rectal temperature and telemetrically measured core body temperature at rest and during exercise, and to examine the effect of sensor location in the gastrointestinal (GI) tract on measured core temperature. CorTemp(®) sensors were administered orally to fasted Labrador retriever dogs and radiographs were taken to document sensor location. Core and rectal temperatures were monitored throughout the day in 6 resting dogs and during a 10-minute strenuous retrieving exercise in 6 dogs. Time required for the sensor to leave the stomach (120 to 610 min) was variable. Measured core temperature was consistently higher than rectal temperature across all GI locations but temperature differences based on GI location were not significant (P = 0.5218). Resting dogs had a core temperature that was on average 0.4°C above their rectal temperature with 95% limits of agreement (LoA) between 1.2°C and -0.5°C. Core temperature in exercising dogs was on average 0.3°C higher than their concurrent rectal temperature, with LoA of +1.6°C and -1.1°C.

  10. Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

  11. Nutritional status and related factors of patients with advanced gastrointestinal cancer.

    PubMed

    Zhang, Liyan; Lu, Yuhan; Fang, Yu

    2014-04-14

    The scored Patient-Generated Subjective Global Assessment (PG-SGA) is considered to be the most appropriate tool for detecting malnutrition in cancer patients. In particular, malignant tumours derived from the gastrointestinal tract may impair nutrient intake and absorption and cause malnutrition. We carried out a cross-sectional study to assess the nutritional status and related factors of patients with gastrointestinal cancer. Nutritional status was determined using the scored PG-SGA in patients (n 498) with advanced gastrointestinal cancer admitted to the Gastrointestinal Medical Oncology Unit at Beijing Cancer Hospital between 1 August 2012 and 28 February 2013. The possible related factors including age, sex, hospitalisation frequency and pathology were explored. We found that 98% of the patients required nutrition intervention and 54% of the patients required improved nutrition-related symptom management and/or urgent nutritional support (PG-SGA score ≥9). Factors related to malnutrition were age (r 0.103, P<0.01), hospitalisation frequency (r -0.196, P<0.01) and sex (the prevalence of malnutrition was higher in men than in women (9.88 v. 8.54, P<0.01)). Patients with rectal cancer had a lower risk of malnutrition than patients with other types of gastrointestinal cancer (F=35.895, P<0.01). More attention should be paid to the nutritional status of gastrointestinal patients, especially those at a higher risk of malnutrition, such as elderly patients, those hospitalised for the first time, male patients and those with other types of gastrointestinal cancer except rectal cancer. The nutritional status of these patients should be evaluated and they should be given proper nutrition education and nutritional support in a timely manner.

  12. Asbestos and gastrointestinal cancer

    SciTech Connect

    Morgan, R.W.; Foliart, D.E.; Wong, O.

    1985-07-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, the authors listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, summary SMRs were calculated for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMR remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. 59 references, 5 tables.

  13. Gastrointestinal Stent Update

    PubMed Central

    2010-01-01

    The use of self-expanding metallic stents in the upper gastrointestinal tract, placed under radiologic imaging or endoscopic guidance, is the current treatment of choice for the palliation of malignant gastrointestinal outlet obstructions. Advances in metallic stent design and delivery systems have progressed to the stage where this treatment is now considered a minimally invasive therapy. Metallic stent placement will broaden further into the field of nonsurgical therapy for the gastrointestinal tract. To date, metallic stents placed in the esophagus, gastric outlet, colorectum, and bile ducts are not intended to be curative, but rather to provide a palliative treatment for obstructions. The evolution of metallic stent technology will render such procedures not only palliative but also therapeutic, by enabling local drug delivery, and the use of biodegradable materials will reduce procedure-related complications. PMID:21103290

  14. Evidence and research in rectal cancer.

    PubMed

    Valentini, Vincenzo; Beets-Tan, Regina; Borras, Josep M; Krivokapić, Zoran; Leer, Jan Willem; Påhlman, Lars; Rödel, Claus; Schmoll, Hans Joachim; Scott, Nigel; Velde, Cornelius Van de; Verfaillie, Christine

    2008-06-01

    The main evidences of epidemiology, diagnostic imaging, pathology, surgery, radiotherapy, chemotherapy and follow-up are reviewed to optimize the routine treatment of rectal cancer according to a multidisciplinary approach. This paper reports on the knowledge shared between different specialists involved in the design and management of the multidisciplinary ESTRO Teaching Course on Rectal Cancer. The scenario of ongoing research is also addressed. In this time of changing treatments, it clearly appears that a common standard for large heterogeneous patient groups have to be substituted by more individualised therapies based on clinical-pathological features and very soon on molecular and genetic markers. Only trained multidisciplinary teams can face this new challenge and tailor the treatments according to the best scientific evidence for each patient.

  15. Transanal local excision of rectal cancer.

    PubMed

    Read, D R; Sokil, S; Ruiz-Salas, G

    1995-01-01

    Twenty-five patients with invasive rectal cancer treated by transanal excision between 1978-1989 are presented. Two patients had poorly differentiated tumours and were converted to abdominoperineal resection and one patient had extensive liver metastases documented preoperatively. The remaining twenty-two, mean age 64 years, fulfilled the criteria for local treatment. Eighty-two percent of tumours were T1 or T2 stage. There was no operative mortality. Six complications in five patients occurred, none requiring surgical intervention. Five patients died of unrelated causes without evidence of recurrence at 4, 4, 14, 26 and 58 months. The length of follow-up for the surviving group (17 patients) was 16 to 115 months (mean 63 months). Two patients developed local recurrence at 32 and 60 months. Transanal excision can be curative for selected rectal cancers.

  16. Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

    PubMed

    Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M; Fujiwara, Toshiyoshi

    2015-03-01

    Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.

  17. Altemeier operation for gangrenous rectal prolapse.

    PubMed

    Abdelhedi, Cherif; Frikha, F; Bardaa, S; Kchaw, A; Mzali, R

    2014-08-08

    A stranguled rectal prolapse is a rare cause of intestinal occlusion. It requires emergency surgery. A patient who underwent emergency perineal proctectomy, the Altemeier operation, combined with diverting loop sigmoid colostomy is described. The postoperative course was uneventful, with an excellent final result after colostomy closure. The successful treatment of this patient illustrates the value of the Altemeier procedure in the difficult and unusual scenario of bowel incarceration.

  18. Increasing trend in retained rectal foreign bodies

    PubMed Central

    Ayantunde, Abraham A; Unluer, Zynep

    2016-01-01

    AIM To highlight the rising trend in hospital presentation of foreign bodies retained in the rectum over a 5-year period. METHODS Retrospective review of the cases of retained rectal foreign bodies between 2008 and 2012 was performed. Patients’ clinical data and yearly case presentation with data relating to hospital episodes were collected. Data analysis was by SPSS Inc. Chicago, IL, United States. RESULTS Twenty-five patients presented over a 5-year period with a mean age of 39 (17-62) years and M: F ratio of 2:1. A progressive rise in cases was noted from 2008 to 2012 with 3, 4, 4, 6, 8 recorded patients per year respectively. The majority of the impacted rectal objects were used for self-/partner-eroticism. The commonest retained foreign bodies were sex vibrators and dildos. Ninty-six percent of the patients required extraction while one passed spontaneously. Two and three patients had retrieval in the Emergency Department and on the ward respectively while 19 patients needed examination under anaesthesia for extraction. The mean hospital stay was 19 (2-38) h. Associated psychosocial issues included depression, deliberate self-harm, illicit drug abuse, anxiety and alcoholism. There were no psychosocial problems identified in 15 patients. CONCLUSION There is a progressive rise in hospital presentation of impacted rectal foreign bodies with increasing use of different objects for sexual arousal. PMID:27830039

  19. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; 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

  20. Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children

    PubMed Central

    Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

    2016-01-01

    Background Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. Objectives This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. Patients and Methods This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. Results The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). Conclusions In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories. PMID:26889398

  1. Case report: Sigmoid strangulation from evisceration through a perforated rectal prolapse ulcer – An unusual complication of rectal prolapse

    PubMed Central

    Li, Jennifer Z.; Kittmer, Tiffaney; Forbes, Shawn; Ruo, Leyo

    2015-01-01

    Introduction Rectal prolapse occurs particularly in elder females and presentation can sometimes lead to complications such as strangulation and evisceration of other organs through the necrotic mucosa. Presentation of case This is a case of a 61 year-old female with rectal prolapse complicated by rectal perforation through which a segment of sigmoid colon eviscerated and became strangulated. This patient initially presented with sepsis requiring ICU admission, but fully recovered following a Hartmann’s procedure with a sacral rectopexy. Discussion Complications of rectal prolapse include incarceration, strangulation, and rarely, perforation with evisceration of other viscera requiring urgent operation. This report provides a brief overview of complications associated with rectal prolapse, reviews similar cases of transrectal evisceration, and discusses the management of chronic rectal prolapse. Conclusion Prompt surgical consult is warranted if any signs or symptoms suggestive of complications from prolapse are present. PMID:25680532

  2. Treatment Option Overview (Gastrointestinal Carcinoid Tumors)

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  3. Treatment Options for Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  4. General Information about Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  5. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    PubMed Central

    Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

    2014-01-01

    Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was

  6. Apollo gastrointestinal analysis

    NASA Technical Reports Server (NTRS)

    Nichols, B. L.; Huang, C. T. L.

    1975-01-01

    Fecal bile acid patterns for the Apollo 17 flight were studied to determine the cause of diarrhea on the mission. The fecal sterol analysis gave no indication of an infectious diarrhea, or specific, or nonspecific etiology occurring during the entire flight. It is assumed that the gastrointestinal problems encountered are the consequences of altered physiology, perhaps secondary to physical or emotional stress of flight.

  7. Pediatric functional gastrointestinal disorders

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional gastrointestinal disorders continue to be a prevalent set of conditions faced by the healthcare team and have a significant emotional and economic impact. In this review, the authors highlight some of the common functional disorders seen in pediatric patients (functional dyspepsia, irrita...

  8. Gastrointestinal endoscopy in pregnancy.

    PubMed

    Savas, Nurten

    2014-11-07

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure.

  9. Gastrointestinal endoscopy in pregnancy

    PubMed Central

    Savas, Nurten

    2014-01-01

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure. PMID:25386072

  10. Gastrointestinal Bleeding in Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1989-01-01

    Describes the scope and importance of gastrointestinal bleeding in runners and other athletes, discussing causes, sites, and implications of exercise-related bleeding. Practical tips to mitigate the problem, potentially more troublesome in women because of lower iron stores, are presented (e.g., gradual conditioning and avoidance of prerace…

  11. Early Experience with Stapled Gastrointestinal Anastomoses in a Nigerian Hospital

    PubMed Central

    Adisa, AO; Olasehinde, O; Arowolo, OA; Alatise, OI; Agbakwuru, EA

    2015-01-01

    Background: Hand-sewn gastrointestinal anastomoses has been the traditional approach to gastrointestinal anastomosis in Nigeria while stapled anastomoses are infrequently performed in few centers. Objectives: To describe the outcome of our initial experience with stapled gastrointestinal anastomoses in a semi-urban patient population. Patients and Methods: Consecutive patients who had stapled gastrointestinal anastomoses between January 2011 and June 2014 in a Nigerian tertiary hospital were prospectively evaluated. Indications for operation, procedures performed and anastomoses constructed and postoperative outcome of each patient were documented. Results: Nineteen patients including seven males and 12 females had stapled anastomoses within the period. Their ages ranged between 41 and 68 (mean 52.5) years. Six (31.6%) Roux-en-Y gastrojejunostomies, 6 (31.6%) ileo-colic, 3 (15.8%) ileo-ileal, 2 (10.5%) colo-colic, and 2 (10.5%) colo-anal anastomoses were performed. Indications include antral gastric cancer in 4 (21.1%), right colon cancer 4 (21.1%), ileal perforations in 3 (15.8%) while 2 (10.5%) each had left colon cancer, common bile duct obstruction, rectal cancer and ruptured appendix. Mean duration of operation was 108 ± 46 min and mean duration of postoperative stay was 5 ± 2.6 days. No intraoperative complications were recorded and no anastomotic leakage occurred. At a median follow-up of 5 months no staple related stricture had occurred. Conclusions: Stapled gastrointestinal anastomoses are associated with a good outcome in our center. We propose a prospective, large-population randomized comparison of the technique with hand-sewn anastomoses. PMID:26425069

  12. Hepatic immune regulation by stromal cells.

    PubMed

    Schildberg, Frank A; Sharpe, Arlene H; Turley, Shannon J

    2015-02-01

    A metabolic organ, the liver also has a central role in tolerance induction. Stromal cells lining the hepatic sinusoids, such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), are the first liver cells to encounter gut-derived and systemic antigens, thereby shaping local and systemic tolerance. Recent studies have demonstrated that stromal cells can modulate immune responses by antigen-dependent and independent mechanisms. Stromal cells interfere with the function of other antigen-presenting cells (APCs) and induce non-responsive T cells as well as regulatory T cells and myeloid-derived suppressor cells (MDSCs). The immunosuppressive microenvironment thus created provides a means to protect the liver from tissue damage. Such tolerized surroundings, however, can be exploited by certain pathogens, promoting persistent liver infections.

  13. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

  14. Ultrasound-mediated gastrointestinal drug delivery

    PubMed Central

    Schoellhammer, Carl M.; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M.; Brugge, William R.; Anderson, Daniel G.; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2016-01-01

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease. PMID:26491078

  15. Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

    2015-01-01

    Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

  16. Management of Rectal Cancer: Short- vs. Long-Course Preoperative Radiation

    SciTech Connect

    Mohiuddin, Mohammed Marks, John; Marks, Gerald

    2008-11-01

    There is considerable debate on the optimum approach to neoadjuvant therapy in rectal cancer. This review of major published studies of short-course preoperative radiation and the more conventional approach of long-course neoadjuvant chemoradiation was undertaken in an effort to understand the potential advantages and disadvantages of each of these approaches. Studies were evaluated with regard to patient selection, clinical outcomes, and toxicities. Short-course preoperative radiation has shown a clear advantage over surgery alone in reducing local recurrence rates and improving survival of patients with rectal cancer. However, studies using short-course preoperative treatment have included a significant number of early (30%; Stage I/II) and more proximal cancers yet appear to have higher positive margin rates, higher abdominoperineal resection rates, and lower aggregate survival than patients treated with long-course neoadjuvant chemoradiation. Although long-course preoperative chemoradiation is associated with higher rates of reversible acute toxicity, there appears to be more significant and a higher rate of late gastrointestinal toxicity observed in short-course preoperative radiation studies. Patient convenience and lower cost of treatment, however, can be a significant advantage in using a short-course treatment schedule. Selective utilization of either of these approaches should be based on extent of disease and goals of treatment. Patients with distal cancers or more advanced disease (T3/T4) appear to have better outcomes with neoadjuvant chemoradiation, especially where downstaging of disease is critical for more complete surgical resection and sphincter preservation.

  17. Prospective Evaluation of Genito-Urinary Function after Laparoscopic Rectal Resection in the Elderly.

    PubMed

    Mari, Giulio; Costanzi, Andrea; Galfrascoli, Elisa; Rosato, Andrea; Crippa, Jacopo; Maggioni, Dario

    2016-01-01

    Laparoscopic anterior rectal resection with total mesorectal excision is related to sexual and urinary disorders. Anastomotic leak and neo-adjuvant radiation therapy are effective factors in worsening pelvic function. We report a series of 50 elderly (age 70) patients who underwent laparoscopic total mesorectal excision inquired about pre and post-operative genito-urinary function. Patients were interviewed preoperatively, 1 and 9 months post-operatively with validated questionnaires about sexual and urinary function and quality of life. They also underwent urofluximetric test with ultrasound measurement of the bladder remnant volume. The geriatric assessment was performed with the BARTHEL index. Urinary and sexual function slightly worsened after surgery although not significantly. Mean Gastrointestinal Quality of Life Indicator score decreased significantly from pre operative levels at 1 month from surgery. BARTHEL index did not change significantly across surgery. Maximum urinary flow, mean urinary flow, bladder residual volume worsened after surgery although not significantly. Laparoscopic anterior rectal resection with total mesorectal excision affects the genito-urinary status of elderly patients. Incidence of severe dysfunctions is similar to normal aged population.

  18. Abdominosacral resection for locally recurring rectal cancer

    PubMed Central

    Belli, Filiberto; Gronchi, Alessandro; Corbellini, Carlo; Milione, Massimo; Leo, Ermanno

    2016-01-01

    AIM To investigate feasibility and outcome of abdominal-sacral resection for treatment of locally recurrent rectal adenocarcinoma. METHODS A population of patients who underwent an abdominal-sacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences. RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55 (range, 38-64). The median operating time was 380 min (range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 mL (range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type II complication according to the Clavien-Dindo classification. Microscopically negative margins (R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a median survival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic. CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy. PMID:28070232

  19. Rectal chlamydia - should screening be recommended in women?

    PubMed

    Andersson, Nirina; Boman, Jens; Nylander, Elisabet

    2017-04-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted infection in Europe and has large impacts on patients' physical and emotional health. Unidentified asymptomatic rectal Chlamydia trachomatis could be a partial explanation for the high Chlamydia trachomatis prevalence. In this study, we evaluated rectal Chlamydia trachomatis testing in relation to symptoms and sexual habits in women and men who have sex with men. Rectal Chlamydia trachomatis prevalence was 9.1% in women and 0.9% in men who have sex with men. None of the patients reported any rectal symptoms; 59.0% of the women with a rectal Chlamydia trachomatis infection denied anal intercourse and 18.8% did not have a urogenital infection; 9.4% did neither have a urogenital infection nor reported anal sex. We suggest that rectal sampling should be considered in women visiting sexually transmitted infection clinics regardless of rectal symptoms and irrespective of anal intercourse, since our data suggest that several cases of rectal Chlamydia trachomatis otherwise would be missed, thus enabling further disease transmission.

  20. Combined modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D; Röedel, Claus; Valentini, Vincenzo

    2010-01-01

    The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  1. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  2. Rectal and appendiceal inflammatory myofibroblastic tumors.

    PubMed

    Khoddami, Maliheh; Sanae, Shahram; Nikkhoo, Bahram

    2006-07-01

    Inflammatory myofibroblastic tumors are neoplasms characterized by spindle cell proliferation and a fiboinflammatory vascular stroma. Herein, we presented the successful treatment of a rectal inflammatory myofibroblastic tumor in an 11-year-old boy who presented with diarrhea and abdominal pain of 1(1/2) months duration and an appendiceal inflammatory myofibroblastic tumor in a 29-year-old man presented with recurrent abdominal pain of two months duration with associated tenderness and rebound tenderness in the right lower abdomen. Histologically, our cases had inflammatory myofibroblastic tumors very similar to that of other sites; the spindle cells were positive for vimentin and muscle-specific actin.

  3. A new 'enterocompressor' to facilitate rectal anastomosis.

    PubMed

    Barraza, R P

    1990-02-01

    A newly devised enterocompressor facilitates low rectal anastomosis in children with Hirschsprung's disease. This simple surgical instrument, composed of two semicylindrical valves, a hinge, and a regulating screw, maintains intestinal anastomoses properly placed and produces spur crushing. In addition, it is inexpensive and reusable. The enterocompressor, used in 33 primary and 15 secondary Duhamel operations, and applied to normalize intestinal transit in 10 colectomies, provided adequate anastomosis and prevented leakage of intestinal contents. This enterocompressor can be used safely in children as young as six months of age.

  4. Gastrointestinal parasite infestation.

    PubMed

    Abd El Bagi, Mohamed E; Sammak, Bassam M; Mohamed, Abdulrahman E; Al Karawi, Mohamed A; Al Shahed, Mona; Al Thagafi, Mohamed A

    2004-03-01

    Twenty-five percent of the world's population could be suffering parasitic infestation. Highest prevalence is in underdeveloped agricultural and rural areas in the tropical and subtropical regions. In some areas incidence may reach 90% of the population. In contrast, some major economic projects intended to promote local development have, paradoxically, caused parasitic proliferation, e.g. bilharziasis in Egypt and Sudan and Chagas disease in Brazil. The commonest cosmopolitan gastrointestinal parasite is Entamoeba histolytica. Some intestinal parasite are endemic in temperate climates, e.g. Entrobius vermicularis. The AIDS epidemic has increased the prevalence and severity of parasitic disease, particularly Strongyloides stercolaris. Tropical parasites are seen in Western people who travel to tropical countries. Radiology has acquired a major role in diagnosis and management of gastrointestinal parasite infestations and their complications.

  5. [Microbiota and gastrointestinal diseases].

    PubMed

    Polanco Allué, I

    2015-12-01

    The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases.

  6. Origin of hemopoietic stromal progenitor cells in chimeras

    SciTech Connect

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-12-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice.

  7. Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration

    PubMed Central

    Peng, Yu-Ching; Levine, Charles M.; Zahid, Sarwar; Wilson, E. Lynette; Joyner, Alexandra L.

    2013-01-01

    The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo. PMID:24218555

  8. Gastrointestinal food allergies.

    PubMed

    Heine, Ralf G

    2015-01-01

    Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development.

  9. Management of gastrointestinal hemorrhage.

    PubMed Central

    Hilsden, R. J.; Shaffer, E. A.

    1995-01-01

    Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time. Images Figure 1 Figure 2 PMID:8563510

  10. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  11. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  12. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  13. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer.

    PubMed

    Kim, Byung-Gyu; Li, Cuiling; Qiao, Wenhui; Mamura, Mizuko; Kasprzak, Barbara; Kasperczak, Barbara; Anver, Miriam; Wolfraim, Lawrence; Hong, Suntaek; Mushinski, Elizabeth; Potter, Michael; Kim, Seong-Jin; Fu, Xin-Yuan; Deng, Chuxia; Letterio, John J

    2006-06-22

    SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours.

  14. Focusing the management of rectal cancer

    PubMed Central

    Dbeis, Rachel; Smart, Neil J.

    2016-01-01

    Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction. PMID:28149883

  15. Laparoscopic rectopexy for solitary rectal ulcer syndrome without overt rectal prolapse: a case report and review of the literature.

    PubMed

    Menekse, Ebru; Ozdogan, Mehmet; Karateke, Faruk; Ozyazici, Sefa; Demirturk, Pelin; Kuvvetli, Adnan

    2014-02-20

    Solitary rectal ulcer syndrome is a rare clinical entity. Several treatment options has been described. However, there is no consensus yet on treatment algorithm and standard surgical procedure. Rectopexy is one of the surgical options and it is generally performed in patients with solitary rectal ulcer accompanied with overt prolapse. Various outcomes have been reported for rectopexy in the patients with occult prolapse or rectal intussusception. In the literature; outcomes of laparoscopic non-resection rectopexy procedure have been reported in the limited number of case or case series. No study has emphasized the outcomes of laparoscopic non-resection rectopexy procedure in the patients with solitary rectal ulcer without overt prolapse. In this report we aimed to present clinical outcomes of laparoscopic non-resection posterior suture rectopexy procedure in a 21-year-old female patient with solitary rectal ulcer without overt prolapse.

  16. Laparoscopic rectopexy for solitary rectal ulcer syndrome without overt rectal prolapse. A case report and review of the literature.

    PubMed

    Menekse, Ebru; Ozdogan, Mehmet; Karateke, Faruk; Ozyazici, Sefa; Demirturk, Pelin; Kuvvetli, Adnan

    2014-01-01

    Solitary rectal ulcer syndrome is a rare clinical entity. Several treatment options has been described. However, there is no consensus yet on treatment algorithm and standard surgical procedure. Rectopexy is one of the surgical options and it is generally performed in patients with solitary rectal ulcer accompanied with overt prolapse. Various outcomes have been reported for rectopexy in the patients with occult prolapse or rectal intussusception. In the literature; outcomes of laparoscopic non-resection rectopexy procedure have been reported in the limited number of case or case series. No study has emphasized the outcomes of laparoscopic non-resection rectopexy procedure in the patients with solitary rectal ulcer without overt prolapse. In this report we aimed to present clinical outcomes of laparoscopic non-resection posterior suture rectopexy procedure in a 21-year-old female patient with solitary rectal ulcer without overt prolapse.

  17. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

    PubMed

    Guerra-Pérez, Natalia; Aravantinou, Meropi; Veglia, Filippo; Goode, Diana; Truong, Rosaline; Derby, Nina; Blanchard, James; Grasperge, Brooke; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2016-01-01

    Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques), while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  18. Plague Masquerading as Gastrointestinal Illness

    PubMed Central

    Hull, Harry F.; Montes, Jean M.; Mann, Jonathan M.

    1986-01-01

    In clinical descriptions of human plague, fever and tender lymphadenitis are emphasized and gastrointestinal manifestations are rarely mentioned. A review of 71 human plague cases showed that gastrointestinal symptoms occurred commonly (57%). Vomiting (39%) was the most frequent symptom, with nausea (34%), diarrhea (28%) and abdominal pain (17%) occurring less often. Physicians treating patients who reside in or have recently visited plague-endemic areas should include plague in the differential diagnosis in the presence of gastrointestinal symptoms and fever. PMID:3788132

  19. Postembryonic development of rectal pads in bees (Hymenoptera, Apidae).

    PubMed

    Santos, Carolina Gonçalves; Neves, Clóvis Andrade; Zanuncio, José Cola; Serrão, José Eduardo

    2009-10-01

    The morphology and development of the digestive tract of insects has been extensively studied, but little attention has been given to the development of the rectal pads. These organs are responsible for absorption of water and salts. In insects where they occur, there are usually six ovoid rectal pads located in the medial-anterior portion of the rectum. The rectal pad has three types of cells: principal, basal, and junctional. The arrangement of these three cell types delimits an intrapapillary lumen. The aim of the current study is to describe the development of the rectal pads during postembryonic development of Melipona quadrifasciata anthidioides and Melipona scutellaris. Specimens were analyzed at the following developmental stages: white-, pink-, brown-, and black-eyed pupae, and adult workers. The development of the rectal pad begins as a thickening of the epithelium in white-eyed pupae at 54 hr. At this stage, there is neither a basal cell layer nor intrapapillary lumen. The basal layers begin to form in the pink-eyed pupa and are completely formed at the end of the development of the brown-eyed pupa. In the brown-eyed pupal stage, the intrapapillary lumen is formed and the junctional cells are positioned and completely differentiated. Necrotic and apoptotic cell death were detected along with cell proliferation in the whole rectum during pupal development, suggesting that the development of the rectal pads involves cell proliferation, death, and differentiation. The rectal pads originate only from the ectoderm.

  20. Microscopy detection of rectal gonorrhoea in asymptomatic men.

    PubMed

    Forni, J; Miles, K; Hamill, M

    2009-11-01

    This audit aimed to determine the usefulness of microscopy to detect presumptive rectal gonorrhoea (GC) infection in asymptomatic men. We retrospectively audited more than 400 male patients attending a London genitourinary medicine clinic from January 2005 to March 2007 who tested rectal culture positive for Neisseria gonorrhoeae and compared this with the microscopy detection rate. In total, 123/423 (29%) of culture positive samples were microscopy positive. Of those that tested microscopy negative (300/423), 64 (21%) were symptomatic and 236 (79%) asymptomatic. In addition, a time and motion study examined 81 rectal slides over a two-week period to identify microscopy reading time required to make a presumptive diagnosis of GC. Three slides were positive, resulting in six hours and 45 minutes to detect one positive sample. Given the low sensitivity for rectal microscopy coupled with the length of time required to obtain a presumptive positive rectal GC result, we believe rectal microscopy is no longer a cost-effective tool screening for asymptomatic men, and this report supports the BASHH guideline that it is not recommended in the management of asymptomatic rectal infection.

  1. Rectal and colon cancer: Not just a different anatomic site.

    PubMed

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs.

  2. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  3. Management of gastrointestinal haemorrhage

    PubMed Central

    Ghosh, S; Watts, D; Kinnear, M

    2002-01-01

    A variety of endoscopic haemostatic techniques have enabled major advances in the management of not only bleeding peptic ulcers and bleeding varices, but also in a variety of bleeding lesions in the small intestine and in the colon. Indeed, the development and widespread implementation of endoscopic haemostasis has been one of the most important developments in clinical gastroenterology in the past two decades. An increasingly ageing cohort of patients with multiple co-morbidity are being treated and therefore improving the outcome of gastrointestinal bleeding continues to pose major challenges. PMID:11796865

  4. Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

    PubMed

    Zhan, Han-Xiang; Zhou, Bin; Cheng, Yu-Gang; Xu, Jian-Wei; Wang, Lei; Zhang, Guang-Yong; Hu, San-Yuan

    2017-04-28

    Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease.

  5. BRAF exon 15 mutations in pediatric renal stromal tumors: prevalence in metanephric stromal tumors.

    PubMed

    Marsden, Lily; Jennings, Lawrence J; Gadd, Samantha; Yu, Min; Perlman, Elizabeth J; Cajaiba, Mariana M

    2017-02-01

    Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors. In this study, 17 MSTs, 22 congenital mesoblastic nephromas, and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by polymerase chain reaction amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11 (65%) of the 17 cases of MST, all corresponding to a thymidine-to-adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in most MSTs, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of metanephric neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating MSTs from other pediatric renal stromal tumors, particularly in limited samples.

  6. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  7. How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

    2013-11-01

    Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

  8. Perineal Rectosigmoidectomy (Altemeier Procedure) as Treatment of Strangulated Rectal Prolapse.

    PubMed

    Cernuda, Ricardo Baldonedo; Ángel, Janet Pagnozzi; Fernández, Nuria Truan; Sánchez-Farpón, José Herminio; Pérez, Jose Antonio Álvarez

    2016-12-01

    Incarceration of a rectal prolapse is an unusual entity that represents a surgical emergency. Even more rarely, it becomes strangulated, requiring emergency surgery. When surgery becomes inevitable, the choice of procedure varies. A 57-year-old man who presented with strangulated rectal prolapse is described. The patient underwent emergency perineal proctosigmoidectomy, the Altemeier operation, combined with diverting loop sigmoid colostomy. The postoperative course was uneventful. After a 6-month follow-up, there was no recurrence, but the patient continued with fecal incontinence. This case underlines the importance of the Altemeier procedure as treatment in the patient with a strangulated prolapsed rectal segment.

  9. Death by Disimpaction: A Bradycardic Arrest Secondary to Rectal Manipulation

    PubMed Central

    Shea, Cory M.

    2016-01-01

    Rectal examination and fecal disimpaction are common procedures performed in the Emergency Department on a daily basis. Here, we report a rare case of a patient suffering a cardiac arrest and ultimately death likely due to rectal manipulation. A 66-year-old male presented to the Emergency Department (ED) with a complaint of abdominal distention and constipation. A rectal exam was performed. During the examination the patient became apneic. On the cardiac monitor the patient was found to be in pulseless electrical activity with a bradycardic rate. Our recommendation would be to provide adequate analgesia and close patient monitoring of those undergoing this procedure especially patients with significant stool burdens. PMID:28116179

  10. Fournier gangrene: first manifestation of occult rectal cancer.

    PubMed

    Ruiz-Tovar, J; Córdoba, L; Devesa, J M

    2011-01-01

    Fournier gangrene is a necrotizing fasciitis of the genital and perineal region. Diverse factors predispose to Fournier gangrene, such as diabetes mellitus, ethylism, liver dysfunction, haematological disorders, obesity or recent regional instrumentation. Rectal tumours can also predispose to Fournier gangrene; most of the reported cases are perforated or unresectable colorectal tumours, but some cases of anorectal cancer diagnosed after recovery from Fournier gangrene have also been reported. In these cases, the presence of a rectal tumour at the time of, or prior to, diagnosis of Fournier gangrene could not be ruled out. We present three cases of rectal cancer whose first manifestation was as Fournier gangrene.

  11. [Strangled rectal prolapse in young adults: about a case and review of the literature].

    PubMed

    Bayar, Rached; Djebbi, Achref; Mzoughi, Zeineb; Talbi, Ghofrane; Gharbi, Lassaad; Arfa, Nafaa; Mestiri, Hafedh; Khalfallah, Mohamed Taher

    2016-01-01

    Rectal prolapse is a rectal static disorder which involves rectal wall intussusception inducing its externalization through the anus. It usually affects children and the elderly. Its occurrence in young adults is rare. Strangulated rectal prolapse is also a rare complication. We report the case of a 30-year old patient who underwent emergency surgery for strangulated rectal prolapse. Emergency perineal rectosigmoidectomy (Altemeier repair) was performed with simple outcome.

  12. Mesenchymal stromal cells for treatment of arthritis.

    PubMed

    Swart, J F; Wulffraat, N M

    2014-08-01

    Patients with refractory inflammatory arthritis can still respond favourable to autologous haematopoietic stem cell transplantation. However, this treatment has a high morbidity and even 5% mortality. Mesenchymal stromal cells (MSC), a subset of the non-haematopoietic stromal cells obtained from bone marrow, were found to have a strong immunosuppressive effect. MSC treatment is explored in many diseases like diabetes, SLE, MS and RA. This review covers all relevant literature regarding MSC treatment of inflammatory arthritis (RA and JIA). This review contains data of in vitro studies, animal studies and clinical studies. The following subjects will be discussed in detail: properties of MSC, presence of MSC in the joint, intra-articular versus intravenous route, autologous versus allogeneic, ideal source of MSC, distribution, transdifferentiation, engraftment, rejection, efficacy and toxicology. After reading this review the reader will be totally updated in this quickly evolving field of MSC therapy.

  13. Patient with eight metachronous gastrointestinal cancers thought to be hereditary nonpolyposis colorectal cancer (HNPCC).

    PubMed

    Yamasaki, Yasushi; Matsushima, Masashi; Tanaka, Hisae; Tajiri, Sakurako; Fukuda, Ryuki; Ozawa, Hideki; Takagi, Atsushi; Hirabayashi, Ken-ichi; Sadahiro, Sohtaro

    2010-01-01

    An 81-year-old woman presented with a chief complaint of swelling of both lower legs. She had a history of surgery for cancers of the stomach, rectum and colon. Among her immediate family members, her son had colon and rectal cancers, and her sister had ovarian cancer. After close examination the patient was diagnosed with small intestine cancer and ascending colon cancer. Gene mutation analyses did not reveal any mutations in DNA mismatch repair genes, but MSH-2 protein expression was lost only in the cancer lesions. Here, we report this rare case of eight metachronous gastrointestinal cancers thought to be HNPCC.

  14. Indium-111-labeled autologous leukocyte scanning in gastrointestinal graft versus host disease (GVHD)

    SciTech Connect

    Saverymuttu, S.H.; Peters, A.M.; O'Brien, C.; Chadwick, V.S.; Lavender, J.P.; Goldman, J.M.; Gordon-Smith, E.C.; Hodgson, H.J.

    1986-08-01

    The technique of scanning with indium-111 autologous leukocytes has been used to assess gastrointestinal graft-versus-host disease (GVHD) following allogenic marrow transplantation. In patients with active disease, abdominal scans showed extensive abnormal localization in the bowel, while in those whose disease was quiescent after responding to treatment, scans showed localized ileocecal involvement. Rectal histology showed excellent agreement with scanning in the diagnosis of GVHD, but in three of six cases with active disease underestimated disease severity. Indium-111 leukocyte scanning is a useful noninvasive technique for the diagnosis and assessment of gut GVHD.

  15. Rectal Douching and Implications for Rectal Microbicides among Populations Vulnerable to HIV in South America: A Qualitative Study

    PubMed Central

    Galea, Jerome T.; Kinsler, Janni J.; Imrie, John; Nureña, César R.; Sánchez, Jorge; Cunningham, William E.

    2014-01-01

    Objective While gel-formulated Rectal Microbicides (RM) are the first to enter clinical trials, rectal douching in preparation for anal intercourse is a common practise, thus RMs formulated as douches may be a convenient alternative to gels. Nonetheless, little is known about potential users’ thoughts regarding douche-formulated RMs or rectal douching practises, data needed to inform the advancement of douche-based RMs. This qualitative study examined thoughts regarding douches, their use as a RM and current douching practises among men who have sex with men and transgender women. Methods Ten focus groups and 36 in-depth interviews were conducted (N=140) to examine the overall acceptability of RM, of which one component focused on rectal douching. Focus groups and interviews were recorded, transcribed verbatim and coded; text relating to rectal douching was extracted and analysed. Sociodemographic information was collected using a self-administered questionnaire. Results Support for a douche-formulated RM centred on the possibility of combined pre-coital hygiene and HIV protection, and it was believed that a deeply-penetrating liquid douche would confer greater HIV protection than a gel. Drawbacks included rectal dryness; impracticality and portability issues; and, potential side effects. Non-commercial douching apparatus use was common and liquids used included detergents, vinegar, bleach, lemon juice and alcohol. Conclusions A douche-formulated RM while desirable and perceived as more effective than a gel-formulated RM also generated questions regarding practicality and side-effects. Of immediate concern were the non-commercial liquids already being used which likely damage rectal epithelia, potentially increasing HIV infection risk. Pre-coital rectal douching is common and a RM formulated as such is desirable, but education on rectal douching practices is needed now. PMID:23966338

  16. Radiation-Induced Thymidine Phosphorylase Upregulation in Rectal Cancer Is Mediated by Tumor-Associated Macrophages by Monocyte Chemoattractant Protein-1 From Cancer Cells

    SciTech Connect

    Kim, Tae-Dong; Li Ge; Song, Kyoung-Sub; Kim, Jin-Man; Kim, Jun-Sang; Kim, Jong-Seok; Yun, Eun-Jin; Park, Jong-Il; Park, Hae-Duck; Hwang, Byung-Doo; Lim, Kyu Yoon, Wan-Hee

    2009-03-01

    Purpose: The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. Methods and Materials: TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Results: Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Conclusions: Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

  17. Gastrointestinal Headache; a Narrative Review

    PubMed Central

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-01-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder. PMID:27800536

  18. Gastrointestinal Headache; a Narrative Review.

    PubMed

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-11-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder.

  19. Sclerosing stromal tumor of the ovary in a premenarchal female.

    PubMed

    Fefferman, Nancy R; Pinkney, Lynne P; Rivera, Rafael; Popiolek, Dorota; Hummel-Levine, Pascale; Cosme, Jaqueline

    2003-01-01

    Sclerosing stromal tumor (SST) is a rare benign ovarian neoplasm of stromal origin with less than 100 cases reported in the literature. Unlike the other stromal tumors, thecomas and fibromas, which tend to occur in the fifth and sixth decades, sclerosing stromal tumors predominantly affect females in the second and third decades. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound findings have been described, but have not been reported previously in the pediatric literature. We present a case of SST of the ovary in a 10-year-old premenarchal female, the youngest patient to our knowledge reported in the literature, and describe the ultrasound and CT findings with pathologic correlation.

  20. Stromal Effects on Mammary Gland Development and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  1. Tailoring treatment of rectal adenocarcinoma: immunohistochemistry for predictive biomarkers.

    PubMed

    Kapur, Payal

    2011-04-01

    Over the past couple of decades, multimodality treatment for the management of resectable rectal cancer has substantially improved the outcome of affected patients. However, the broad and unpredictable response to tumor of patients with rectal cancer treated with preoperative chemoradiotherapeutic interventions shows that our understanding of the molecular events leading to radioresistance in patients affected with this malignancy remains sparse. Multiple attempts by individual molecular markers in gene array and tissue microarray studies have emerged with the goal of identifying predictors of a response to chemoradiation in patients with rectal cancer. In this report, we discuss the status of the markers currently available in an attempt to tailor specific targeted therapies for rectal cancer in the neoadjuvant setting.

  2. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  3. MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing.

    PubMed

    Gyvyte, Ugne; Juzenas, Simonas; Salteniene, Violeta; Kupcinskas, Juozas; Poskiene, Lina; Kucinskas, Laimutis; Jarmalaite, Sonata; Stuopelyte, Kristina; Steponaitiene, Ruta; Hemmrich-Stanisak, Georg; Hübenthal, Matthias; Link, Alexander; Franke, Sabine; Franke, Andre; Pangonyte, Dalia; Lesauskaite, Vaiva; Kupcinskas, Limas; Skieceviciene, Jurgita

    2017-03-29

    Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways. Further, we used an integrated analysis of miRNA-mRNA correlations for KIT and PDGFRA target genes and found a significant correlation between all of the enriched miRNAs and their target gene KIT. Results of the phenotype analysis showed miR-509-3p to be up-regulated in epithelioid and mixed cell types compared to spindle type, whereas miR-215-5p showed negative correlation with risk grade of GIST. These data reveal a detailed miRNA profile of GIST and highlight new candidates that may be important in the development of malignant disease.

  4. Study on the Evolution of Genes Mutation Related With Gastrointestinal Stromal Tumors

    ClinicalTrials.gov

    2012-01-05

    Full Gene Sequences of c-KIT、PDGFRA and DOG1 Are Analyzed With the Screening-sequencing Approach; Investigate the Characteristics and Variations Associated With the Different Gene Mutations of c-KIT、PDGFRA and DOG1 in GIST Patients

  5. Prognostic values of DLK1 for surgery and imatinib mesylate adjuvant therapy in gastrointestinal stromal tumors

    PubMed Central

    Xu, Jia; Wang, Ming; Zhang, Zizhen; Zhao, Wenyi; Wang, Chaojie; Tu, Lin; Zhang, Yeqian; Cao, Hui

    2016-01-01

    The Delta-like 1 homolog (DLK1) gene is a paternal imprinting gene located on human chromosome 14q32, a site associated with frequent chromosomal mutations in GIST. The expression level of DLK1 is closely associated with the outcome of tumours. However, no study has reported the DLK1 expression in GIST. Here, we demonstrated that DLK1 showed low expression in GIST patients with low risk according to the modified National Institute of Health (NIH) criteria. With increasing tumour risk level, DLK1 gene and protein expression levels gradually increased. In the test cohort, tissue microarray data showed that DLK1 protein expression was significantly associated with tumour size, mitotic figure count, NIH risk level, and Ki67 expression. In terms of either disease-free survival (DFS) or overall survival (OS), the long-term outcome was significantly better in DLK1-negative patients than in DLK1-positive patients. Univariate and multivariate analyses suggested that DLK1 expression was an independent risk factor influencing tumour DFS. Additionally, for intermediate/high-risk GIST patients received postoperative IM adjuvant therapy, Kaplan-Meier analysis showed that IM adjuvant therapy was associated with a better outcome in DLK1-negative patients than in DLK1-positive patients. All of the above results were verified in the validation cohort. Taken together, DLK1 is a promising prognostic biomarker for GISTs that may help to predict surgical outcomes and guide adjuvant IM therapy. PMID:27904782

  6. Combined-modality therapy for rectal cancer using irinotecan.

    PubMed

    Minsky, Bruce D

    2002-05-01

    Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.

  7. A crunching colon: rectal bezoar caused by pumpkin seed consumption.

    PubMed

    Manne, Janaki R; Rangu, Venu M; Motapothula, Uma Maheswara R; Hall, Matthew C

    2012-05-01

    Rectal seed bezoars are an uncommon cause of fecal impaction, particularly in the United States. Although the literature has reported several cases of phytobezoars composed of various types of seeds, bezoars formed of pumpkin seeds have rarely been reported. We report a case of a man, aged 62 years, with a rectal bezoar composed of pumpkin seeds with complications necessitating extensive treatment, including manual disimpaction and colonoscopy.

  8. Changes in mouse gastrointestinal microbial ecology with ingestion of kale.

    PubMed

    Uyeno, Y; Katayama, S; Nakamura, S

    2014-09-01

    Kale, a cultivar of Brassica oleracea, has attracted a great deal of attention because of its health-promoting effects, which are thought to be exerted through modulation of the intestinal microbiota. The present study was performed to investigate the effects of kale ingestion on the gastrointestinal microbial ecology of mice. 21 male C57BL/6J mice were divided into three groups and housed in a specific pathogen-free facility. The animals were fed either a control diet or experimental diets supplemented with different commercial kale products for 12 weeks. Contents of the caecum and colon of the mice were processed for the determination of active bacterial populations by a bacterial rRNA-based quantification method and short-chain fatty acids by HPLC. rRNAs of Bacteroides-Prevotella, the Clostridium coccoides-Eubacterium rectale group, and Clostridium leptum subgroup constituted the major fraction of microbiota regardless of the composition of the diet. The ratio of Firmicutes to Bacteroidetes was higher in the colon samples of one of the kale diet groups than in the control. The colonic butyrate level was also higher with the kale-supplemented diet. Overall, the ingestion of kale tended to either increase or decrease the activity of specific bacterial groups in the mouse gastrointestinal tract, however, the effect might vary depending on the nutritional composition.

  9. Extragastrointestinal Stromal Tumor (EGIST) in the abdominal wall: Case report and literature review

    PubMed Central

    Alkhatib, Loiy; Albtoush, Omar; Bataineh, Nesreen; Gharaibeh, Kamal; Matalka, Ismail; Tokuda, Yasuharu

    2011-01-01

    INTRODUCTION Gastro Intestinal Stromal Tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract (GI). GIST that arises primarily outside the GI tract is termed Extragastrointestinal Stromal Tumor (EGIST). To the best of our knowledge, few cases of EGIST in the abdominal wall were reported. PRESENTATION OF CASE We present a rare case of EGIST in the abdominal wall of a 57 year-old female patient. The asymptomatic tumor was located in the superior aspect of the left rectus abdominis muscle, measured 5.4 × cm 5.3 × cm 6.9 cm and was well circumscribed. Histological examination showed an epithelioid cell morphology. The mitotic count was 7/50 HPFs. Immunohistochemistry showed diffuse strong CD117 positivity, focal positivity for S100. The tumor was excised and the margins were free of malignancy. The patient was doing well postoperatively and was discharged on STI-571 regimen. DISCUSSION Although GIST is the most common mesenchymal tumor of the gastrointestinal tract, a case with EGIST in the abdominal wall is rare. Positive immunohistochemical staining for CD117 is a defining feature of GISTs. A great percentage of EGISTs represent a metastasis from a primary GIST. In our case, the clinical and diagnostic work-up have been proved it to be an EGIST. CONCLUSION The existing data on EGIST is insufficient to make a final conclusion regarding the malignant potential and clinicopathological factors of EGISTs that determine patient prognosis. Thus a follow-up for a long period is required. EGISTs should be kept in mind in the differential diagnosis for patients presenting with solid mass of the abdominal wall. PMID:22096744

  10. Hereditary gastrointestinal cancer.

    PubMed

    Hata, Keisuke; Yamamoto, Yoko; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kishikawa, Junko; Nagai, Yuzo; Anzai, Hiroyuki; Shinagawa, Takahide; Arakawa, Keiichi; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2016-10-01

    Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.

  11. Dysbiosis in gastrointestinal disorders.

    PubMed

    Chang, Christopher; Lin, Henry

    2016-02-01

    The recent development of advanced sequencing techniques has revealed the complexity and diverse functions of the gut microbiota. Furthermore, alterations in the composition or balance of the intestinal microbiota, or dysbiosis, are associated with many gastrointestinal diseases. The looming question is whether dysbiosis is a cause or effect of these diseases. In this review, we will evaluate the contribution of intestinal microbiota in obesity, fatty liver, inflammatory bowel disease, and irritable bowel syndrome. Promising results from microbiota or metabolite transfer experiments in animals suggest the microbiota may be sufficient to reproduce disease features in the appropriate host in certain disorders. Less compelling causal associations may reflect complex, multi-factorial disease pathogenesis, in which dysbiosis is a necessary condition. Understanding the contributions of the microbiota in GI diseases should offer novel insight into disease pathophysiology and deliver new treatment strategies such as therapeutic manipulation of the microbiota.

  12. [Gastrointestinal dysmotility in children].

    PubMed

    Fluge, G; Olafsdottir, E

    2001-03-20

    Motility disorders were previously impossible to penetrate, but new technics have made it possible to investigate these disorders. An overview of neurophysiological functions of the gastrointestinal tract is given, and various conditions representing primary and secondary motility disorders are discussed. Diagnostic procedures and treatment options are presented. The clinical picture of such disorders is demonstrated by two cases. A girl born in 1995, having megacystis microcolon hypoperistalsis syndrome was the first Norwegian individual to have an intestinal transplantation, which was performed in London, UK. A girl with hypoganglionosis is also reported. Since May 1998, manometry of the oesophagus was performed in 44 children, and pathological findings were demonstrated in 18 of these patients. The motoric activity of the stomach was investigated in 17 patients using two-dimensional ultrasound and electrogastrography pre- and post-prandially. Disturbed function was found in nine of these children. Anorectal manometry was performed in 147 individuals, and Hirschsprung's disease was diagnosed in four.

  13. Gastrointestinal infections in children.

    PubMed

    Mönkemüller, K E; Wilcox, C M

    2001-01-01

    Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

  14. Disorders of gastrointestinal hypomotility

    PubMed Central

    Bielefeldt, Klaus; Tuteja, Ashok; Nusrat, Salman

    2016-01-01

    Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases. PMID:27583135

  15. Excretory transport of xenobiotics by dogfish shark rectal gland tubules.

    PubMed

    Miller, D S; Masereeuw, R; Henson, J; Karnaky, K J

    1998-09-01

    Marine elasmobranch rectal gland is a specialized, osmoregulatory organ composed of numerous blind-ended, branched tubules emptying into a central duct. To date, NaCl excretion has been its only described function. Here we use isolated rectal gland tubule fragments from dogfish shark (Squalus acanthias), fluorescent xenobiotics, and confocal microscopy to describe a second function, xenobiotic excretion. Isolated rectal gland tubules rapidly transported the fluorescent organic anion sulforhodamine 101 from bath to lumen. Luminal accumulation was concentrative, saturable, and inhibited by cyclosporin A (CSA), chlorodinitrobenzene, leukotriene C4, and KCN. Inhibitors of renal organic anion transport (probenecid, p-aminohippurate), organic cation transport (tetraethylammonium and verapamil), and P-glycoprotein (verapamil) were without effect. Cellular accumulation of sulforhodamine 101 was not concentrative, saturable, or inhibitable. Rectal gland tubules did not secrete fluorescein, daunomycin, or a fluorescent CSA derivative. Finally, frozen rectal gland sections stained with an antibody to a hepatic canalicular multispecific organic anion transporter (cMOAT or MRP2) showed heavy and specific staining on the luminal membrane of the epithelial cells. We conclude that rectal gland is capable of active and specific excretion of xenobiotics and that such transport is mediated by a shark analog of MRP2, an ATP-driven xenobiotic transporter, but not by P-glycoprotein.

  16. Laboratory procedures for the diagnosis of gastrointestinal tract diseases of dogs and cats.

    PubMed

    Matz, M E; Guilford, W G

    2003-12-01

    An increasing number of laboratory tests are available for diagnosis of gastrointestinal tract diseases in dogs and cats. Use of these tests can lead to more accurate and rapid diagnoses. This review discusses laboratory tests, both new and old, and the role they currently play in the evaluation of animals presented with gastrointestinal problems. A minimum database helps assess the severity of the disorder, detect extra-gastrointestinal causes of problems and assists in formulating diagnostic and therapeutic plans. Faecal examination remains one of the most important diagnostic procedures in the investigation of gastrointestinal problems. Zinc sulphate faecal flotation is an excellent routine screening technique for helminth and protozoal infections, including giardiasis. Rectal cytology can assist in the diagnosis of large bowel disorders. Interpretation of faecal immunodiagnostic tests is hampered by insufficient knowledge of test sensitivities and specificities. Routine faecal cultures are not warranted and faecal occult blood tests are rarely indicated. Serum tests for gastric inflammation are now under development. The serum trypsin-like immunoreactivity test remains the gold standard technique for the diagnosis of exocrine pancreatic insufficiency. Breath hydrogen tests can be helpful in assessing the functional relevance of mild abnormalities in small-bowel biopsy specimens. Subnormal concentrations of serum cobalamin appear to be more specific indicators of gastrointestinal disease in cats than in dogs. Tests for small intestinal bacterial overgrowth remain controversial and assessment of gastrointestinal permeability has yet to prove its value in the diagnostic assessment of companion animals with gastrointestinal problems. Faecal alpha1-protease inhibitor shows promise for the diagnosis of protein-losing enteropathy.

  17. Gastrointestinal colonization with ESBL-producing Klebsiella in preterm babies--is vancomycin to blame?

    PubMed

    Ofek-Shlomai, N; Benenson, S; Ergaz, Z; Peleg, O; Braunstein, R; Bar-Oz, B

    2012-04-01

    In this study, we examine the possible association between treatment with vancomycin and colonization with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella in our neonatal intensive care unit (NICU). Variables compared between newborns which developed rectal colonization and those who did not include: gestational age, birth weight, gender, and total length of hospital stay until positive stool culture or discharge, treatment with vancomycin, and positive blood culture for coagulase-negative Staphylococcus. We found that lower birth weight, younger gestational age, and treatment with vancomycin were statistically significant risk factors for gastrointestinal colonization with ESBL-producing Klebsiella. When applying a multivariate model, treatment with vancomycin, both for a full 10-day course and for a short 3-day empirical treatment, remained statistically significant. Treatment with vancomycin is a risk factor for gastrointestinal colonization with ESBL-producing Klebsiella in premature babies.

  18. The accuracy of endorectal ultrasonography in rectal cancer staging

    PubMed Central

    COTE, ADRIAN; GRAUR, FLORIN; LEBOVICI, ANDREI; MOIS, EMIL; AL HAJJAR, NADIM; MARE, CODRUTA; BADEA, RADU; IANCU, CORNEL

    2015-01-01

    Background and aims The incidence of rectal cancer in the European Union is about 35% of the total colorectal cancer incidence. Staging rectal cancer is important for planning treatment. It is essential for the management of rectal cancer to have adequate preoperative imaging, because accurate staging can influence the therapeutic strategy, type of resection, and candidacy for neoadjuvant therapy. The aim of this work is to evaluate the accuracy of endorectal ultrasound (ERUS) in rectal cancer staging. Methods A retrospective study was performed to assess the accuracy of ERUS by analyzing patients discharged from Regional Institute of Gastroenterology and Hepatology (IRGH) Cluj-Napoca, Romania, diagnosed with rectal cancer between 01 January 2011 and 31 December 2013. Patients who were preoperatively staged by other imaging methods and those who had ERUS performed in another service were excluded from the analysis. As inclusion criteria remained ERUS performed for patients with rectal cancer in IRGH Cluj-Napoca where they were also operated. We analyzed preoperative T stage obtained by ERUS and it was compared with the histopathology findings. Results The number of patients discharged with a diagnosis of rectal cancer were 200 (operated – 157) in 2011, 193 (operated – 151) in 2012, and 198 (operated – 142) in 2013. We analyzed a total of 51 cases diagnosed with rectal cancer who performed ERUS in IRGH Cluj-Napoca. The results according to the T stage obtained by ERUS and histopathology test were: Under-stage T2= 25.0%, T3=7.9% of cases; Over-stage T2=25.0%, T3=31.6% and T4=60.0% of cases. Less than 20% of patients underwent preoperative radio-chemotherapy. Conclusions ERUS is a method of staging rectal cancer which is human dependent. ERUS is less accurate for T staging of stenotic tumours, but the accuracy may still be within acceptable limits. Surgeons use ERUS to adopt a treatment protocol, knowing the risk of under-staging and over-staging of this method

  19. An Air-Liquid Interface Culture System for 3D Organoid Culture of Diverse Primary Gastrointestinal Tissues.

    PubMed

    Li, Xingnan; Ootani, Akifumi; Kuo, Calvin

    2016-01-01

    Conventional in vitro analysis of gastrointestinal epithelium usually relies on two-dimensional (2D) culture of epithelial cell lines as monolayer on impermeable surfaces. However, the lack of context of differentiation and tissue architecture in 2D culture can hinder the faithful recapitulation of the phenotypic and morphological characteristics of native epithelium. Here, we describe a robust long-term three-dimensional (3D) culture methodology for gastrointestinal culture, which incorporates both epithelial and mesenchymal/stromal components into a collagen-based air-liquid interface 3D culture system. This system allows vigorously expansion of primary gastrointestinal epithelium for over 60 days as organoids with both proliferation and multilineage differentiation, indicating successful long-term intestinal culture within a microenvironment accurately recapitulating the stem cell niche.

  20. What Are the Key Statistics about Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... About Gastrointestinal Carcinoid Tumors What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? Although the exact number ... a Gastrointestinal Carcinoid Tumor? What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? What’s New in Gastrointestinal ...

  1. Prevalence of lower gastrointestinal symptoms and associated consultation behaviour in a British elderly population determined by face-to-face interview.

    PubMed Central

    Chaplin, A; Curless, R; Thomson, R; Barton, R

    2000-01-01

    BACKGROUND: The incidence of organic lower gastrointestinal disease increases with age. However, the prevalence of lower gastrointestinal symptoms in a British elderly population is unclear, with previous epidemiological studies focusing on younger populations. Furthermore, there is little information about consultation behaviour associated with lower gastrointestinal symptoms. AIM: To determine the prevalence of lower gastrointestinal symptoms reported by randomly selected, elderly community subjects. METHODS: An age- and sex-stratified random sample of patients aged 65 years and over was drawn from a general practice register (n = 842). Those who had not refused to participate in an initial postal survey were invited to participate in a semi-structured physician interview at their own home to assess lower gastrointestinal symptomatology (n = 745). Non-participation bias and service use of all subjects were assessed from practice records. RESULTS: Five hundred and ninety-six (71%) patients were interviewed. Fifty-seven per cent of all participants had at least one lower gastrointestinal symptom. Individual symptoms and symptom complexes were common, affecting up to 32% of subjects. Only 24% of subjects with lower gastrointestinal symptoms consulted their general practitioner (GP) with such symptoms in the previous year. As few as 31% of subjects with new onset of the significant symptoms of rectal bleeding, abdominal pain, and a change in bowel habit consulted their GP. CONCLUSION: Lower gastrointestinal symptoms are common in a British elderly population and an important reason for GP consultation. PMID:11127169

  2. Autistic disorder and gastrointestinal disease.

    PubMed

    Horvath, Karoly; Perman, Jay A

    2002-10-01

    Autistic disorder is a pervasive developmental disorder manifested in the first 3 years of life by dysfunction in social interaction and communication. Many efforts have been made to explore the biologic basis of this disorder, but the etiology remains unknown. Recent publications describing upper gastrointestinal abnormalities and ileocolitis have focused attention on gastrointestinal function and morphology in these children. High prevalence of histologic abnormalities in the esophagus, stomach, small intestine and colon, and dysfunction of liver conjugation capacity and intestinal permeability were reported. Three surveys conducted in the United States described high prevalence of gastrointestinal symptoms in children with autistic disorder. Treatment of the digestive problems may have positive effects on their behavior.

  3. Phase II Study of Preoperative Helical Tomotherapy With a Simultaneous Integrated Boost for Rectal Cancer

    SciTech Connect

    Engels, Benedikt; Tournel, Koen; Everaert, Hendrik; Hoorens, Anne; Sermeus, Alexandra; Christian, Nicolas; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2012-05-01

    Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade {>=}3 acute toxicities occurred. With a median follow-up of 32 months, Grade {>=}3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

  4. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  5. Synchronous rectal and gastric cancer in a fighter pilot: aeromedical concerns.

    PubMed

    Gu, Guo-Li; Wei, Xue-Ming; Xu, Xian-Rong; Li, De-Chang; Wang, Shi-Lin; Gu, Jin

    2013-06-01

    Synchronous cancer of the stomach and rectum is very rare. In a special population of pilots, especially fighter pilots, synchronous rectal and gastric cancer is much more uncommon. We herein report a case of synchronous carcinoma of the rectum and stomach. The patient was a 44-year-old male fighter pilot who complained with bloody stool and altered bowel habits. He was diagnosed with hereditary nonpolyposis colorectal cancer with a definite family history, and subsequently he underwent simultaneous low anterior resection and distal gastrectomy with D2 lymphadenectomy. Postoperative pathologic assessment showed a poorly differentiated gastric adenocarcinoma with signet ring cell components (pT2N1M0; stage IIb) and a moderately differentiated rectal adenocarcinoma with myxoid components (pT3N0M0; stage IIa). Both tumors showed positive expression of p53, Ki-67, VEGF, carcinoembryonic antigen, MRP, TS, P-gp, and TopoII, and negative expression of c-erbB2, CD34, CD31, D2-40, S-100, FVIII, MLH1, MSH2, and MSH6 oncoproteins. Six cycles of XELOX chemotherapy and 50 Gy/25 f radiotherapy were delivered postoperatively. Now, he has returned to his work under medical observation for about 6 months. From this patient's diagnosis and treatment, we think that the gene screening should be used in pilot selection. According to the result of gene screening, we can give pertinence examinations to the target organ of genes. It is very necessary for pilots to keep keen vigilance at gastrointestinal tumors because they have to face many high-risk factors in working. As to pilots, the selection of operation should be individualized.

  6. Epithelial and Stromal Spectral Imaging for Rapid Surgical Margin Analysis

    DTIC Science & Technology

    2012-03-01

    for key diagnostic classes. The optical system samples mesoscopic tissue volumes; therefore, microscopic segmentation of glandular , stromal and...heterogeneous, but imaging-pathology correlates revealed that this variation had a spatial pattern that reflected the organization of glandular structures...characterized by marked expansion of glandular units by neo-plastic cells, compressing (but not invading) the surrounding stromal environment

  7. Gastrointestinal tract spindle cell lesions--just like real estate, it's all about location.

    PubMed

    Voltaggio, Lysandra; Montgomery, Elizabeth A

    2015-01-01

    Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

  8. Stromal cells can contribute oncogenic signals

    NASA Technical Reports Server (NTRS)

    Tlsty, T. D.

    2001-01-01

    The majority of studies of neoplastic transformation have focused attention on events that occur within transformed cells. These cell autonomous events result in the disruption of molecular pathways that regulate basic activities of the cells such as proliferation, death, movement and genomic integrity. Other studies have addressed the microenvironment of tumor cells and documented its importance in supporting tumor progression. Recent work has begun to expand on these initial studies of tumor microenvironment and now provide novel insights into the possible initiation and progression of malignant cells. This review will address the transforming effect of stromal cells on epithelial components. Copyright 2001 Academic Press.

  9. Schwann cells induce neuronal differentiation of bone marrow stromal cells.

    PubMed

    Zurita, Mercedes; Vaquero, Jesús; Oya, Santiago; Miguel, Miriam

    2005-04-04

    Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

  10. Stromal networking: cellular connections in the germinal centre.

    PubMed

    Denton, Alice E; Linterman, Michelle A

    2017-03-17

    Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ. Further, distinct populations of stromal cells underpin the delicate spatial organization of immune cells within the germinal centre. Because of this, the interactions between immune cells and stromal cells in secondary lymphoid organs are fundamental to the germinal centre response. Herein we review how this unique relationship leads to effective germinal centre responses.

  11. The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.

    PubMed

    Woodby, B; Scott, M; Bodily, J

    2016-01-01

    Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs, or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology, focusing on stromal fibroblasts, immune cells, and endothelial cells. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

  12. Giant fibroepithelial stromal polyp of the vulva: largest case reported

    PubMed Central

    2013-01-01

    Background Fibroepithelial stromal polyps are site-specific mesenchymal lesions that are commonly found in the vulvovaginal region in premenopausal females. These polyps usually are less than 5 cm in diameter and are most commonly identified during routine gynecological examination. Although the stromal polyp is benign, its differential diagnosis includes some malignant vulva lesions making it critical to ensure that an accurate pathologic diagnosis is made. Case We present a case of a 21 year old female with a giant fibroepithelial stromal polyp of the vulva. Upon review of the literature this is the largest reported fibroepithelial stromal polyp to date. Conclusion Fibroepithelial stromal polyps can grow as large as 390 grams and can be 18.5-cm in diameter. Microscopic evaluation of the polyp is critical in the exclusion of malignancy with this diagnosis. PMID:23842282

  13. Outcome of young patients with rectal adenocarcinoma

    PubMed Central

    Salcedo-Hernández, Rosa A.; Ruiz-García, Erika B.; León-Takahashi, Alberto M.; García-Pérez, Leticia

    2017-01-01

    Background There is an increase in the incidence of rectal carcinoma (RC) in young patients. Methods We analyzed 175 patients with sporadic RC which were divided in two groups according their age: 24 patients ≤40 years and 151 patients >40 years and the two groups were compared in order to determine if the outcomes (especially overall 5-year survival) were different. Results Overall 5-year survival was similar between groups (67.1% for patients over 40 years and 70.4% for those under 40 years, P=0.803). The only differences found were in some clinicopathologic features: patients <40 years showed more dissected lymph nodes (LNs) (21 vs. 15, P=0.035) and more LN metastasis (54.2% vs. 39.1%, P=0.048). In multivariate analysis factors associated with worse survival were incomplete resection and no use of neoadjuvant therapy. Age did not demonstrate prognostic value (P=0.077). Conclusions RC in people ≤40 years demonstrated greater number of LN harvested and LN metastases but oncologic outcomes, especially 5-year overall survival, were similar between groups. PMID:28280614

  14. [Peri-operative treatments for rectal cancer].

    PubMed

    Gérard, Jean-Pierre; Doyen, Jerome; Bénézery, Karen; Borens, Bruno; Hannoun-Levi, Jean-Michel; François, Éric

    2015-06-01

    Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with concurrent chemotherapy (capecitabine) according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes possible to escalate safely the dose of irradiation using contact X-ray brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant chemotherapy may be given in case of pejorative pathological findings but its benefit is not yet proven in contrast with colon cancer. Local recurrences are becoming unusual as is permanent APE surgery with permanent stoma. To reduce the risk of distant metastasis clinical trials are testing first line chemotherapy in T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve organ preservation. Intensification of CAP 50 either with more chemotherapy or radiation dose escalation using contact X-ray aim at achieving a clinical complete response followed by local excision or close surveillance.

  15. [Quality standards in rectal cancer surgery].

    PubMed

    Pera, M; Pascual, M

    2005-01-01

    The results of surgery for rectal cancer have classically been measured through indicators such as morbidity, mortality, and length of hospital stay. In the last few years other parameters have been included that evaluate healthcare quality such as the functional results of the surgical technique employed and quality of life. Total resection of the mesorectum, performed by experienced surgeons, is the surgical technique of choice. Currently, the sphincter can be preserved in 70% of patients. Anastomotic dehiscence after anterior resection of the rectum is the most serious complication and the most important risk factor is the height of the anastomosis. The overall dehiscence rate should be less than 15% and operative mortality should be between 2% and 3%. The colonic reservoir improves functional outcome and consequently it is the procedure of choice to reconstruct transit after low anterior resection. Local recurrence should be less than 10% and 5-year survival should be between 70% and 80%. In general, quality of life is better after anterior resection of the rectum than after abdominoperineal amputation, despite the functional deterioration presented by some patients.

  16. Rectal suppository: commonsense and mode of insertion.

    PubMed

    Abd-el-Maeboud, K H; el-Naggar, T; el-Hawi, E M; Mahmoud, S A; Abd-el-Hay, S

    1991-09-28

    Rectal suppository is a well-known form of medication and its use is increasing. The commonest shape is one with an apex (pointed end) tapering to a base (blunt end). Because of a general lack of information about mode of insertion, we asked 360 lay subjects (Egyptians and non-Egyptians) and 260 medical personnel (physicians, pharmacists, and nurses) by questionnaire which end they inserted foremost. Apart from 2 individuals, all subjects suggested insertion with the apex foremost. Commonsense was the most frequent basis for this practice (86.9% of lay subjects and 84.6% of medical personnel) followed by information from a relative, a friend, or medical personnel, or from study at medical school. Suppository insertion with the base or apex foremost was compared in 100 subjects (60 adults, 40 infants and children). Retention with the former method was more easily achieved in 98% of the cases, with no need to introduce a finger in the anal canal (1% vs 83%), and lower expulsion rate (0% vs 3%). The designer of the "torpedo-shaped" suppository suggested its insertion with apex foremost. Our data suggest that a suppository is better inserted with the base foremost. Reversed vermicular contractions or pressure gradient of the anal canal might press it inwards.

  17. 'Objective' assessment of rectal sensation: a novel approach.

    PubMed

    Shafik, Ahmed; El-Sibai, Olfat; Shafik, Ali A; Ahmed, Ismail

    2004-01-01

    Rectal sensation is used as an investigative tool in the diagnosis of anorectal pathology. However, the data obtained are subjective depending on the patient's perception of the sensation. We investigated the hypothesis that sympathetic skin response (SSR) can be used as a tool for objective assessment of the rectal sensation. The SSR was recorded in 24 healthy volunteers (age 37.2 years, 14 men) using a surface electrode applied to the skin of the palmar surface of the subject's hand and a reference electrode to the dorsum of the same hand. The EMG activity of the pelvic floor muscles was registered by a surface electrode fixed to the perineal skin. The subject was asked before and after individual anesthetization of the rectum and palm to report the first rectal and urge sensations during balloon filling of the rectum in increments of 10 ml of saline. Low volume rectal distension effected no sympathetic skin or pelvic floor responses, while larger volumes produced the response. The skin and pelvic floor responses occurred with every rectal sensation and corresponded with the volunteers' subjective perception. Urge suppression was associated with synchronous decrease of skin and pelvic floor responses which disappeared on balloon expulsion. Rectal balloon distension, 20 minutes after individual anesthetization of the rectum or palm produced no palm skin response, which returned however 3 hours later. A novel approach which can objectively define subjective perceptions arising from the rectum has been identified. Rectal sensations produce coordinated sympathetic skin response and pelvic floor activity which seem to be mediated through a reflex which we term the "recto-palmar reflex". Further studies are required to investigate the role of this reflex in defection and sympathetic disorders.

  18. Hedgehog signaling and gastrointestinal cancer

    PubMed Central

    Saqui-Salces, Milena; Merchant, Juanita L.

    2017-01-01

    Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De-regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID:20307590

  19. Epigenetic mechanisms and gastrointestinal development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review considers the hypothesis that nutrition during infancy affects developmental epigenetics in the gut, causing metabolic imprinting of gastrointestinal (GI) structure and function. Fundamentals of epigenetic gene regulation are reviewed, with an emphasis on the epigenetic mechanism of DNA ...

  20. The Gastrointestinal Microbiome

    PubMed Central

    Engen, Phillip A.; Green, Stefan J.; Voigt, Robin M.; Forsyth, Christopher B.; Keshavarzian, Ali

    2015-01-01

    The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption on the microbiota in the gastrointestinal tract (GIT). Although data are limited in humans, studies highlight the importance of changes in the intestinal microbiota in alcohol-related disorders. Alcohol-induced changes in the GIT microbiota composition and metabolic function may contribute to the well-established link between alcohol-induced oxidative stress, intestinal hyperpermeability to luminal bacterial products, and the subsequent development of alcoholic liver disease (ALD), as well as other diseases. In addition, clinical and preclinical data suggest that alcohol-related disorders are associated with quantitative and qualitative dysbiotic changes in the intestinal microbiota and may be associated with increased GIT inflammation, intestinal hyperpermeability resulting in endotoxemia, systemic inflammation, and tissue damage/organ pathologies including ALD. Thus, gut-directed interventions, such as probiotic and synbiotic modulation of the intestinal microbiota, should be considered and evaluated for prevention and treatment of alcohol-associated pathologies. PMID:26695747

  1. Gastrointestinal mucormycosis in immunocompromised hosts.

    PubMed

    Dioverti, M Veronica; Cawcutt, Kelly A; Abidi, Maheen; Sohail, M Rizwan; Walker, Randall C; Osmon, Douglas R

    2015-12-01

    Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non-specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.

  2. Lipomas of the gastrointestinal system.

    PubMed

    Dolai, Matilda; Andrejić, Bojana; Ivanov, Dejan

    2012-01-01

    Lipomas are rare benign tumors in the gastrointestinal system. Within the gastrointestinal system, 65% of the lipomas are located in the colon (sigmoid part of the colon or rectum) and rarely in the stomach and esophagus. The paper presents two gastrointestinal lipomas. First is the case of lipoma of the sigmoid colon and the other one is gastric lipoma. In both cases the material was sent for histopathological analysis due to suspicion of malignancy of the lesions. In both cases, the histopathologic analysis showed tumor made of mature adipocytes, localized in the submucosa both of the stomach and intestine. Hypercellularity and/or atypia of the cell was found in neither case. Lipomas are shown because of its atypical localization and clinically suspicious malignancy in the stomach and sigmoid colon. These cases show that the applied methods of preoperative diagnosis of tumors in the gastrointestinal system are not sufficient to determine the origin and biological behavior of tumors. Histopathological diagnosis provides a correct insight into the nature of tumors and determine the course of treatment. This paper presents a rare localization of lipomas in the gastrointestinal system. The preoperative diagnosis of lesions in the gastrointestinal system may not be sufficient to determine the origin and biological behavior of the lesions, hence the histopathological diagnosis gives an accurate insight into the nature of the change, preventing the possibility of further aggressive therapy.

  3. COX2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

    PubMed Central

    Dawsey, Sonja P.; Roth, Mark J.; Adams, Lisa; Hu, Nan; Wang, Quan-Hong; Taylor, Philip R.; Woodson, Karen

    2008-01-01

    Background Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher’s Exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. Condensed abstract COX2 (PTGS2) gene

  4. Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma

    PubMed Central

    Miller, Cassandra L.; Muthupalani, Sureshkumar; Shen, Zeli; Drees, Frauke; Ge, Zhongming; Feng, Yan; Chen, Xiaowei; Gong, Guanyu; Nagar, Karan K.; Wang, Timothy C.; Gertler, Frank B.; Fox, James G.

    2016-01-01

    During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections. Predominantly male Lpd-/- mice with RP exhibited lesions consistent with invasive rectal carcinoma concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+ myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting their role in the neoplastic process. An evaluation of Lpd-/- mice with RP compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated that all of these mice exhibit some degree of lower bowel inflammation; however, mice with prolapses had significantly higher degree of focal lesions at the colo-rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice by embryo transfer rederivation, the disease phenotype was abrogated, implicating EHS as a contributing factor in the development of rectal carcinoma. Here we describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma. PMID:27045955

  5. Sexual Function in Males After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Dahl, Alv A.; Skovlund, Eva; Balteskard, Lise; Carlsen, Erik; Fossa, Sophie D.; Tveit, Kjell Magne

    2010-03-15

    Purpose: Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer. Methods and Materials: Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured. Results: Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT- patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate-severe erectile dysfunction in RT+ patients was 7.3 compared with RT- patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01). Conclusion: RT for rectal cancer is associated with significant long-term effects on sexual function in males.

  6. Bladder and rectal complications following radiotherapy for cervix cancer

    SciTech Connect

    Stryker, J.A.; Bartholomew, M.; Velkley, D.E.; Cunningham, D.E.; Mortel, R.; Craycraft, G.; Shafer, J.

    1988-01-01

    One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

  7. Toward Restored Bowel Health in Rectal Cancer Survivors.

    PubMed

    Steineck, Gunnar; Schmidt, Heike; Alevronta, Eleftheria; Sjöberg, Fei; Bull, Cecilia Magdalena; Vordermark, Dirk

    2016-07-01

    As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors.

  8. Recent advances in robotic surgery for rectal cancer.

    PubMed

    Ishihara, Soichiro; Otani, Kensuke; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Junichiro; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Kazama, Shinsuke; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2015-08-01

    Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology.

  9. Patterns of metastasis in colon and rectal cancer

    PubMed Central

    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-01-01

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis. PMID:27416752

  10. Voiding Dysfunction after Total Mesorectal Excision in Rectal Cancer

    PubMed Central

    Kim, Jae Heon; Noh, Tae Il; Oh, Mi Mi; Park, Jae Young; Lee, Jeong Gu; Um, Jun Won; Min, Byung Wook

    2011-01-01

    Purpose The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). Methods This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. Results A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. Conclusions Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition. PMID:22087426

  11. 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

  12. Primary gastrointestinal lymphoma

    PubMed Central

    Aledavood, Amir; Nasiri, Mohammad Reza Ghavam; Memar, Bahram; Shahidsales, Soodabeh; Raziee, Hamid Reza; Ghafarzadegan, Kamran; Mohtashami, Samira

    2012-01-01

    Background: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. Materials and Methods: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Results: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Conclusion: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma. PMID:23626617

  13. Gastrointestinal Physiology and Function.

    PubMed

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Grundy, David

    2017-02-08

    The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

  14. Childhood functional gastrointestinal disorders

    PubMed Central

    Rasquin-Weber, A; Hyman, P; Cucchiara, S; Fleisher, D; Hyams, J; Milla, P; Staiano, A

    1999-01-01

    This is the first attempt at defining criteria for functional gastrointestinal disorders (FGIDs) in infancy, childhood, and adolescence. The decision-making process was as for adults and consisted of arriving at consensus, based on clinical experience. This paper is intended to be a quick reference. The classification system selected differs from the one used in the adult population in that it is organized according to main complaints instead of being organ-targeted. Because the child is still developing, some disorders such as toddler's diarrhea (or functional diarrhea) are linked to certain physiologic stages; others may result from behavioral responses to sphincter function acquisition such as fecal retention; others will only be recognizable after the child is cognitively mature enough to report the symptoms (e.g., dyspepsia). Infant regurgitation, rumination, and cyclic vomiting constitute the vomiting disorders. Abdominal pain disorders are classified as: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain, abdominal migraine, and aerophagia. Disorders of defecation include: infant dyschezia, functional constipation, functional fecal retention, and functional non-retentive fecal soiling. Some disorders, such as IBS and dyspepsia and functional abdominal pain, are exact replications of the adult criteria because there are enough data to confirm that they represent specific and similar disorders in pediatrics. Other disorders not included in the pediatric classification, such as functional biliary disorders, do occur in children; however, existing data are insufficient to warrant including them at the present time. For these disorders, it is suggested that, for the time being, clinicians refer to the criteria established for the adult population.


Keywords: infant vomiting; cyclic vomiting syndrome; functional dyspepsia in children; irritable bowel syndrome in children; functional abdominal pain in children; functional

  15. Electrophysiological characterization of human rectal afferents

    PubMed Central

    Ng, Kheng-Seong; Brookes, Simon J.; Montes-Adrian, Noemi A.; Mahns, David A.

    2016-01-01

    It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and “inflammatory soup” (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3–25) spikes/s vs. 2 (1–4), P < 0.001] and IS [median 5 (range 2–18) spikes/s vs. 2 (1–4), P < 0.001]. Mechanosensitive “hot spots” were identified in 16 nerves [median threshold 2.0 g (range 1.4–6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4–1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. PMID:27789454

  16. Results of radical surgery for rectal cancer.

    PubMed

    Heald, R J; Karanjia, N D

    1992-01-01

    This paper examines the hypothesis that a reduction in the distal mural margin during anterior resection for sphincter conservation in rectal cancer excision is safe, provided total mesorectal excision is undertaken with wash-out of the clamped rectum. One hundred ninety-two patients underwent anterior resection and 21 (less than 10%) patients underwent abdomino-perineal excision (APE) by one surgeon (RJH). Anterior resections were classified as "curative" (79%) and "non-curative" (21%); in the "curative" sub-group less than 4% of patients developed local recurrence. The series was retrospectively analyzed for the effect of mural margins on local recurrence with 152 patients undergoing "curative" anterior resections and 40 patients undergoing "non-curative" resections. In the 152 specimens from curative resections, 110 had a resection margin greater than 1 cm and 42 had a resection margin less than 1 cm. Four patients developed local recurrence in the greater than 1 cm margin group (95% confidence interval: 0.8%-7.8%) and no patients developed local recurrence in the less than or equal to 1 cm margin group (95% confidence interval: 0%-5.9%). In each patient with local recurrence a cause for failure was apparent. There was no statistically significant difference in local recurrence rate between the less than or equal to 1 cm margin group and the greater than 1 cm margin group. A reduction in resection margin therefore did not compromise survival after anterior resection. The significance of lateral resection margins is discussed. The role of deep radiotherapy and cytotoxics are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Neo-adjuvant radiotherapy in rectal cancer

    PubMed Central

    Glimelius, Bengt

    2013-01-01

    In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging. PMID:24379566

  18. Decellularization of human stromal refractive lenticules for corneal tissue engineering

    PubMed Central

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M.; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S.

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  19. A typical presentation of a rare cause of obscure gastrointestinal bleeding

    PubMed Central

    Reuter, Stefan; Bettenworth, Dominik; Mees, Sören Torge; Neumann, Jörg; Beyna, Torsten; Domschke, Wolfram; Wessling, Johannes; Ullerich, Hansjörg

    2011-01-01

    A 52-year-old white woman had suffered from intermittent gastrointestinal (GI) bleeding for one year. Upper GI endoscopy, colonoscopy and peroral double-balloon enteroscopy (DBE) did not detect any bleeding source, suggesting obscure GI bleeding. However, in videocapsule endoscopy a jejunal ulceration without bleeding signs was suspected and this was endoscopically confirmed by another peroral DBE. After transfusion of packed red blood cells, the patient was discharged from our hospital in good general condition. Two weeks later she was readmitted because of another episode of acute bleeding. Multi-detector row computed tomography with 3D reconstruction was performed revealing a jejunal tumor causing lower gastrointestinal bleeding. The patient underwent exploratory laparotomy with partial jejunal resection and end-to-end jejunostomy for reconstruction. Histological examination of the specimen confirmed the diagnosis of a low risk gastrointestinal stromal tumor (GIST). Nine days after surgery the patient was discharged in good health. No signs of gastrointestinal rebleeding occurred in a follow-up of eight months. We herein describe the complex presentation and course of this patient with GIST and also review the current approach to treatment. PMID:21403816

  20. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal

    PubMed Central

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Objective: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. Materials and methods: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. Results: All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. Conclusion: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors. PMID:26884872

  1. Unique considerations in the patient with rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-08-01

    In the past two decades, substantial progress has been made in the adjuvant management of colorectal cancer. Chemotherapy has improved overall survival in patients with node-positive (N+) disease. In contrast with colon cancer, which has a low incidence of local recurrence, patients with rectal cancer have a higher incidence requiring the addition of pelvic radiation therapy (chemoradiation). Patients with rectal cancer have a number of unique management considerations: for example, the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? This review will address these and other controversies specific to patients with rectal cancer.

  2. Metachronous penile metastasis from rectal cancer after total pelvic exenteration.

    PubMed

    Kimura, Yuta; Shida, Dai; Nasu, Keiichi; Matsunaga, Hiroki; Warabi, Masahiro; Inoue, Satoru

    2012-10-14

    Despite its abundant vascularization and extensive circulatory communication with neighboring organs, metastases to the penis are a rare event. A 57-year-old male, who had undergone total pelvic exenteration for rectal cancer sixteen months earlier, demonstrated an abnormal uptake within his penis by positron emission tomography/computed tomography. A single elastic nodule of the middle penis shaft was noted deep within Bucks fascia. No other obvious recurrent site was noted except the penile lesion. Total penectomy was performed as a curative resection based on a diagnosis of isolated penile metastasis from rectal cancer. A histopathological examination revealed an increase of well differentiated adenocarcinoma in the corpus spongiosum consistent with his primary rectal tumor. The immunohistochemistry of the tumor cells demonstrated positive staining for cytokeratin 20 and negative staining for cytokeratin 7, which strongly supported a diagnosis of penile metastasis from the rectum. The patient is alive more than two years without any recurrence.

  3. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  4. Emerging and Evolving Technology in Colon and Rectal Surgery

    PubMed Central

    Bosio, Raul M.; Pigazzi, Alessio

    2015-01-01

    Minimally invasive surgery has changed the way we manage many colon and rectal pathologies. Multiple techniques, from straight laparoscopic procedures, to hand-assisted and single-port techniques are available, requiring surgeons to go through various learning curves. Robotic surgery is a relatively novel technique in general surgery which appears to hold most promise for rectal resection. Laparoscopic rectal procedures are difficult, and even in experienced hands, conversion rates are around 17%. Robotic surgery may be a point of difference in these cases, despite a long learning curve and higher costs. This article will describe the role of robotics in colorectal surgery. Room set up, port placement, and docking strategies will be described for common procedures, with emphasis on a hybrid robotic low anterior resection. PMID:26491407

  5. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

  6. Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy

    SciTech Connect

    Wang Zhou; Jaggernauth, Wainwright; Malhotra, Harish K.; Podgorsak, Matthew B.

    2010-01-01

    In film-based intracavitary brachytherapy for cervical cancer, position of the rectal markers may not accurately represent the anterior rectal wall. This study was aimed at analyzing the variability of rectal dose estimation as a result of interfractional variation of marker placement. A cohort of five patients treated with multiple-fraction tandem and ovoid high-dose-rate (HDR) brachytherapy was studied. The cervical os point and the orientation of the applicators were matched among all fractional plans for each patient. Rectal points obtained from all fractions were then input into each clinical treated plan. New fractional rectal doses were obtained and a new cumulative rectal dose for each patient was calculated. The maximum interfractional variation of distances between rectal dose points and the closest source positions was 1.1 cm. The corresponding maximum variability of fractional rectal dose was 65.5%. The percentage difference in cumulative rectal dose estimation for each patient was 5.4%, 19.6%, 34.6%, 23.4%, and 13.9%, respectively. In conclusion, care should be taken when using rectal markers as reference points for estimating rectal dose in HDR cervical brachytherapy. The best estimate of true rectal dose for each fraction should be determined by the most anterior point among all fractions.

  7. Reproducibility with repeat CT in radiomics study for rectal cancer

    PubMed Central

    Hu, Panpan; Wang, Jiazhou; Zhong, Haoyu; Zhou, Zhen; Shen, Lijun; Hu, Weigang; Zhang, Zhen

    2016-01-01

    Purpose To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Results Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC ≥ 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC ≥ 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). Methods 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. Conclusions Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction. PMID:27669756

  8. Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

    SciTech Connect

    Noyes, William R.; Hosford, Charles C.; Schultz, Steven E.

    2012-04-01

    Objectives: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. Methods: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectal space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Results: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. Conclusions: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.

  9. Staphylococcus aureus Blepharitis Associated with Multiple Corneal Stromal Microabscess, Stromal Edema, and Uveitis.

    PubMed

    Boto-de-los-Bueis, Ana; del Hierro Zarzuelo, Almudena; García Perea, Adela; de Pablos, Manuela; Pastora, Natalia; Noval, Susana

    2015-04-01

    We report a case of an immunocompetent woman with atypical marginal keratitis. She presented with recurrent episodes of multiples microabscess distributed in a triangular pattern associated with stromal oedema and anterior chamber uveitis, affecting both eyes, but not simultaneously. The episodes responded to steroid drops, corneal inflammation was coincidental with a worsening of her blepharitis in the affected eye and S. aureus was isolated from the lids.

  10. Immunological hallmarks of stromal cells in the tumour microenvironment.

    PubMed

    Turley, Shannon J; Cremasco, Viviana; Astarita, Jillian L

    2015-11-01

    A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.

  11. Sex cord-gonadal stromal tumor of the rete testis.

    PubMed

    Sajadi, Kamran P; Dalton, Rory R; Brown, James A

    2009-01-01

    A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.

  12. Bilateral Sclerosing Stromal Ovarian Tumor in an Adolescent

    PubMed Central

    Naidu, Anjani; Chung, Betty; Simon, Mitchell; Marshall, Ian

    2015-01-01

    Sclerosing stromal tumor of the ovary is a rare, benign, sex cord stromal tumor occurring predominantly in younger women in the 2nd and 3rd decades of life. It typically presents unilaterally with only 2 previously reported cases of bilateral presentation. Common clinical presentations include pelvic or abdominal pain, a mass, or menstrual changes. Although occasionally presenting with hormonal manifestations, virilization as a result of androgen production by the tumor is rare. Here we present an extremely rare case of a sclerosing stromal ovarian tumor in a 14-year-old patient with bilateral presentation and with clinical and biochemical evidence of hyperandrogenemia. PMID:26064755

  13. Rectal fist insertion. An unusual form of sexual behavior.

    PubMed

    Shook, L L; Whittle, R; Rose, E F

    1985-12-01

    Rectal fist insertion (fist fucking) is an uncommon and potentially dangerous sexual practice. This is usually a homosexual activity, but can also be a heterosexual or an autoerotic practice. One known death has been reported associated with rectal fist insertion, in which the complications of anal and colonic tears and bleeding had occurred (see Editor's note). The possibility of drug overdose is also probable, as drugs and alcohol are commonly introduced into the rectum to promote sphincter relaxation and to ease the discomfort of anal dilatation.

  14. Total mesorectal excision and management of rectal cancer.

    PubMed

    Pinsk, Ilia; Phang, P Terry

    2007-10-01

    Treatment of rectal cancer over the last two decades has evolved with changes in techniques of surgery and radiation based on national and international trials. Preoperative adjuvant radiation is now preferred over postoperative adjuvant radiation, and total mesorectal excision with preservation of pelvic nerves is the gold standard for surgical treatment of rectal cancer. Preservation of the anal sphincter without compromising oncological outcome is an additional benefit for patients with carcinoma in the distal rectum. Further progress in imaging and a multidisciplinary team approach will facilitate individualization of treatment strategy with more focus on quality of life.

  15. Gene Expression Analysis of Sporadic Early-Onset Rectal Adenocarcinoma

    PubMed Central

    Nfonsam, V; Xu, W; Koblinski, J; Jandova, J

    2016-01-01

    Background Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease. Methods Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. Results When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors. Conclusions Results of

  16. Fatal cerebral air embolism following endoscopic evaluation of rectal stump

    PubMed Central

    Baban, Chwanrow Karim; Murphy, Michael; Hennessy, Tony; O'Hanlon, Deirdre

    2013-01-01

    A 63-year-old man underwent endoscopic evaluation of the rectal stump for rectal bleeding and suffered a massive cerebral air embolism with severe neurological impairment and subsequent death. The patient underwent a Hartmann's procedure 9 month previously for ischaemic bowel and was noted to have portal hypertension at laparotomy. We hypothesise that air entered the venous plexus around rectum and entered the azygos vein via a porto-systemic shunt and travelled retrogradely via the superior vena cava to the venous sinuses of the brain. PMID:23704447

  17. Perineal rectosigmoidectomy for incarcerated rectal prolapse (Altemeier’s procedure)

    PubMed Central

    Sipahi, Mesut; Arslan, Ergin; Börekçi, Hasan; Aytekin, Faruk Önder; Külah, Bahadır; Banlı, Oktay

    2016-01-01

    Perineal procedures have higher recurrence and lower mortality rates than abdominal alternatives for the treatment of rectal prolapse. Presence of incarceration and strangulation also influences treatment choice. Perineal rectosigmoidectomy is one of the treatment options in patients with incarceration and strangulation, with low mortality and acceptable recurrence rates. This operation can be performed especially to avoid general anesthesia in old patients with co-morbidities. We aimed to present perineal rectosigmoidectomy and diverting loop colostomy in a patient with neurological disability due to spinal trauma and incarcerated rectal prolapse. PMID:27528816

  18. Gastrointestinal Amyloidosis Presenting with Multiple Episodes of Gastrointestinal Bleeding

    SciTech Connect

    Kim, Sang Hyeon Kang, Eun Ju; Park, Jee Won; Jo, Jung Hyun; Kim, Soo Jin; Cho, Jin Han; Kang, Myong Jin; Park, Byeong Ho

    2009-05-15

    Amyloidosis is characterized by the extracellular deposition of amyloid protein in various organs. Gastrointestinal involvement in amyloidosis is common, but a diagnosis of amyloidosis is often delayed. Severe gastrointestinal hemorrhage in amyloidosis is rare but can be fatal in some cases. We experienced a case of a 49-year-old man who presented with recurrent massive hematochezia. Although embolization was performed eight times for bleeding from different sites of the small intestine, hematochezia did not cease. We report the case, with a review of the literature.

  19. Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

    PubMed

    Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

    2015-10-16

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.

  20. Gastrointestinal Symptoms of Marathon Runners

    PubMed Central

    Keeffe, Emmet B.; Lowe, Daniel K.; Goss, J. Richard; Wayne, Robert

    1984-01-01

    A survey of 707 participants in the 13th Annual Trail's End Marathon in Seaside, Oregon, showed a high incidence of gastrointestinal disturbances, predominantly of the lower tract, associated with long-distance running. The urge to defecate, both during and immediately after running, occurred in over a third of runners. Bowel movements (35%) and diarrhea (19%) were relatively common after running, and runners occasionally interrupted hard runs or races for bowel movements (18%) or diarrhea (10%). Lower gastrointestinal disturbances were more frequent in women than in men and in younger than in older runners. Awareness of the frequency and nature of gastrointestinal symptoms documented by this survey will assist physicians in evaluating abdominal complaints in runners. PMID:6506684