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Sample records for primary cervical carcinoma

  1. Induction chemotherapy followed by radiotherapy in patients with cervical lymph node metastases from unknown primary carcinoma.

    PubMed

    Seol, Young Mi; Choi, Young Jin; Lee, Byung Joo; Wang, Soo Geun

    2015-03-01

    Cervical metastases from unknown primary tumors are rare and no clear therapeutic options are available. This study was performed to assess the efficacy and safety profiles of induction chemotherapy followed radiotherapy in patients with cervical lymph node metastases from unknown primary cancer. Patients with histological diagnosis of cervical lymph-node metastasis from carcinoma with an unknown primary cancer underwent induction chemotherapy followed by radiotherapy. All patients had squamous cell carcinoma. Induction chemotherapy consisted of 3-4 cycles every 3 weeks of docetaxel (day 1.70 mg/m(2)) and cisplatin (day 1.75 mg/m(2)). Radiation therapy (RT) was started with in 10 weeks of the last cycle of chemotherapy, and it was administered 5 days per week. It was given in daily fractions of (1.8) Grays (Gy) of 2 Gy and the total dose to the primary tumor was 70-74 Gy. Neck dissection was reserved for residual disease after definitive radiotherapy. Overall survival, recurrent free survival, and locoregional control were calculated using the Kaplan-Meier method. Twenty one patients with an unknown primary cancer underwent induction chemotherapy and radiotherapy. After induction chemotherapy, 6 patients achieved CR and 8 patients achieved PR. The overall response rate after radiation, was 90.4 % (19 of 21 patients). Neutropenia and infection were the most common grade 3-4 adverse event during induction chemotherapy. Mucositis and dermatitis were the most common grade 3-4 toxicities during radiotherapy. With a median follow-up of 50.6 months, the estimated 2 years OS rates were 71 ± 6 %, respectively. The median OS was 42 months (95 % confidence interval CI 8-65 months). The recurrent-free survival rate at 2 years was 57 %, respectively. In the patients with responder to induction chemotherapy, superior relapse free survival and overall survival rate observed. No occurrence of primary cancer was observed during the follow-up period. Induction

  2. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  3. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary.

    PubMed

    Jereczek-Fossa, Barbara A; Jassem, Jacek; Orecchia, Roberto

    2004-04-01

    Cervical lymph node metastases of squamous cell carcinoma from occult primary constitute about 2-5% of all patients with carcinoma of unknown primary site (CUP). Metastases in the upper and middle neck are generally attributed to head and neck cancers, whereas the lower neck (supraclavicular area) involvement is often associated with primary malignancies below the clavicles. The diagnostic procedures include physical examination with thorough evaluation of the head and neck mucosa using fiber-optic endoscopy, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computer tomography and/or magnetic resonance. A systematic tonsillectomy in the absence of suspicious lesions is often recommended since up to 25% of primary tumors can be detected in this site. The thoracic primary (tracheal, bronchial, lung, esophagus) has to be excluded, especially in the case of lower neck involvement. Positron emission tomography (PET) with fluoro-2-deoxy-D-glucose allows detection of primary tumor in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (lymph node excision or neck dissection), with or without postoperative radiotherapy, radiotherapy alone and radiotherapy followed by surgery. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) necessitate combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighted against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined. PMID:15023433

  4. Hepatocellular Carcinoma with Cervical Spine and Pelvic Bone Metastases Presenting as Unknown Primary Neoplasm.

    PubMed

    Hwang, Sea Won; Lee, Ji Eun; Lee, Jung Min; Hong, Sook Hee; Lee, Myung Ah; Chun, Hoo Geun; Chun, Ho Jong; Lee, Sung Hak; Jung, Eun Sun

    2015-07-01

    The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.

  5. Palliative Care in Improving Quality of Life in Patients With High Risk Primary or Recurrent Gynecologic Malignancies

    ClinicalTrials.gov

    2015-10-15

    Cervical Carcinoma; Ovarian Carcinoma; Primary Peritoneal Carcinoma; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vulvar Carcinoma; Uterine Corpus Cancer; Vulvar Carcinoma; Peritoneal Neoplasms

  6. P16 and HPV discordance in metastatic carcinoma of cervical lymph nodes of unknown primary

    PubMed Central

    Ralph, Alyssa; Meyer, Andrew; Sirota, Ronald; Hooberman, Arthur

    2015-01-01

    Key Clinical Message The prognostic utility of HPV in oropharyngeal squamous cell carcinoma (OPSCC) and non-OPSCC as has been well documented. Currently, a standardized IHC scoring system does not exist and is needed to define HPV positivity. We have recently seen a patient that provides a caution in using p16 status as a diagnostic aid. PMID:26509014

  7. Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas

    SciTech Connect

    Duerst, M.; Croce, C.M.; Gissmann, L.; Schwarz, E.; Huebner, K.

    1987-02-01

    The chromosomal locations of cellular sequences flanking integrated papillomavirus DNA in four cervical cell lines and a primary cervical carcinoma have been determined. The two human papillomavirus (HPV) 16 flanking sequences derived from the tumor were localized to chromosomes regions 20pter..-->..20q13 and 3p25..-->..3qter, regions that also contain the protooncogenes c-src-1 and c-raf-1, respectively. The HPV 16 integration site in the SiHa cervical carcinoma-derived cell line is in chromosome region 13q14..-->..13q32. The HPV 18 integration site in SW756 cervical carcinoma cells is in chromosome 12 but is not closely linked to the Ki-ras2 gene. Finally, in two cervical carcinoma cell lines, HeLa and C4-I, HPV 18 DNA is integrated in chromosome 8, 5' of the c-myc gene. The HeLaHPV 18 integration site is within 40 kilobases 5' of the c-myc gene, inside the HL60 amplification unit surrounding and including the c-myc gene. Additionally, steady-state levels of c-myc mRNA are elevated in HeLa and C4-I cells relative to other cervical carcinoma cell lines. Thus, in at least some genital tumors, cis-activation of cellular oncogenes by HPV may be involved in malignant transformation of cervical cells.

  8. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

    PubMed Central

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  9. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

    PubMed

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  10. [Primary cervical cancer screening].

    PubMed

    Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

    2015-01-01

    Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis.

  11. Carcinoma of the cervical esophagus: diagnosis, management, and results

    SciTech Connect

    Lee, D.J.; Harris, A.; Gillette, A.; Munoz, L.; Kashima, H.

    1984-11-01

    Nine of 168 patients (5.3%) with carcinoma of the esophagus had primary tumors in the cervical esophagus. The principal symptoms and signs of carcinoma of the cervical esophagus were dysphagia, hoarseness, neck mass, and weight loss. The esophagogram was a very reliable study, revealing the abnormality in all nine patients. The true extent of the disease was better delineated by computerized tomography which demonstrated not only the intraluminal mass but also the extraesophageal spread. Endoscopic examination of the cervical esophagus was the definitive procedure to establish the diagnosis. All nine patients were treated with definitive radiotherapy, three surviving two to five years. The major cause of death was the failure to control local disease. 14 references, 3 tables.

  12. The molecular genetics of cervical carcinoma

    PubMed Central

    Lazo, P A

    1999-01-01

    In the pathogenesis of cervical carcinoma there are three major components, two of them related to the role of human papillomaviruses (HPV). First, the effect of viral E6 and E7 proteins. Second, the integration of viral DNA in chromosomal regions associated with well known tumour phenotypes. Some of these viral integrations occur recurrently at specific chromosomal locations, such as 8q24 and 12q15, both harbouring HPV18 and HPV16. And third, there are other recurrent genetic alterations not linked to HPV. Recurrent losses of heterozygosity (LOH) have been detected in chromosome regions 3p14–22, 4p16, 5p15, 6p21–22, 11q23, 17p13.3 without effect on p53, 18q12–22 and 19q13, all of them suggesting the alteration of putative tumour suppressor genes not yet identified. Recurrent amplification has been mapped to 3q+ arm, with the common region in 3q24–28 in 90% of invasive carcinomas. The mutator phenotype, microsatellite instability, plays a minor role and is detected in only 7% of cervical carcinomas. The development of cervical carcinoma requires the sequential occurrence and selection of several genetic alterations. The identification of the specific genes involved, and their correlation with specific tumour properties and stages could improve the understanding and perhaps the management of cervical carcinoma. © 1999 Cancer Research Campaign PMID:10471054

  13. Primary pulmonary cavitating carcinomas

    PubMed Central

    Chaudhuri, M. Ray

    1973-01-01

    A primary lung cancer can produce a cavity in three ways. The first is `cavitary necrosis' due to breakdown of the growth itself. The second is `stenotic abscess' due to infection and breakdown of the lung parenchyma distal to bronchial obstruction caused by the growth. The third type is `spill-over abscess'. In the present series, necrosis and cavitation were observed in 100 cases out of a total of 632 primary bronchial carcinomas seen at the London Chest Hospital from July 1967 to June 1970. There were 91 males and nine females with an average age of 58·45 years. All except one smoked very heavily and had considerable symptoms. The size of the cavities ranged from 1 to 10 cm and their wall thickness from 0·5 to 3 cm. They were single in 92 cases and multiple (up to four) in eight. In 42 cases, the cancerous cavitation was central, in 38 intermediate, and in 20 peripheral. The segments most frequently affected were the apicoposterior segment of the left upper lobe and the superior segment of the left lower lobe. For descriptive purposes, these cavitating carcinomas were also divided into six broad groups on the basis of radiological and pathological correlations. Neoplastic cells in the sputum were found in 64 cases. Bronchoscopy revealed growth in 42 cases and biopsy was positive in 48. The main microscopic feature was vascular invasion of medium-sized muscular arteries and veins found in the vicinity of every cavitating bronchial carcinoma. Invasion along with tumour plugging of the vessels was observed in 75 cases and thrombosis alone in 55 cases. There were 82 squamous-cell carcinomas, 11 undifferentiated carcinomas of large polygonal-cell type, and seven adeno-alveolar cell carcinomas. The single most important and noteworthy feature in the present series was that oat-cell carcinoma hardly ever undergoes necrosis. Out of a total of 95 cases observed, only three showed necrosis, and this was minimal and characteristically devoid of cavitation. In oat

  14. Independent bilateral primary bronchial carcinomas

    PubMed Central

    Chaudhuri, M. Ray

    1971-01-01

    Independent bilateral primary bronchial carcinomas are not common. Since Beyreuther's description in 1924, 16 well-documented cases of independent primary bronchial carcinomas of different histology have been described. From 1965 to 1970, eight cases were seen at the London Chest Hospital. In order to make the diagnosis of a second primary bronchial carcinoma, each tumour should be malignant and neither should be a metastasis from the other. To meet this last criterion, the histopathological features of the two tumours must be different. Many cases have been described in the literature as double primary bronchial carcinomas where the second primary had the same histological features as the first. Images PMID:4327711

  15. Uterine cervical carcinoma after therapy: CT and MR imaging findings.

    PubMed

    Jeong, Yong Yeon; Kang, Heoung Keun; Chung, Tae Woong; Seo, Jeong Jin; Park, Jin Gyoon

    2003-01-01

    Cervical carcinoma is one of the most frequent causes of death in women. Computed tomography (CT) and magnetic resonance (MR) imaging are the primary modalities for follow-up of treated cervical carcinoma. A normal vaginal cuff after hysterectomy appears as a smooth, low-signal-intensity muscular wall on T2-weighted MR images. Early (2-3 months after treatment) and significant decreases in the signal intensity and volume of the tumor at MR imaging indicate a good response to radiation therapy. Sites of recurrence are the pelvis, lymph nodes, and distant sites. Pelvic recurrence appears as a heterogeneously enhancing mass at contrast material-enhanced CT and often appears as a heterogeneous, high-signal-intensity mass at T2-weighted MR imaging. Lymph node recurrence ranges from scattered, minimally enlarged nodes to large, conglomerate nodal masses. Determination of neoplastic infiltration of lymph nodes is based on size; most researchers consider nodes greater than 1 cm in short-axis diameter to be metastatic. Distant metastases are usually due to recurrent disease and occur in the abdomen, thorax, and bone. Knowledge of the normal therapeutic changes and the spectrum of recurrent tumor in patients with cervical carcinoma is important for accurate interpretation of follow-up CT and MR images.

  16. Primary duodenal carcinoma.

    PubMed Central

    Adedeji, O. A.; Trescoli-Serrano, C.; Garcia-Zarco, M.

    1995-01-01

    Eight cases of primary duodenal carcinoma in a district general hospital are presented. The cases highlight the advanced state of the disease at presentation, the difficulty in diagnosis, and its poor prognosis. Duodenal carcinoma occurs in both sexes worldwide with no predisposing factors in the majority of cases. There is an increased risk in patients with familial adenomatous polyposis and adenomas of the duodenum. Duodenal carcinoma occurs about 22 years from the diagnosis of familial adenomatous polyposis in about 2% of patients, forming over 50% of upper gastrointestinal cancers occurring in these patients. Carcinomatous changes occur in 30 to 60% of duodenal villous adenomas and much less in tubulo-villous and tubular adenomas. These categories of patients should be screened and adequately followed up. Aggressive and radical surgery, even in the presence of locally advanced disease and lymph node involvement, gives a better outcome. When curative surgery is not possible, chemotherapy must accompany palliation with or without radiotherapy. Pre-operative chemotherapy may facilitate a curative radical resection. The general five-year survival is 17-33% but some centres have achieved a five-year survival of 40-60% with aggressive management of these patients. PMID:7644397

  17. Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

    SciTech Connect

    Frank, Steven J.; Rosenthal, David I.; Petsuksiri, Janjira; Ang, K. Kian; Morrison, William H.; Weber, Randal S.; Glisson, Bonnie S.; El-Naggar, Adel K.; Garden, Adam S.

    2010-11-15

    Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and the survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.

  18. Primary biliary carcinoma: CT evaluation

    SciTech Connect

    Thorsen, M.K.; Quiroz, F.; Lawson, T.L.; Smith, D.F.; Foley, W.D.; Steward, E.T.

    1984-08-01

    Fifty-three patients with documented primary biliary carcinoma were studied with computed tomography. Twenty-six patients had gallbladder carcinoma and 27 patients had carcinoma of the biliary ductal system. Ninety percent of patients with gallbladder cancer had an intraluminal mass. Local invasion into the liver was common. The majority of patients with biliary ductal carcinoma had dilated bile ducts, while only 50% of patients with gallbladder cancer had biliary ductal dilatation. The most common location of tumor involving the extrahepatic biliary ductal system was the distal common bile duct. This occurred in eight patients out of 27, or 30% of the cases.

  19. Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

    ClinicalTrials.gov

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  20. Cervical Cord Compression as Initial Presentation of Papillary Thyroid Carcinoma: a Case Report.

    PubMed

    Selvakumar, Veda Padma Priya; Goel, Ashish; Kumar, Kapil

    2016-09-01

    Cervical cord compression secondary to extension of a long standing papillary thyroid carcinoma as well as multiple cases of distal cord compression from occult follicular thyroid carcinoma have been reported. But cervical cord compression from Papillary Thyroid Carcinoma has not been reported so far. Forty eight year old lady presented with progressive quadriparesis of 2 months duration. MRI of the cervical spine showed destructive lesion with soft tissue component in vertebral bodies and posterior elements of C4-C6 vertebrae with cord compression along with a large thyroid mass extending to retrosternal region likely malignant. USG guided FNAC & Biopsy of thyroid lesion was inconclusive. She underwent Preoperative Selective angioembolisation for vertebral metastasis followed by total thyroidectomy with cervical cord decompression, bone grafting and plating. HPE reported follicular variant of Papillary Thyroid carcinoma. Four weeks postoperatively she underwent radioiodine ablation by 263 mci of I 131. She then received palliative EBRT to cervical and dorsal spine 30 Gy/10 fractions. She is alive and neurologically stable at 6 months follow up. Papillary thyroid carcinoma has an excellent prognosis. Hence a prompt management of primary disease and aggressive approach to metastatic lesion may prolong survival and allow favorable prognosis. PMID:27651699

  1. DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis.

    PubMed

    Wang, Han; Gao, Weiwei

    2016-01-01

    BACKGROUND This study aimed to investigate the expression of DJ-1 in cervical carcinoma and its effects on cell viability and apoptosis. MATERIAL AND METHODS Cervical carcinoma cell line Hela and 85 tissue samples, including 45 primary tumor biopsies, 30 para-carcinoma tissues, and 10 normal cervical tissues samples were used in this study. The expressions of DJ-1 in cervical carcinoma tissue, para-carcinoma tissue, and normal tissue samples were investigated by immunohistochemistry. DJ-1 expression in Hela cells was also investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. DJ-1 was interfered and transfected with siRNA, then cell viability and apoptosis were assayed by MTT and flow cytometry, respectively. Additionally, the expressions of phosphatase and tensin homolog (PTEN), AKT, and phospho-AKT (P-AKT) were detected. RESULTS Immunohistochemistry results showed that DJ-1 was highly expressed in cervical carcinoma tissues. In Hela cells, the expression of DJ-1 was significantly higher than that in normal controls (P<0.05). When cells were treated with DJ-1 siRNA, the cell viability decreased significantly (P<0.05), and the percentage of apoptosis cells increased significantly (P<0.05). In addition, the expressions of PTEN and AKT were significantly higher in the DJ-1 siRNA treatment group than those in the control group (P<0.05). The expression of p-AKT was significantly lower in the DJ-1 siRNA treatment group than in the control group and the DJ-1 over-expression group (P<0.05). CONCLUSIONS The aberrant up-regulation of DJ-1 expression might be an important step in the pathogenesis of cervical carcinoma. PMID:27544688

  2. DJ-1 Expression in Cervical Carcinoma and its Effects on Cell Viability and Apoptosis

    PubMed Central

    Wang, Han; Gao, Weiwei

    2016-01-01

    Background This study aimed to investigate the expression of DJ-1 in cervical carcinoma and its effects on cell viability and apoptosis. Material/Methods Cervical carcinoma cell line Hela and 85 tissue samples, including 45 primary tumor biopsies, 30 para-carcinoma tissues, and 10 normal cervical tissues samples were used in this study. The expressions of DJ-1 in cervical carcinoma tissue, para-carcinoma tissue, and normal tissue samples were investigated by immunohistochemistry. DJ-1 expression in Hela cells was also investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. DJ-1 was interfered and transfected with siRNA, then cell viability and apoptosis were assayed by MTT and flow cytometry, respectively. Additionally, the expressions of phosphatase and tensin homolog (PTEN), AKT, and phospho-AKT (P-AKT) were detected. Results Immunohistochemistry results showed that DJ-1 was highly expressed in cervical carcinoma tissues. In Hela cells, the expression of DJ-1 was significantly higher than that in normal controls (P<0.05). When cells were treated with DJ-1 siRNA, the cell viability decreased significantly (P<0.05), and the percentage of apoptosis cells increased significantly (P<0.05). In addition, the expressions of PTEN and AKT were significantly higher in the DJ-1 siRNA treatment group than those in the control group (P<0.05). The expression of p-AKT was significantly lower in the DJ-1 siRNA treatment group than in the control group and the DJ-1 over-expression group (P<0.05). Conclusions The aberrant up-regulation of DJ-1 expression might be an important step in the pathogenesis of cervical carcinoma. PMID:27544688

  3. Thyroid adenoma and nasopharyngeal carcinoma with metastasis to cervical lymph nodes is misdiagnosed and treated for thyroid carcinoma: A case report

    PubMed Central

    ZHANG, MIAO; WANG, HENG; PAN, XUEFENG; WU, WENBIN; ZHANG, HUI

    2016-01-01

    Lymph node metastasis of nasopharyngeal carcinoma follows an orderly pattern, and diagnosis of nasopharyngeal carcinoma is often made by lymph node biopsy. In the present study, following neck palpation, ultrasonography and cervical computer tomography, a 52-year-old female patient with thyroid adenoma and enlarged cervical lymph nodes was misdiagnosed as thyroid carcinoma without undergoing preoperative biopsy, followed by unnecessary total thyroidectomy. Systematic CT scan and nasal endoscopic biopsy confirmed the correct diagnosis of primary NPC concurrent with thyroid adenoma. The patient received palliative radiotherapy and L-thyroxine substitution therapy, and was followed up closely via internet-based approaches with life-style intervention, medication consultation and psychological support for improvement of life quality after radiotherapy. In conclusion, primary malignancies with thyroid metastasis must be considered in the differential diagnosis of thyroid tumors with enlarged cervical lymph nodes. PMID:27347179

  4. Carcinoma of the cervical esophagus treated with radiation therapy

    SciTech Connect

    Mendenhall, W.M.; Parsons, J.T.; Vogel, S.B.; Cassisi, N.J.; Million, R.R.

    1988-07-01

    This is an analysis of 34 patients with carcinoma of the cervical esophagus treated with radiation therapy with curative intent at the University of Florida between September 1966 and May 1985. All patients have a minimum 2-year follow-up and 28 (82%) have at least 5 years of follow-up. Patients were staged according to the recommendations of the AJCC. Patients who died within 2 years of treatment with the primary site continuously disease-free were excluded from the local control analysis; all patients were included in the analysis of complications and survival. Irradiation resulted in control of the primary lesion in 1 of 2 patients who presented with T1 lesions, in 4 of the 12 patients with T2 lesions, and 3 of 17 patients who presented with T3 lesions. One patient with a T3 lesion that recurred locally was successfully salvaged by an operation. The 5-year absolute survival rates by stage were as follows: no patients with stage I lesions survived; of 11 stage II patients, one survived; and of 16 stage III patients, three survived. Interestingly, all four of the 5-year survivors were women.

  5. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-06-24

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  6. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  7. Matrix metalloproteinase-14 expression and its prognostic value in cervical carcinoma.

    PubMed

    Wang, Huayi; Zhang, Xianhua; Huang, Liming; Li, Jia; Qu, Shuyun; Pan, Fenglian

    2014-11-01

    The objective of the study was to evaluate the expression of matrix metalloproteinase-14 (MMP-14) in cervical carcinoma and correlate its expression with clinicopathological parameters, recurrence, and survival of the patients. The expressions of MMP-14 in normal cervical mucosa and cervical carcinoma tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. The positive expression rate of MMP-14 in cervical carcinoma tissue was 81.6 %(111/136), and there was significant difference on their positive expression rates between in cervical carcinoma tissue and in normal cervical mucosa(22.4 %)(13/58)(P < 0.05);The positive expression rates of MMP-14 in patients with poor histologic differentiation, lymph node metastasis, and recurrence group were heightened. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expressions of MMP-14 revealed a highly significant difference in human cervical carcinoma tissue (P < 0.05), which suggests that overexpression of MMP-14 is associated with a worse prognosis. The MMP-14 which promotes angiogenes is associated with lymph node metastasis, vascular invasion, and poor prognosis of cervical carcinoma. The current study shows that MMP-14 may be an independent prognostic factor for cervical carcinoma patients.

  8. EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

    ClinicalTrials.gov

    2013-01-15

    Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  9. Cervical Carcinoma in a Renal Transplant Recipient: A Case Report.

    PubMed

    Tuncer, Hasan Aykut; Kirnap, Mahir; Dursun, Polat; Ayhan, Ali; Moray, Gokhan; Haberal, Mehmet

    2016-02-01

    A range of cancer types, at increased rates, is described in renal transplant recipients receiving immunosuppression. Aside from immunodeficiency, heightened medical surveillance for cancer, lifestyle, and other risk factors all play a role. Although the relation between cancer risk and degree of immunodeficiency might not be linear, and might be different for a wide range of cancer subtypes, human papillomavirus-related cancers in long-term transplant recipients may suggest the role of even modest immunosuppression, when present long enough. High-risk human papillomavirus types are recognized as the cause of cancer of the cervix. We report a 49-year-old female renal transplant recipient diagnosed with cervical squamous cell carcinoma, 5 years after the transplant. Based on this patient, we highlight difficulties in surgical approach and the importance of close clinical follow-up including regular gynecologic screening for cervical premalignant and malignant lesions.

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

    ClinicalTrials.gov

    2016-10-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

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

    ClinicalTrials.gov

    2016-11-01

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  12. Management of lymphocysts after cervical carcinoma surgery.

    PubMed

    Charkviani, L; Kekelidze, N; Charkviani, T

    2000-01-01

    In the Gynecological Clinic of the Oncological National Center of Georgia from 1964 to 1999 1,805 extended hysterectomies due to carcinoma of the cervix uteri were performed. Retroperitoneal lymphocysts were revealed in 4.3% of the cases. Of all stage I disease lymphocysts had developed in 2.8% of cases and in stage II 7.2%. Correlations between lymph node metastatic damage and development of lymphocysts were not found. The peak incidence (6.2-6.4%) of lymphocysts appeared to be in women younger than 30 and in elderly women (over 60 years). Unilateral lymphocysts developed more frequently (left-side in 38.9% in right-side in 33.3%) than bilateral ones (28.3%). In 32.5% of cases the size was less than 5 cm, in 42.3% of cases 6-10 cm and in 25.6% of cases more than 10 cm; 18% of the lymphocysts were asymtomatic and did not need any treatment. High temperature, pain, changes in blood occurring 4-5 days after surgery are indications of parametritis. Lymphocysts usually arise 11-12 days after surgery. Ultrasonography is a highly informative diagnosic method to detect this disease. In 23% of cases, the method of treatment was conservative therapy, 35.8% of patients had punctures, thus micro-drainage was performed and a cocktail injection into the cyst cavity was carried out. In 7.7% of cases lymphocyst resection and drainage was carried out.

  13. Merkel Cell Carcinoma of Unknown Primary Origin

    PubMed Central

    Deneve, Jeremiah L.; Messina, Jane L.; Marzban, Suroosh S.; Gonzalez, Ricardo J.; Walls, Brooke M.; Fisher, Kate J.; Ann Chen, Y.; Wayne Cruse, C.; Sondak, Vernon K.; Zager, Jonathan S.

    2015-01-01

    Background Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. Methods After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. Results From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. Conclusions Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients. PMID:22271206

  14. Primary prevention of hepatocellular carcinoma.

    PubMed

    Yu, S Z

    1995-01-01

    Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly, the mortality rates in 1990 (per 100,000) were 20.10 in certain cities and 24.32 in certain counties. More than 90% of HCC cases and 70% of controls were infected with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10-50). In the same group of patients, 8-27% of those with HCC and 0-11% of the healthy controls were also infected with hepatitis C (HCV) (OR = 2.11-17.29). There appears to be some correlation between HBV markers and the OR. The government requires that 85% of infants be immunized with HBV vaccine. In 1992, there were 3 million infants inoculated with HB vaccines. Aflatoxins have been found as contaminants in food, particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake of aflatoxin B1 (AFB1) by people of ten different villages correlated with HCC mortality rates (r = 0.55; P < 0.05). The concentration of AFB1-albumin adducts is an indicator of individual exposure to aflatoxins. These adducts are higher in hyperendemic HCC areas and cases. Most people have now changed their staple food and eat rice instead of corn. Six large epidemiological studies have confirmed that people who drink pond-ditch water experience higher HCC mortality rates than people who drink deep-well water. Recent research has found that the blue-green algal toxin microcystin (MCYST) was a contaminant of pond-ditch water. MCYST is a strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver necrosis. More than 80% of people in Qidong County have already changed their sources of water from pond-ditches to deep wells. Therefore, a combined strategy of the prevention of hepatitis, control of crops and control of drinking water is advocated for the primary prevention of HCC in China.

  15. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  16. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    PubMed

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers. PMID:26700669

  17. [A Case of Cystic Cervical Lymph Node Metastasis of HPV-positive Tonsil Cancer, Being Discriminated as the Branchiogenic Carcinoma].

    PubMed

    Kambara, Rumi; Tamai, Masamitsu; Horii, Arata

    2016-02-01

    In recent years, human papillomavirus (HPV)-positive oropharyngeal carcinomas have been increasing. The first manifestation of these tumors is frequently as cystic metastasis to cervical lymph nodes that may precede recognition of the primary tumor, so, they often result in misdiagnosis as branchial cleft cysts. We report a case of cystic cervical lymph node metastasis of HPV-positive tonsil cancer. The patient was a 70-years-old man who noticed a mass on his left neck. The tumor was large and soft, and it was diagnosed as benign in fine-needle aspiration cytology. We diagnosed the tumor as a branchial cleft cyst and undertook surgery. The histopathological diagnosis was squamous cell carcinoma arising from a branchiogenic cyst. However, because it did not satisfy the diagnostic criteria, we diagnosed the tumor as an unknown primary tumor. One year later, left tonsil cancer was suspected based on PET-CT imaging and a left tonsillectomy was undertaken, whereafter tonsil cancer was found. In p16 immunostaining, it was positive in both cystic mass and tonsil. The cervical mass was cystic lymph node metastasis of HPV-positive tonsil cancer. It is important to investigate the oropharynx, when we found cystic cervical mass, because HPV-positive oropharyngeal carcinoma frequently results in cystic neck metastasis.

  18. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-06-17

    Effects of Immunotherapy; Metastatic/Recurrent Cervical Cancer; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  19. Primary Intraosseous Mucoepidermoid Carcinoma of the Maxilla.

    PubMed

    Nallamilli, S M; Tatapudi, R; Reddy, R S; Ravikanth, M; Rajesh, N

    2015-06-01

    Primary intraosseous mucoepidermoid carcinoma (PIOC) is an infrequent malignancy of the head and neck that exhibits diverse biological behavior. The rareness of the location for a salivary gland tumor and the clinical and radiographic manifestations, suggestive of an odontogenic lesion often pose a diagnostic challenge. We hereby report such a unique case of central mucoepidermoid carcinoma that presented in an ambiguous manner, developing in the maxilla and intruding into the adjacent vital structures, adding a literature review. PMID:26339097

  20. Transcriptional changes induced by epigenetic therapy with hydralazine and magnesium valproate in cervical carcinoma.

    PubMed

    De la Cruz-Hernández, Erick; Perez-Plasencia, Carlos; Pérez-Cardenas, Enrique; Gonzalez-Fierro, Aurora; Trejo-Becerril, Catalina; Chávez-Blanco, Alma; Taja-Chayeb, Lucia; Vidal, Silvia; Gutiérrez, Olga; Dominguez, Guadalupe I; Trujillo, Jaenai E; Duenas-González, Alfonso

    2011-02-01

    Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases is a promising cancer therapy. Experimental data demonstrate that these inhibitors in combination do not only show synergy in antitumor effects but also in whole genome global expression. Ten pairs of pre- and post-treatment cervical tumor samples were analyzed by microarray analysis. Treatment for seven days with hydralazine and valproate (HV) in patients up-regulated 964 genes. The two pathways possessing the highest number of up-regulated genes comprised the ribosome protein and the oxidative phosphorylation pathways, followed by MAPK signaling, tight junction, adherens junction, actin cytoskeleton, cell cycle, focal adhesion, apoptosis, proteasome, Wnt signaling, and antigen processing and presentation pathways. Up-regulated genes by HV, clustered with down-regulated genes in untreated primary cervical carcinomas and were more alike as compared with up-regulated genes from untreated patients in terms of gene ontology. Increased acetylated p53 was also observed. Epigenetic therapy with HV leads to gene reactivation in primary tumors of cervical cancer patients as well as protein acetylation. A number of these reactivated genes have a definitive role as a tumor suppressors. The global expression pattern induced by HV suggests this therapy has an impact on pathways related to energy production which may promote apoptosis.

  1. Dosimetric analysis at ICRU reference points in HDR-brachytherapy of cervical carcinoma.

    PubMed

    Eich, H T; Haverkamp, U; Micke, O; Prott, F J; Müller, R P

    2000-01-01

    In vivo dosimetry in bladder and rectum as well as determining doses on suggested reference points following the ICRU report 38 contribute to quality assurance in HDR-brachytherapy of cervical carcinoma, especially to minimize side effects. In order to gain information regarding the radiation exposure at ICRU reference points in rectum, bladder, ureter and regional lymph nodes those were calculated (digitalisation) by means of orthogonal radiographs of 11 applications in patients with cervical carcinoma, who received primary radiotherapy. In addition, the doses at the ICRU rectum reference point was compared to the results of in vivo measurements in the rectum. The in vivo measurements were by factor 1.5 below the doses determined for the ICRU rectum reference point (4.05 +/- 0.68 Gy versus 6.11 +/- 1.63 Gy). Reasons for this were: calibration errors, non-orthogonal radiographs, movement of applicator and probe in the time span between X-ray and application, missing connection of probe and anterior rectal wall. The standard deviation of calculations at ICRU reference points was on average +/- 30%. Possible reasons for the relatively large standard deviation were difficulties in defining the points, identifying them on radiographs and the different locations of the applicators. Although 3 D CT, US or MR based treatment planning using dose volume histogram analysis is more and more established, this simple procedure of marking and digitising the ICRU reference points lengthened treatment planning only by 5 to 10 minutes. The advantages of in vivo dosimetry are easy practicability and the possibility to determine rectum doses during radiation. The advantages of computer-aided planning at ICRU reference points are that calculations are available before radiation and that they can still be taken into account for treatment planning. Both methods should be applied in HDR-brachytherapy of cervical carcinoma. PMID:10994367

  2. Cervical lymph node metastases from remote primary tumor sites

    PubMed Central

    López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

  3. Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology

    PubMed Central

    Xu, Ruiping; Ke, Yang

    2016-01-01

    Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma. PMID:26735580

  4. Motor sequence learning and motor adaptation in primary cervical dystonia.

    PubMed

    Katschnig-Winter, Petra; Schwingenschuh, Petra; Davare, Marco; Sadnicka, Anna; Schmidt, Reinhold; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2014-06-01

    Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect "contamination" rather than being directly pathological.

  5. Radiation Therapy Plus Cisplatin and Gemcitabine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-12-23

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  6. Primary carcinoma of renal calyx.

    PubMed

    Williams, Phillip A; Mai, Kien T

    2013-10-01

    Renal calyx carcinoma (RCXC) may mimic collecting duct carcinoma (CDC) or urothelial carcinoma (UC) of the renal pelvis. RCXC is distinguished from CDC and UC of the renal pelvis as having the tumor epicenter in the renal calyx, with limited involvement of the surrounding renal pelvis surface urothelium. In this study, we summarize our experience with this entity. Ten cases of RCXC, including 9 cases with urothelial differentiation (RCXC-UC) and 1 case with salivary gland-type differentiation (RCXC-SC), were identified. Ten consecutive cases of UC were selected for comparison, with extensive renal pelvis involvement and with secondary renal parenchymal invasion. Two cases of collecting duct carcinoma (CDC) were also examined. Immunohistochemistry (IHC) was performed on representative tissue blocks for PAX8, PAX2, CK5, CK7, CK20, p63, GATA3, AMACR, RCC, CD10, vimentin, S100, and MSA. The 10 cases of RCXC (M:F=4:6, ages: 62-91 years, mean: 76) presented with renal masses of 3-6cm. Ureteroscopic studies and renal pelvic washings showed atypical/malignant cells in three cases. Seven patients were treated with nephrectomy followed by radiation±chemotherapy, and all cases developed metastases to lymph nodes or liver/lung/bone. In all 7 cases with nephrectomy, there was extensive renal parenchymal involvement with infiltrating borders and diffuse spread along collecting ducts. Six RCXC-UC contained focal squamous differentiation. The RCXC-SC displayed features of adenoid cystic and basaloid features. In situ UC, with or without papillary components, was identified in the calyces in all 7 nephrectomy cases with remaining renal pelvis harboring small tumor burden in 5 cases, and no tumor in another 2 cases. Of the three cases without nephrectomy, no tumor in the renal pelvis could be visualized with endoscopy, however one case was associated with UC of the urinary bladder. Of 10 control UC cases, tumor was limited to the tip of renal papilla in 7 cases, extensive in 3

  7. EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma.

    PubMed

    Zhang, Wei; Jiang, Yinghao; Yu, Qingmiao; Qiang, Shaoying; Liang, Ping; Gao, Yane; Zhao, Xingye; Liu, Wenchao; Zhang, Ju

    2015-10-01

    Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor-sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor-sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P<0.01). This study suggested that there was no EGFR tyrosine kinase inhibitor-sensitive mutation in EGFR exons 18, 19, and 21 in Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation was common and it might be associated with HPV 16 infection in Chinese cervical squamous cell carcinoma. The results provided a novel understanding and an applicable pharmacogenomic tool for individualized management of cervical cancer patients.

  8. Primary herpes simplex virus infection mimicking cervical cancer.

    PubMed

    Tomkins, Andrew; White, Catherine; Higgins, Stephen Peter

    2015-06-02

    We report the case of an 18-year-old woman presenting with ulceration of the cervix caused by primary type 2 herpes simplex infection in the absence of skin lesions. The differential diagnosis included cervical cancer and we referred the patient for urgent colposcopy. However, laboratory tests proved the viral aetiology of the cervical ulceration and the cervix had healed completely 3 weeks later. The case highlights the need to consider herpes simplex infection in the differential diagnosis of ulceration of the cervix even when there are no cutaneous signs of herpes.

  9. Patient, Physician, and Nurse Factors Associated With Entry Onto Clinical Trials and Finishing Treatment in Patients With Primary or Recurrent Uterine, Endometrial, or Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Recurrent Cervical Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage I Uterine Corpus Cancer; Stage I Uterine Sarcoma; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Uterine Sarcoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Uterine Sarcoma; Stage IV Uterine Corpus Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  10. Carcinoma of unknown primary and paraneoplastic dermatomyositis

    PubMed Central

    Sonnenblick, Amir

    2015-01-01

    Dermatomyositis is known to be associated with neoplastic disorders, however the presentation of carcinoma of unknown primary as dermatomyositis is rare. We describe a case index of 50-year-old female who presented with enlarged inguinal lymph nodes accompanied with symmetric proximal muscle weakness and erythematous plaques. Conventional basic work-up did not reveal the diagnosis, however, positron emission tomography-computed tomography and re-staining of the pathology specimen suggested the ovaries as the primary site. Chemotherapy including carboplatin paclitaxel and bevacizumab led to complete response of disease and improvement in the dermatomyositis. The present case emphasizes the importance of a thorough directed evaluation for the underlying cancer in patients with carcinoma of unknown primary presenting as dermatomyositis. We further provide an up-to-date detailed review of published data describing these clinical entities. PMID:26677443

  11. [Study on molecular hybridization with biotin-labelled HPV 16 DNA probe in human cervical carcinoma].

    PubMed

    Li, Y; Huang, G Q; Mao, T; Huang, Y F; Xiao, H Y; Liu, B L

    1989-09-01

    Biotin-labelled human papillomavirus (HPV) 16 type DNA probe was prepared by the techniques of molecular biology. And dot hybridization technique was used to detect the HPV 16 homologous sequences in the tissues DNA of human cervical carcinoma. The results indicated that 16 cases out of 28 of the human cervical carcinoma tissues were positive. The positive rate was 57%. The other 4 cases of normal uterine cervix tissues were negative. Only 1 in 4 chronic cervicitis tissues showed positive. The HPV 16 plasmid DNA, as the positive control group, showed strong positive, while lambda-phage DNA was negative. The results have shown that the genome of the HPV actually exists in the tissue of the cervical carcinoma and that there is a close relationship between the cervical carcinoma and HPV infection. This experiment adopted the Biotin-labelled HPV 16 DNA probe. And it may provide us with a quick and sensitive method for investigation of the infection of HPV and its role in the carcinogenesis of cervical carcinoma. PMID:2560458

  12. Copper, zinc, and magnesium tissue and serum levels in patients with cervical carcinoma.

    PubMed

    Altintas, A; Vardar, M A; Gönlüsen, F; Atay, Y; Evrüke, C; Arpaci, A; Aridogan, N

    1995-01-01

    Serum and cervical tissue copper (Cu), zinc (Zn) and magnesium (Mg) levels were determined by atomic absorption spectrophotometry in 65 women with cervical carcinoma and compared with levels in 30 healthy women. The patients mean serum Cu level (184.8 +/- 12.3 mugr/dl) was significantly higher than the control group (p < 0.05). However, in relation to the control group, the differences in Mg, Zn and Cu levels in cancerous tissues of patients with cervical carcinoma were not statistically significant (p > 0.05). There was also no significant difference between FIGO Stage I and IIA patients according to their serum and tissue concentrations of these trace elements. We concluded that serum and tissue copper, zinc and magnesium determinations have no use in cervical carcinoma management.

  13. The landscape of alternative splicing in cervical squamous cell carcinoma

    PubMed Central

    Guo, Peng; Wang, Dan; Wu, Jun; Yang, Junjun; Ren, Tong; Zhu, Baoli; Xiang, Yang

    2015-01-01

    Background Alternative splicing (AS) is a key regulatory mechanism in protein synthesis and proteome diversity. In this study, we identified alternative splicing events in four pairs of cervical squamous cell carcinoma (CSCC) and adjacent nontumor tissues using RNA sequencing. Methods The transcripts of the four paired samples were thoroughly analyzed by RNA sequencing. SpliceMap software was used to detect the splicing junctions. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted to detect the alternative spliced genes-related signal pathways. The alternative spliced genes were validated by reverse transcription-polymerase chain reaction (RT-PCR). Results There were 35 common alternative spliced genes in the four CSCC samples; they were novel and CSCC specific. Sixteen pathways were significantly enriched (P<0.05). One novel 5′AS site in the KLHDC7B gene, encoding kelch domain-containing 7B, and an exon-skipping site in the SYCP2 gene, encoding synaptonemal complex 2, were validated by RT-PCR. The KLHDC7B gene with 5′AS was found in 67.5% (27/40) of CSCC samples and was significantly related with cellular differentiation and tumor size. The exon-skipping site of the SYCP2 gene was found in 35.0% (14/40) of CSCC samples and was significantly related with depth of cervical invasion. Conclusion The KLHDC7B and the SYCP2 genes with alternative spliced events might be involved in the development and progression of CSCC and could be used as biomarkers in the diagnosis and prognosis of CSCC. PMID:25565867

  14. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  15. Endothelin receptor blockade inhibits the growth of human papillomavirus-associated cervical carcinoma.

    PubMed

    Venuti, Aldo; Salani, Debora; Cirilli, Alessia; Simeone, Paola; Muller, Antonio; Flamini, Silvio; Padley, Robert; Bagnato, Anna

    2002-08-01

    Human papillomaviruses (HPVs) are associated with cervical cancer and interact with growth factors that may enhance malignant transformation of cervical carcinoma cells. Endothelin-1 (ET-1) is released from HPV-transfected keratinocytes and induces increased growth response in these cell lines in comparison with normal cells. HPV-positive cancer cells secrete ET-1 and express mRNA for ET-1 and its receptors, whereas HPV-negative carcinoma cell lines express only the ET(B) receptor (ET(B)R) mRNA and do not secrete ET-1. In HPV-positive cancer cells, ET(A)R mediates the ET-1-induced mitogenic effect and sustains the basal growth rate of unstimulated cervical tumour cells. Therefore, ET-1 may be involved in the neoplastic growth of HPV-associated cervical carcinoma, where the increased ET-1 autocrine loop can be targeted for antitumour therapy. In the present work, the action of specific antagonists of ET(A)R (BQ-123 and ABT-627), was analysed in CaSki and C33A cells that are derived from human cervical carcinoma. CaSki cells are HPV-16-positive, produce ET-1 and possess ET(A)R and ET(B)R, whereas the C33A line is HPV-negative, does not secrete ET-1 and has no ET(A)R. In HPV-positive cancer cells ABT-627 strongly inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated cervical tumour cells, whereas the ET(B)R antagonist had no effect. These results demonstrate that ET-1 participates in the progression of neoplastic growth in HPV-associated carcinoma, in which ET(A)R expression is increased and could be targeted for antitumour therapy. In conclusion, an ET-1 autocrine loop is involved in tumour cell proliferation via ET(A)R, and ABT-627 is effective in controlling proliferation of cervical carcinoma cells.

  16. The morbidity and utility of periaortic radiotherapy in cervical carcinoma

    SciTech Connect

    Potish, R.; Adcock, L.; Jones, T. Jr.; Levitt, S.; Prem, K.; Savage, J.; Twiggs, L.

    1983-02-01

    From 1971 through 1981, 81 women received 4350 to 5075 rad to the periaortic lymph nodes as part of their primary management for carcinoma of the uterine cervix. While two patients developed chronic small bowel damage, only one required surgical intervention. Five-year disease-free survival was 40%. Approximately one-third of the first recurrences were within the pelvic and periaortic radiation portals, with the remainder in the lungs, liver, bones, abdomen, and supraclavicular lymph nodes. Radiation dose and volume guidelines are presented in order to minimize enteric morbidity.

  17. [Report on 114 primary vaginal carcinomas].

    PubMed

    Sun, J H; Zhang, W H; Li, A L; Wu, A R

    1987-11-01

    114 patients with primary carcinoma of the vagina were treated in our hospital from 1958 to 1978. It accounted for 0.83% of all gynecological malignant tumors in the same period. The youngest was 26 years of age, the oldest 75. Patients 40-59 years comprised 61.4%. 33% of patients had wedding age under 17. 63.4% had more than 4 pregnancies and 58.4% gave more than 4 births. 89.69% was diagnosed as squamous cell carcinoma, 7.2% as adenocarcinoma, 2.06% as undifferentiated carcinoma and 1 as embryonic carcinoma. The tumor occurred frequently in the upper third and posterior wall of the vagina (60% and 68%). In this series, there were 21 stage I, 29 stage II, 61 stage III and 3 stage IV lesions. 110 patients were treated by radiotherapy in different schemes. Intracavitary radium or caesium plus 60Co external irradiation by four fields gave better result with a 5 year survival rate of 66.1%. Only 2 out of 12 patients were cured by 60Co rotation alone but if supplemented by intracavitary radium or caesium, the cure rate was increased. The 5 year survival rate was 71.4% for stage I, 62.1% for stage II, 42.6% for stage III and O for stage IV. After the radiotherapy, rectovaginal fistula developed in 1 patient, vesicovaginal fistula in 1. 14% was complicated with rectal bleeding and 8.18% with hematuria. PMID:3452544

  18. [Two autopsy cases of primary pituitary carcinoma].

    PubMed

    Negishi, K; Suzuki, T; Masuda, Y; Masugi, Y; Teramoto, A; Ohama, E

    1988-05-01

    We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Roles of galectin-7 and S100A9 in cervical squamous carcinoma: Clinicopathological and in vitro evidence.

    PubMed

    Zhu, Hong; Wu, Tian-Cong; Chen, Wei-Qiong; Zhou, Li-Jun; Wu, Yue; Zeng, Liang; Pei, Hai-Ping

    2013-03-01

    In our study, we for the first time assessed the association of galectin-7 and S100A9 with clinicopathological variables and survival outcomes in cervical squamous carcinoma patients and explored the underlying molecular mechanisms in cervical squamous carcinoma cell lines. Immunohistochemical analysis of 243 patient samples showed that the positive staining rate for galectin-7 and S100A9 gradually decreased from normal cervical tissue to intraepithelial neoplasia and to cervical squamous carcinoma. Both galectin-7 and S100A9 showed significant negative association with lymph node metastasis and staging of cervical squamous carcinoma. Cervical squamous carcinoma patients with negative staining of galectin-7 or S100A9 showed significantly lower 5-year overall survival rate than those with positive staining. Multivariate analysis with the Cox's proportional hazards model indicated that both galectin-7 and S100A9 had significant protective effect on cervical squamous carcinoma patients. Subsequent in vitro study in SiHa and C-33A human cervical squamous carcinoma cell lines revealed that knocking down galectin-7 or S100A9 enhanced tumor cell invasion and tumor cell viability against paclitaxel-induced apoptotic stress, likely through increasing the matrix metalloproteinase-9 expression and activating the phosphatidylinositol 3-kinase/Akt signaling pathway, respectively. Knocking down both galectin-7 and S100A9 produced a synergistic effect, with galectin-7 displaying more significant and consistent protective effects than S100A9 on cervical squamous carcinoma cells. In summary, our study for the first time provides clinicopathological and in vitro evidence showing that both galectin-7 and S100A9 play important protective roles in cervical squamous carcinoma, which provides fresh insights into the biology of cervical squamous carcinoma.

  20. Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.

    PubMed

    Yeasmin, Shamima; Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Ishikawa, Masako; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Otuski, Yoshiro; Kobayashi, Hiroshi; Nakayama, Satoru; Miyazaki, Kohji

    2012-04-01

    This study examined the biological and clinical significance of NAC1 (nucleus accumbens associated 1) expression in both cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1 amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1 expression was significantly correlated with shorter overall survival in squamous cell carcinomas (P < .0001). A multivariate analysis showed that positive NAC1 expression in squamous cell carcinomas was an independent prognostic factor for overall survival after standard radiotherapy (P = .0003). In contrast to squamous cell carcinomas, positive NAC1 expression did not correlate with shorter overall survival in adenocarcinomas/adenosquamous carcinomas (P = .317). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in the cervical cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These findings indicate that NAC1 overexpression is critical to the growth and survival of cervical carcinomas irrespective of histologic type. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression may benefit from a targeted therapy irrespective of histologic type.

  1. Langerhans Cell Histiocytosis of the Thyroid with Multiple Cervical Lymph Node Involvement Accompanying Metastatic Thyroid Papillary Carcinoma

    PubMed Central

    Ceyran, A. Bahar; Şenol, Serkan; Bayraktar, Barış; Özkanlı, Şeyma; Cinel, Z. Leyla; Aydın, Abdullah

    2014-01-01

    A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma. PMID:25349760

  2. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  3. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

    PubMed Central

    Qin, Xian; Wan, Yajun; Wang, Saiying; Xue, Min

    2016-01-01

    Background In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p) in human cervical carcinoma. Methods The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2), in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration. Results miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration. Conclusion The molecular pathway of miR-125a-5p/ABL2 plays an important role in human cervical carcinoma. Targeting miR-125a-5p/ABL2 pathway may provide a new treatment strategy for patients with cervical carcinoma. PMID:26766902

  4. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

    PubMed Central

    2012-01-01

    Background Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset of HPV

  5. Primary hyperparathyroidism due to parathyroid carcinoma.

    PubMed

    Mendoza, V; Hernández, A F; Márquez, M L; Delgadillo, M A; Peña, J; Mercado, M

    1997-01-01

    Most cases of primary hyperparathyroidism are due to either a parathyroid adenoma or to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established based on pathological criteria of vascular and capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We report the case of a middle-aged woman with a long standing history of nephrolithiasis, who presented with a palpable neck mass, weight loss, severe hypercalcemia and hypophosphatemia, as well as very high serum levels of intact parathyroid hormone. Surgical neck exploration revealed a large tumor that invaded trachea, esophagus, reccurrent laryngeal nerve, right apical pleura and right carotid artery. Pathological examination confirmed the invasive nature of the tumor. Along with the case report, we review the literature and discuss the diagnostic and therapeutic options of this rare condition.

  6. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  7. Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma: A Meta-Analysis

    PubMed Central

    Cheng, Ke-yan; Wang, Zhi-lian; Gu, Qian-yun; Hao, Min

    2016-01-01

    Objective Overexpression of survivin has been reported in many human tumors. However, the clinicopathological features associated with survivin overexpression in cervical carcinoma remain controversial. Thus, the current meta-analysis was performed to assess the clinicopathological significance of survivin in cervical carcinoma. Methods PubMed, EMBASE, and Web of Science databases were searched for relevant studies published through November 1, 2015. A meta-analysis was performed to evaluate the association between survivin expression and clinicopathological outcome in cervical carcinoma. Results Eleven eligible studies with a total of 865 patients were included. Survivin overexpression was closely related to lymph node metastasis (odds ratio [OR] = 0.679, 95% confidence interval [CI]: 0.509–0.905, P = 0.008) but was not significantly associated with tumor FIGO stage (I+II vs. III+IV) (OR = 0.843, 95% CI: 0.626–1.137, P = 0.264), tumor grade (G1+G2 vs. G3) (OR = 0.913, 95% CI: 0.689–1.210, P = 0.527), tumor size (>4 vs. ≤4 cm) (OR = 0.825, 95% CI: 0.434–1.570, P = 0.559), or stromal involvement (OR = 0.820, 95% CI: 0.545–1.233, P = 0.340). The correlation between survivin expression and overall survival was evaluated among a total of 238 patients from three eligible studies. The pooled HR was 1.129 (95% CI: 0.597–1.661; P = 0.000), indicating that survivin expression was significantly associated with poor survival in cervical carcinoma. Conclusions Based on the current meta-analysis, survivin is strongly associated with lymph node metastasis and poor prognosis. Additionally, survivin is a novel clinicopathological marker of cervical carcinoma and thus may be a therapeutic target for cervical carcinoma. PMID:27764228

  8. Expression and Prognostic Value of Aquaporin 1, 3 in Cervical Carcinoma in Women of Uygur Ethnicity from Xinjiang, China

    PubMed Central

    Chen, Rui; Shi, Yonghua; Amiduo, Reshalaity; Tuokan, Talaf; Suzuk, Lalai

    2014-01-01

    Background Overexpression of several aquaporins has been reported in different types of human cancer but the role of aquaporins in carcinogenesis has not yet been clearly defined. There is few report concerning role of aquaporins in human cervical carcinogenesis so far. Here, we determined the expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in Chinese women of Uygur ethnicity. Methods and Results Real-time PCR analyses demonstrated aquaporin 1, 3 mRNA were differentially expressed in cervical carcinoma, CIN 2-3 and mild cervicitis. Immunofluorescent and immunohistochemical analyses demonstrated aquaporin 1 was predominantly localized to stromal endothelial cells in cervical lesions. Aquaporin 3 was localized to the membrane of normal squamous epithelium, CIN and carcinoma cells. Aquaporin 1 and 3 were upregulated in cervical cancer compared to mild cervicitis and CIN2-3 (P<0.05); Tumor expression of aquaporin 1, 3 significantly increased in advanced stage disease, and patients with deeper tumor infiltration, lymph node metastases or larger tumor volume (P<0.05). Multivariate analysis demonstrated that aquaporin 1, 3 were not independent prognostic factors in cervical carcinoma. Conclusion Aquaporins may participate in the initiation and progression of cervical carcinoma by promoting tumor growth, invasion or lymph node metastasis. Further study is required to determine whether aquaporins have potential as prognostic factors in cervical cancer. PMID:24918928

  9. Primary oat cell carcinoma of the larynx

    SciTech Connect

    Aguilar, E.A. III; Robbins, K.T.; Stephens, J.; Dimery, I.W.; Batsakis, J.G.

    1987-02-01

    The aggressiveness of small (oat) cell carcinoma of the larynx presents a therapeutic challenge to the oncologist. Since the first description of this type of carcinoma in 1972, 52 patients have been reported in the literature and a variety of treatment regimens have been used. The purpose of this study was to report two new cases and review all previous reports to determine the disease's biological behavior, clinical manifestations, and optimum treatment. Thirty-five percent of the tumors were transglottic, and 27% were supraglottic. Fifty-four percent of patients had regional metastases at initial presentation and 17.6% had distant metastases. The median survival was 10 months for all patients. Patients who were treated with chemotherapy with or without other modalities had the best 2-year survival rates (52.2%). Forty-one percent of patients had regional recurrence only, 12.5% had regional recurrence and distant metastases, and 2% developed distant metastases only. We conclude that patients with oat cell carcinoma of the larynx should be treated with combination chemotherapy and radiation therapy. Surgery is best reserved for persistent and recurrent disease at the primary site and neck.

  10. Carcinomatous Meningitis from Unknown Primary Carcinoma

    PubMed Central

    Favier, L.; Ladoire, L.; Guiu, B.; Arnould, L.; Guiu, S.; Boichot, C.; Isambert, N.; Besancenot, J.F.; Muller, M.; Ghiringhelli, F.

    2009-01-01

    Carcinomatous meningitis (CM) occurs in 3 to 8% of cancer patients. Patients present with a focal symptom, and multifocal signs are often found following neurological examination. The gold standard for diagnosis remains the demonstration of carcinomatous cells in the cerebrospinal fluid on cytopathological examination. Despite the poor prognosis, palliative treatment could improve quality of life and, in some cases, overall survival. We report on a patient who presented with vertigo, tinnitus and left-sided hearing loss followed by progressive diffuse facial nerve paralysis. Lumbar cerebrospinal fluid confirmed the diagnosis of CM. However, no primary tumor was discovered, even after multiple invasive investigations. This is the first reported case in the English-language medical literature of CM resulting from a carcinoma of unknown primary origin. PMID:20737034

  11. Primary laryngeal cryptococcosis resembling laryngeal carcinoma.

    PubMed

    Tamagawa, Shunji; Hotomi, Muneki; Yuasa, Jun; Tuchihashi, Shigeki; Yamauchi, Kazuma; Togawa, Akihisa; Yamanaka, Noboru

    2015-08-01

    A case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. Histological examination showed pseudoepitheliomatous hyperplasia and severe submucosal inflammation with ovoid budding yeasts by Grocott's stain. A serological study indicated a high titer of cryptococcal antigen. After treating with oral fluconazole for 3 months, her primary lesion of larynx turned to be clear. We implicate a long-term use of steroids as the significant risk factor in developing cryptococcosis of the larynx.

  12. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    PubMed Central

    2012-01-01

    Background Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. Methods A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. Results We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). Conclusion As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited. PMID:23167826

  13. Transcriptomic and Functional Pathway Analysis of Human Cervical Carcinoma Cancer Cells Response to Microtubule Inhibitor

    PubMed Central

    Wang, Jin; Yan, Bin; Liu, Song-Mei; Sun, Huanhuan; Pan, Yonglong; Guan, Daogang; Zhang, Xiaoyan; Xu, Jianqing; Ma, Haiqing

    2015-01-01

    Background: There clearly is a need for effective chemotherapy for early-stage, high-risk patients with human cervical carcinoma. Vinblastine (VBL) is a key microtubule inhibitor, but unproven in its mechanisms as an important antitumor agent in cervical carcinoma. Methods: We selected the concentration of vinblastine inducing 30% cell death for analyses assessing the DNA content, gene expression and transcriptional gene regulation of VBL-treated KB-3 cells. Results: Transcriptomic and hierarchical clustering analysis demonstrated that treatment of KB-3 cells with VBL altered the expression of a diverse group of genes with G2/M arrest, which regulated by four oncogenic or tumor suppresser transcription factors (AP1, NFKB1, RELA, and TP53). Functional pathway analysis revealed the disease response to the biological effects of vinblastine in cervical carcinoma chemotherapy including protein ubiquitination pathway, RhoGDI signaling, integrin signaling, agranulocyte adhesion and biapedesis, and actin nucleation pathways. Northern blots also confirmed that KRT-7, FN14, IER3, and ID1 were deregulated in VBL-treated KB-3 cells. Conclusion: Transcriptional time series profiles and a functional pathway analysis of VBL-treated KB-3 cells will provide a new strategy for improving microtubule inhibitor chemotherapy for cervical carcinoma. PMID:26316889

  14. Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo

    PubMed Central

    SEKUŁA, MAŁGORZATA; MIEKUS, KATARZYNA; MAJKA, MARCIN

    2014-01-01

    Cervical carcinoma is frequently diagnosed among women, particularly in low and middle income countries. In this study, we investigated the role of the SDF-1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in vivo. Downregulation of CXCR4 receptor using an RNA interference system led to almost complete inhibition of the receptor expression, activation and function. CXCR4 receptor silencing led to decreased ability to signal, to induce migration and to form holoclone-like colonies, with no influence on viability/proliferation of the cells. CXCR4-deficient cells had also significantly lower levels of MMP-9. Interestingly, downregulation of CXCR4 expression resulted in reduced tumor growth in vivo. Tumors generated by CXCR4-deficient cells had also lower expression of the proliferation marker Ki-67 and decreased ability to engraft into lungs and spleen. Taken together, our results indicate that CXCR4 receptor may play an important role during cervical carcinoma invasion. In our study CXCR4 influenced invasive properties of cervical carcinoma cells both in vitro and in vivo. PMID:24728301

  15. Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

    PubMed Central

    Tonon, S A; Picconi, M A; Zinovich, J B; Liotta, D J; Bos, P D; Galuppo, J A; Alonio, L V; Ferreras, J A; Teyssié, A R

    1999-01-01

    OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence. PMID:10524669

  16. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-03-16

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  17. Concurrent chemoradiotherapy with nedaplatin in patients with stage IIA to IVA cervical carcinoma.

    PubMed

    Fujioka, Toru; Yasuoka, Toshiaki; Koizumi, Masae; Tanaka, Hiroki; Hashimoto, Hisashi; Nabeta, Motoo; Koizumi, Koji; Matsubara, Yuko; Hamada, Katsuyuki; Matsubara, Keiichi; Katayama, Tomihiro; Nawa, Akihiro

    2013-01-01

    The present study aimed to evaluate the efficacy and toxicities of nadaplatin-based concurrent chemoradiotherapy (CCRT) in patients with stage IIA to IVA cervical carcinoma. Patients with an International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA cervical carcinoma were treated with nadaplatin-based CCRT, using high-dose rate intracavitary brachytherapy (HDR-ICBT) or radiotherapy (RT) alone, in patients with FIGO stage IIA to IVA cervical carcinoma. CCRT with nedaplatin (80 mg/m(2)) was administered on Days 1 and 29. The records of 17 women treated either with nadaplatin-based CCRT using HSR-ICBT (n=8) or RT alone (n=9), for stage IIA to IVA cervical carcinoma were retrospectively reviewed. The activity and toxicity were compared in the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. The 5-year overall survival rates in the CCRT and RT groups were 68.6 and 77.8%, respectively. The median OS of the CCRT and RT groups was 38.5 and 27.3 months, respectively. There was no significant difference in either PFS (P=0.618) or OS (P= 0.231). The most common grade 3-4 or higher toxicities in the CCRT groups were leuko-/neutropenia (37.5%). The frequency of acute grade 3-4 toxicity was higher in the CCRT compared to the RT group. However, no statistically significant difference was observed. Nedaplatin-based CCRT was safely performed. Although the prognosis of patients with FIGO stage IIA to IVA cervical carcinoma was not significantly improved, fewer distant relapses were observed in this treatment. Consequently, nedaplatin-based CCRT may be considered as a potential alternative to cisplatin-based CCRT in this patient population.

  18. Preoperatively diagnosed case with co-existence of papillary thyroid carcinoma and cervical tuberculous lymphadenitis

    PubMed Central

    Ito, Taku; Saito, Hiroaki; Kishine, Naomi; Takeda, Takamori; Mizushima, Kota

    2015-01-01

    Introduction Papillary thyroid cancer (PTC) is the most frequent histological subtype of thyroid cancer. The lymph node metastasis is found in a high proportion of patients with PTC at the time of surgery. In contrast, tuberculous lymphadenitis remains a common cause of cervical lymphadenopathy in Asian countries. Presentation of case We present a 60-year-old woman with coexistence of papillary thyroid carcinoma (PTC) and cervical tuberculous lymphadenitis and to show the usefulness of fine-needle aspiration biopsy (FNAB) and quantiferon testing to distinguish a lymph node metastasis of PTC from tuberculous lymphadenitis. Discussion FNAB and quantiferon testing are useful tools to check if enlargement of cervical lymph node is due to tuberculous infection, and a surgical plan should be carefully determined to avoid unnecessary surgical complications and the spread of tuberculous infection. Conclusion The coexistence of cervical tuberculosis should be considered in the etiology of an enlarged lymph node for patients with PTC. PMID:26318132

  19. Orbital Metastasis of Cervical Carcinoma – Case Report and Review of Literature

    PubMed Central

    Arthur, Anupriya; Horo, Saban; Balasubramanian, Dhipak Arthur; Ram, Thomas Samuel; Peter, John Victor

    2016-01-01

    The orbit is a frequent site of metastasis, particularly from the breast, prostate gland and the lung. Carcinoma of the cervix metastasizing to the orbit is rare. We report a 27-year-old woman with Stage II B cervical cancer who presented with progressive painless protrusion of the left eye of one month duration associated with diplopia. Histology of the orbital mass was similar to that of the cervical cancer and reported as squamous cell carcinoma. She received palliative radiation to the left orbit 30 Gy in 10 fractions along with chemotherapy (Paclitaxel and Carboplatin). This resulted in regression of the proptosis. We review published literature of cases of carcinoma of the uterine cervix with metastasis to the orbit. PMID:26894102

  20. 77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... Therapies for Unresectable Primary Hepatocellular Carcinoma AGENCY: Agency for Healthcare Research and... local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g... Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma,...

  1. Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-06-18

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  2. Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  3. Uterine cervical carcinoma: role of matrix metalloproteinases (review).

    PubMed

    Libra, Massimo; Scalisi, Aurora; Vella, Nadia; Clementi, Silvia; Sorio, Roberto; Stivala, Franca; Spandidos, Demetrios A; Mazzarino, Clorinda

    2009-04-01

    Epidemiological and experimental studies have provided evidence that human papillomavirus (HPV) infection is a main player in the development of uterine cervical neoplasms. Migration of cancer cells from the origin tissue to surrounding or distant organs is essential for tumor progression. Many studies of tumor invasion and metastases have focused on the degradation of the extracellular matrix where matrix metalloproteinases (MMPs) play a central role. Two of these enzymes, MMP-2 and MMP-9, have been correlated with the processes of tumor cell invasion and metastasis in human cancers, including uterine neoplasms. It has been shown that the up-regulation of MMPs is associated with progression of cervical uterine neoplasms. This review describes the current understanding of MMP-2 and MMP-9 expression and activity in pre-cancer and cancer lesions of cervical uterine, which may open new strategies for diagnostic and therapeutic interventions.

  4. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

    PubMed

    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a

  5. FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

    ClinicalTrials.gov

    2015-06-03

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  6. Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer.

    PubMed

    Diaz, Daniel; Delgadillo, Dulce Maria; Hernández-Gallegos, Elizabeth; Ramírez-Domínguez, Martha Eugenia; Hinojosa, Luz María; Ortiz, Cindy Sharon; Berumen, Jaime; Camacho, Javier; Gomora, Juan Carlos

    2007-02-01

    Cervical cancer (CaC) is the third most frequent cause of death from cancer among women in the world and the first in females of developing countries. Several ion channels are upregulated in cancer, actually potassium channels have been suggested as tumor markers and therapeutic targets for CaC. Voltage-gated sodium channels (VGSC) activity is involved in proliferation, motility, and invasion of prostate and breast cancer cells; however, the participation of this type of channels in CaC has not been explored. In the present study, we identified both at the molecular and electrophysiological level VGSC in primary cultures from human cervical carcinoma biopsies. With the whole cell patch clamp technique, we isolated and identified a voltage-gated Na(+) current as the main component of the inward current in all investigated cells. Sodium current was characterized by its kinetics, voltage dependence, sensitivity to tetrodotoxin (TTX) block and dependence to [Na(+)](o). By analyzing the expression of mRNAs encoding TTX-sensitive Na(+) channel alpha subunits with standard RT-PCR and specific primers, we detected Na(v)1.2, Na(v)1.4, Na(v)1.6, and Na(v)1.7 transcripts in total RNA obtained from primary cultures and biopsies of CaC. Restriction enzyme analysis of PCR products was consistent with the molecular nature of the corresponding genes. Notably, only transcripts for Na(v)1.4 sodium channels were detected in biopsies from normal cervix. The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer.

  7. A prospective study of the relationship between prediagnostic human papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas.

    PubMed

    Sigstad, E; Lie, A K; Luostarinen, T; Dillner, J; Jellum, E; Lehtinen, M; Thoresen, S; Abeler, V

    2002-07-15

    Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2-8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA.

  8. Primary hepatic sarcomatoid carcinoma: A case report

    PubMed Central

    LENG, QIANYING; XIANG, XI; TANG, YUANJIAO; YANG, YUJIA; QIU, LI

    2015-01-01

    Sarcomatoid carcinoma (SC) is a malignant tumor type of unclear pathogenesis, which rarely occurs in the liver. The present study reports the case of a 60-year-old woman who presented with multiple masses in her liver, with no fever, abdominal pain or jaundice. Serological markers for hepatitis B and C virus were negative, as was the test for α fetoprotein. Abdominal enhanced magnetic resonance imaging examination confirmed multiple lesions in the liver, and liquefactive necrosis was observed. The patient underwent a right hepatectomy, in addition to a cholecystectomy. Cytokeratin 8 (CK8), cluster of differentiation 117, pancytokeratin and vimentin were positively detected using immunohistochemistry, and thus the diagnosis of primary hepatic SC (PHSC) was established. During the follow-up period, characteristic imaging manifestations of tumor recurrence were detected, including peripheral enhancement, central necrosis, variable enhancement, venous invasion and intrahepatic metastasis. The immunohistochemical detection of CK, epithelial membrane antigen and vimentin, with CK8 as a critical indicator, may be useful for the diagnosis of PHSC. The preferred treatment for PHSC is surgical resection and the prognosis is poor. PMID:26622454

  9. [Carcinoma of unknown origin++ with latero-cervical metastasis. Diagnostic problems. Retrospective analysis of 110 cases of latero-cervical tumefaction].

    PubMed

    Santacroce, L; Luperto, P; Fiorella, M L; Losacco, T

    2000-01-01

    The cervical region, despite to its little extension, is very important by the surgical and anatomical point of view. This region, occupied by a lot of organs, sometimes is the site of metastasis from carcinomas located in various parts of the body. In some cases the origin site of cancer stays unknown. The aim of this paper is the retrospective analysis of 110 cases of latero cervical swellings and the related problems of differential diagnosis.

  10. Carcinoma of the cervical stump: comparison of radiation therapy factors, survival and patterns of failure with carcinoma of the intact uterus

    SciTech Connect

    Igboeli, P.; Kapp, D.S.; Lawrence, R.; Schwartz, P.E.

    1983-02-01

    Eighty-nine patients with previously untreated invasive carcinoma of the cervical stump were seen at Yale-New Haven Hospital from 1953 through 1977. This represented 9.4% of the carcinomas of the cervix seen during this time period. Eighty-five of the 89 patients (95.5%) had ''true'' cancers of the cervical stump diagnosed 2 years or more after subtotal hysterectomy, while 4 of the 89 patients (4.5%) had ''coincident'' cancers diagnosed within 2 years of the subtotal hysterectomy. All cervical cancers were staged by the F.I.G.O. classification. Patient characteristics, methods of management, failure sites and survival of patients with carcinoma of the cervical stump were compared to those patients with carcinoma in the intact uterus. Patients with cervical stump cancers were treated in a similar manner to those with carcinomas of the intact uterus, using a combination of external beam irradiation and intracavitary radium. The stump cancer patients had a similar stage distribution to the patients with cancers of the intact uterus but, on the average, they were older and received less irradiation. The patterns of failure were similar on a stage for stage basis, but the survival and disease-free survival for stump cancer patients were superior to those of the patients with carcinoma of the intact uterus.

  11. Papillary thyroid carcinoma involving cervical neck lymph nodes: correlations with lymphangiogenesis and ultrasound features.

    PubMed

    Choi, Yoonjung; Park, Kyung Joo; Ryu, Seungho; Kim, Dong-Hoon; Yun, Jisup; Kang, Doo Kyoung; Chun, Mison

    2012-01-01

    Stratification of risk factors for cervical lymph node metastasis (LNM) in thyroid papillary carcinoma is important for providing standards for post-operative adjuvant radio-iodine therapy and for patient prognosis. We investigated pathological factors based on the lymphatic vessel system and radiological features associated with tumor with cervical neck LNM. Among patients who had undergone thyroidectomy confirmed to be papillary thyroid carcinoma, we selected 126 age-sex matched paired patients without cervical LNM (group 1) and with LNM (group 2) to evaluate risk factors. Pathological factors evaluated were size, multiplicity, and extra thyroid extension state, based on the pathological reports using stored data. The lymphatic vessel density (LVD) of each tumor was evaluated by staining for VEGFR-3 and D2-40 and correlated with cervical LNM state. Malignant ultrasound features were evaluated to compare the differences between these two groups. Larger tumor size, multiplicity, extrathyroid extension were more common in group 2 (p<0.05). The median percentage of VEGFR-3 for group 1 was 20 (range 0-30) and D2-40 was 13 (range 7-23) while for group 2, VEGFR-3 was 80 (70-90) and D2-40 was 78 (54-114). LVD measured by intratumoral D2-40 staining was 20.6% and 79.4% for group 1 and group 2, respectively. Intra-tumoral lymphatics measured by D2-40 stain had a strong correlation with cervical LNM (Odds 1.230, CI 1.01.-1.499 p value 0.040). Ultrasound (US) features had no significant differences between the two groups although calcifications tended to be higher in group 2 (84% vs. 76% p=0.264). Lymphatic vessel density and nodule echogenicity were not associated with LNM. Intratumoral lymphangiogenesis was most strongly associated with LNM and thus, could be a useful predictive marker for cervical LNM.

  12. Prognostic Value of Baseline Lymphocyte Count in Cervical Carcinoma Treated With Concurrent Chemoradiation

    SciTech Connect

    Choi, Chel Hun; Kang, Heeseok; Kim, Woo Young; Kim, Tae-Joong; Lee, Jeong-Won; Huh, Seung Jae; Lee, Je-Ho; Kim, Byoung-Gie; Bae, Duk-Soo

    2008-05-01

    Purpose: This study examined factors predicting tumor response and progression-free survival in patients with locally advanced cervical carcinoma treated with concurrent chemoradiation (CCRT). Methods and Materials: Medical records of 143 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics Stage IB2 to IVA) treated with CCRT were reviewed. Univariate and multivariate analyses were used to retrospectively evaluate prognostic factors, including baseline lymphocyte count, that affect tumor response and progression-free survival. Results: Of the variables evaluated, greater baseline lymphocyte count was the factor most predictive of a complete clinical response, followed by smaller tumor size (p = 0.003 and p = 0.007, respectively). Multivariate analysis showed baseline lymphocyte count, which was treated as a continuous variable with every 1 x 10{sup 9} lymphocytes/L, to remain a prognostic factor with an odds ratio of 3.08 (95% confidence interval, 1.31-7.23). In addition, a statistically significant association (p = 0.023) was found between baseline lymphocyte count and progression-free survival, with a hazard ratio of 0.42 (95% confidence interval, 0.20-0.89) in the Cox proportional hazards model. Conclusions: Despite the small number of patients and possible biologic variation existing in lymphocyte subset number and activity, these findings highlight the strong prognostic value of baseline lymphocyte count in patients with locally advanced cervical carcinoma treated with CCRT. Therefore, a larger number of patients and analysis of lymphocyte subsets are needed.

  13. Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

    SciTech Connect

    Huang, Hanhui; Zhao, Wenrong; Yang, Dan

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

  14. High-risk human papilloma virus genotypes in cervical carcinoma of Serbian women: Distribution and association with pathohistological findings.

    PubMed

    Stamenković, Miodrag; Knežević, Aleksandra; Knežević, Ivana; Kuzmanović, Igor; Karalić, Danijela; Milenković, Sanja; Jovanović, Tanja

    2016-09-01

    A significant role of high-risk Human papilloma viruses (HR HPV) in the development of cervical carcinoma is well known. HR HPV 16 and 18 account for approximately 70% of all cases of cervical cancer worldwide. The incidence of cervical cancer in Serbia, is one of the highest in Europe. The aim of our study was to investigate the distribution of HR HPV types in cervical carcinoma of Serbian women, as well as association between the HPV types and pathohistological findings. The study included 80 archival cervical cancer tissues from the same number of patients. The presence of HPV DNA was determined using MY09/MY11 primers for L1 gene and GP1/GP2 primers for E1 gene. HPV was detected in 78.75% tissues. HR HPV genotypes found in the decreasing order of frequency were: HPV16 (80.39%), HPV33 (7.84%), HPV58 (5.88%), HPV18 (1.96%), HPV45 (1.96%) and HPV53 (1.96%). The examined tissues were 91.25% squamous cell carcinomas and 8.75% adenocarcinoma. The high frequency of HPV 16 was observed in both types of carcinoma (80.8% and 75%, respectively) while the prevalence of HPV18 was low. These results may contribute to the implementation of cervical carcinoma prevention program in Serbia, including the selection of the most appropriate vaccine and immunization program. PMID:27461126

  15. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2016-09-19

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  16. Stereotactic Body Radiotherapy for Primary Hepatocellular Carcinoma

    SciTech Connect

    Andolino, David L.; Johnson, Cynthia S.; Maluccio, Mary; Kwo, Paul; Tector, A. Joseph; Zook, Jennifer; Johnstone, Peter A.S.; Cardenes, Higinia R.

    2011-11-15

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). Methods and Materials: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. Results: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no {>=}Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. Conclusions: SBRT is a safe, effective, noninvasive option for patients with HCC {<=}6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.

  17. Prognosis of Cervical Cancer in the Era of Concurrent Chemoradiation from National Database in Korea: A Comparison between Squamous Cell Carcinoma and Adenocarcinoma

    PubMed Central

    Lee, Jung-Yun; Kim, Young Tae; Kim, Sunghoon; Lee, Boram; Lim, Myong Cheol; Kim, Jae-Weon; Won, Young-Joo

    2015-01-01

    In 1999, the National Cancer Institute issued a clinical advisory strongly touting the advantage of cisplatin-based chemoradiation (CCRT) for cervical cancer patients requiring radiation for their treatment. This study aimed to compare survival outcomes of cervical squamous cell carcinoma and adenocarcinoma before and after the advent of CCRT. Data were obtained from the Korea National Cancer Incidence Database for patients who were diagnosed with cervical cancers between 1993 and 2012. We compared survival according to histologic subtypes in cervical cancer patients diagnosed before (1993–1997), during (1998–2002), and after (2003–2012) the introduction of CCRT. A total of 80,766 patients were identified, including 64,531 (79.9%) women with squamous cell carcinomas and 7,265 (9.0%) with adenocarcinoma. With the introduction of CCRT, survival trends gradually increased in patients of both histologic subtypes with regional tumors. However, survival was significantly higher in squamous cell carcinoma than in adenocarcinoma patients regardless of treatment modalities (surgery alone, P < 0.001; surgery followed by CCRT, P < 0.001; or primary CCRT, P = 0.003). Multivariate analysis showed that adenocarcinoma was an independent negative prognostic factor for survival regardless of the time period (before CCRT, hazard ratio (HR) = 1.49; 95% confidence interval (CI), 1.37–1.62; after introduction of CCRT, HR = 1.40; 95% CI, 1.30–1.50). Although the survival of adenocarcinoma has improved after the introduction of CCRT, adenocarcinoma is still associated with worse overall survival compared to squamous cell carcinoma in the era of CCRT. PMID:26660311

  18. Precise Classification of Cervical Carcinomas Combined with Somatic Mutation Profiling Contributes to Predicting Disease Outcome

    PubMed Central

    Spaans, Vivian M.; Trietsch, Marjolijn D.; Peters, Alexander A. W.; Osse, Michelle; ter Haar, Natalja; Fleuren, Gert J.; Jordanova, Ekaterina S.

    2015-01-01

    Introduction Squamous cell carcinoma (SCC), adenocarcinoma (AC), and adenosquamous carcinoma (ASC) are the most common histological subtypes of cervical cancer. Differences in the somatic mutation profiles of these subtypes have been suggested. We investigated the prevalence of somatic hot-spot mutations in three well-defined cohorts of SCC, AC, and ASC and determined the additional value of mutation profiling in predicting disease outcome relative to well-established prognostic parameters. Materials and Methods Clinicopathological data were collected for 301 cervical tumors classified as SCC (n=166), AC (n=55), or ASC (n=80). Mass spectrometry was used to analyze 171 somatic hot-spot mutations in 13 relevant genes. Results In 103 (34%) tumors, 123 mutations were detected (36% in SCC, 38% in AC, and 28% in ASC), mostly in PIK3CA (20%) and KRAS (7%). PIK3CA mutations occurred more frequently in SCC than AC (25% vs. 11%, P=0.025), whereas KRAS mutations occurred more frequently in AC than SCC (24% vs. 3%, P<0.001) and ASC (24% vs. 3%, P<0.001). A positive mutation status correlated with worse disease-free survival (HR 1.57, P=0.043). In multivariate analysis, tumor diameter, parametrial infiltration, and lymph node metastasis, but not the presence of a somatic mutation, were independent predictors of survival. Conclusion Potentially targetable somatic mutations occurred in 34% of cervical tumors with different distributions among histological subtypes. Precise classification of cervical carcinomas in combination with mutation profiling is valuable for predicting disease outcome and may guide the development and selection of tumor-specific treatment approaches. PMID:26197069

  19. The three most common human papillomavirus oncogenic types and their integration state in Thai women with cervical precancerous lesions and carcinomas.

    PubMed

    Aromseree, Sirinart; Chaiwongkot, Arkom; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Patarapadungkit, Natcha; Pientong, Chamsai

    2014-11-01

    To understand the potential role in cervical cancer development of the three most common high-risk human papillomavirus (HR-HPVs) in Thai women, HPV genotypes and viral genome statuses in different cervical lesions were investigated. Cervical tissues consisting of no cervical intraepithelial neoplasia (84 cases), grade I cervical intraepithelial neoplasia (176 cases), grade II-III cervical intraepithelial neoplasia (91 cases), and squamous cell carcinoma (66 cases) were subjected for HPV genotyping by polymerase chain reaction (PCR) and reverse line blot hybridization assay and for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay. HPV prevalence was 28.6% in no cervical intraepithelial neoplasia, 40.3% in grade I cervical intraepithelial neoplasia, 70.3% in grade II-III cervical intraepithelial neoplasia and 86.4% in squamous cell carcinoma cases. The three most common HR-HPV types were HPV 16, 58, and 18 which were distributed in all cervical lesions. HPV physical statuses could be investigated in 4 no cervical intraepithelial neoplasias, 2 grade I cervical intraepithelial neoplasias, 28 grade II-III cervical intraepithelial neoplasias and 31 squamous cell carcinomas. The integrated-derived transcripts were found 3.6% in grade II-III cervical intraepithelial neoplasia and 48.4% in squamous cell carcinoma, whereas no viral genome integration was found in the group of no cervical intraepithelial neoplasia or grade I cervical intraepithelial neoplasia samples. The frequencies of HR-HPV integration in squamous cell carcinoma were found 40%, 100%, 20% of HPV 16, 18, and 58. This study indicates the oncogenic potential ability of the three most common HR-HPVs associated with cervical cancer progression.

  20. HPV vaccination: The most pragmatic cervical cancer primary prevention strategy.

    PubMed

    Sankaranarayanan, Rengaswamy

    2015-10-01

    The evidence that high-risk HPV infections cause cervical cancers has led to two new approaches for cervical cancer control: vaccination to prevent HPV infections, and HPV screening to detect and treat cervical precancerous lesions. Two vaccines are currently available: quadrivalent vaccine targeting oncogenic HPV types 16, 18, 6, and 11, and bivalent vaccine targeting HPV 16 and 18. Both vaccines have demonstrated remarkable immunogenicity and substantial protection against persistent infection and high-grade cervical cancer precursors caused by HPV 16 and 18 in HPV-naïve women, and have the potential to prevent 70% of cervical cancers in adequately vaccinated populations. HPV vaccination is now implemented in national programs in 62 countries, including some low- and middle-income countries. The early findings from routine national programs in high-income countries are instructive to encourage low- and middle-income countries with a high risk of cervical cancer to roll out HPV vaccination programs and to introduce resource-appropriate cervical screening programs.

  1. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

    PubMed

    Fan, Xiaobin; Wu, Weiguang; Shi, Haixia; Han, Jianqiu

    2013-07-01

    Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

  2. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  3. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  4. Correlation between histological grade and positron emission tomography parameters in cervical carcinoma

    PubMed Central

    Mocciaro, Vanessa; Scollo, Paolo; Stefano, Alessandro; Gieri, Stefania; Russo, Giorgio; Scibilia, Giuseppe; Cosentino, Sebastiano; Murè, Gabriella; Baldari, Sara; Sabini, Maria Gabriella; Fraggetta, Filippo; Gilardi, Maria Carla; Ippolito, Massimo

    2016-01-01

    The aim of the present study was to evaluate the changes in cervical cancer glucose metabolism for different levels of cellular differentiation. The metabolic activity was measured by standardized uptake value (SUV), SUV normalized to lean body mass, metabolic tumor volume and total lesion glycolysis using fluorine-18 fluorodeoxyglucose positron emission tomography (PET). A correlation study of these values could be used to facilitate therapeutic choice and to improve clinical practice and outcome. This study considered 32 patients with diagnosed cervical cancers, at different International Federation of Gynecology and Obstetrics stages. Glucose metabolism was assessed by PET examination, and histological specimens were examined to determine their initial grade of differentiation. A correlation study of these values was evaluated. Histological examination showed that all cases were of squamous cell carcinoma. Regarding the differentiation of the tumor, 19 well- to moderately-differentiated tumors and 13 poorly-differentiated tumors were determined. Negative findings for correlations between metabolic parameters and initial grade of histological differentiation were found, and considering that histological grade has been shown to have no consistent prognostic value in cervical cancer treatment, PET imaging could play a significant role in cervical cancer prognosis. PMID:27446445

  5. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines

    SciTech Connect

    Scheffner, M.; Muenger, K.; Byrne, J.C.; Howley, P.M. )

    1991-07-01

    Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.

  6. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  7. Alterations of chromosome 11q13 in cervical carcinoma cell lines

    SciTech Connect

    Popescu, N.C.; Zimonjic, D.B.

    1996-02-01

    In cervical cancer, evidence for the existence of a tumor-suppressor gene on chromosome 11 has been generated from studies with somatic cell hybrids, chromosome microcell transfer, or deletion analysis of DNA markers. As suggested by somatic cell hybrids analysis, chromosome 11 harbors at least three distinctive tumor-suppressor genes, two on the short arm and one on the long arm. Loss of heterozygosity (LOH) analysis using 16 markers, 10 of which were microsatellite-based, placed the region of a putative tumor-suppressor gene to 11q22-24. Recently, 11q13 was assigned as another possible site on the basis of molecular rearrangements, deletions, and translocations, nonrandomly involving this region in four of eight cervical carcinoma cell lines. Abnormal chromosomes 11 were found in HeLa, SiHa, and Caski lines and in C33A, a human papilloma virus-negative cell line. 18 refs.

  8. Tattoo-pigmented cervical lymph node that masqueraded as the sentinel lymph node in oral squamous cell carcinoma.

    PubMed

    Pinto, Amith; Wieshmann, Hulya; Triantafyllou, Asterios; Shaw, Richard

    2015-11-01

    We describe a case of a pigmented cervical lymph node mimicking the sentinel node during sentinel lymph node biopsy (SLNB) on a patient with oral squamous cell carcinoma (OSCC). The patient had extensive tattoos on his neck. This pigmented lymph node was not identified to be the sentinel lymph node using static and dynamic lymphoscintigraphy. Subsequent histological analysis revealed tattoo pigment within this lymph node. It is important during cervical SLNB to be aware that cutaneous tattoos can pigment lymph nodes. PMID:26188933

  9. Human Papillomavirus and Epstein-Barr virus co-infection in Cervical Carcinoma in Algerian women

    PubMed Central

    2013-01-01

    Background Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood. Methods Fifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively. Results HR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively. Conclusion The high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation. PMID:24252325

  10. Primary cutaneous mucoepidermoid carcinoma infiltrating the parotid gland.

    PubMed

    Minni, A; Roukos, R; De Carlo, A; Di Tillo, G; Illuminati, G; Gallo, P

    2012-10-01

    Mucoepidermoid carcinoma (MEC) of the skin is an extremely rare neoplasm but is common in the major and minor salivary glands accounting of approximately 30% of all malignant tumors arising from these glands. Cutaneous involvement should be carefully assessed to exclude the possibility of metastases from distant sites. We report an 81 year-old man presenting a primary cutaneous mucoepidermoid carcinoma infiltrating his left parotid gland. Excision of the affected skin and a total parotidectomy with supraomohyoid neck dissection (level I-III) was performed followed by radiotherapy. No relapse after 2 years follow up has been observed. Since the primary cutaneous mucoepidermoid carcinoma is an aggressive neoplasm that frequently develops metastases it is important to distinguish it from primary MEC originating from the salivary glands for better management and suitable therapeutic decisions.

  11. Primary cutaneous mucoepidermoid carcinoma infiltrating the parotid gland.

    PubMed

    Minni, A; Roukos, R; De Carlo, A; Di Tillo, G; Illuminati, G; Gallo, P

    2012-10-01

    Mucoepidermoid carcinoma (MEC) of the skin is an extremely rare neoplasm but is common in the major and minor salivary glands accounting of approximately 30% of all malignant tumors arising from these glands. Cutaneous involvement should be carefully assessed to exclude the possibility of metastases from distant sites. We report an 81 year-old man presenting a primary cutaneous mucoepidermoid carcinoma infiltrating his left parotid gland. Excision of the affected skin and a total parotidectomy with supraomohyoid neck dissection (level I-III) was performed followed by radiotherapy. No relapse after 2 years follow up has been observed. Since the primary cutaneous mucoepidermoid carcinoma is an aggressive neoplasm that frequently develops metastases it is important to distinguish it from primary MEC originating from the salivary glands for better management and suitable therapeutic decisions. PMID:23090800

  12. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

    PubMed

    Choi, Y-W; Bae, S M; Kim, Y-W; Lee, H N; Kim, Y W; Park, T C; Ro, D Y; Shin, J C; Shin, S J; Seo, J-S; Ahn, W S

    2007-01-01

    Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

  13. c-Myc protein expression is not an independent prognostic predictor in cervical squamous cell carcinoma.

    PubMed

    Brenna, S M F; Zeferino, L C; Pinto, G A; Souza, R A; Andrade, L A L; Vassalo, J; Martinez, E Z; Syrjanen, K J

    2002-04-01

    The c-myc protein is known to regulate the cell cycle, and its down-regulation can lead to cell death by apoptosis. The role of c-myc protein as an independent prognostic determinant in cervical cancer is controversial. In the present study, a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and III (21, 28 and 51%, respectively) cervical squamous cell carcinomas was analyzed for c-myc protein expression using immunohistochemistry. The disease-free survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival analysis for 116 women who completed the standard FIGO treatment and were followed up for 5 years. Positive c-myc staining was detected in 40% of carcinomas, 29% being grade 1, 9% grade 2, and 2% grade 3. The distribution of positive c-myc according to FIGO stage was 19% (17 women) in stage I, 33% (29) in stage II, and 48% (43) in stage III of disease. During the 60-month follow-up, disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women) was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6% at 12, 36, and 60 months, respectively (not significant). The present data suggest that immunohistochemical demonstration of c-myc does not possess any prognostic value independent of FIGO stage, and as such is unlikely to be a useful prognostic marker in cervical squamous cell carcinoma.

  14. Results of radiation therapy in stage 1B cervical carcinoma at King Chulalongkorn Memorial Hospital: fifteen-year experience.

    PubMed

    Lertbutsayanukul, C; Lertsanguansinchai, P; Shotelersuk, K; Khorprasert, C; Rojpornpradit, P; Asavametha, N; Pataramontree, J; Suriyapee, S; Tresukosol, D; Termrungruanglert, W

    2001-06-01

    A retrospective study was performed on 131 patients with stage 1B cervical carcinoma who were referred and treated with external beam radiation and intracavitary brachytherapy at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between February 1985 and February 2000. Primary outcomes were overall survival rate, progression free survival rate, recurrence, and treatment-related complications. The treatment results from different sources of intracavitary radiation therapy were secondary endpoints. The number of patients treated with Ra-226, Cs-137, and Ir-192 intracavitary irradiation were 12, 84, and 35 patients respectively. The median follow-up times were 69, 59, and 21 months for Ra-226, Cs-137, and Ir-192, respectively. Actuarial 5-year overall survival rate was 89 per cent. The 5-year progression free survival rate was 80 per cent. Actuarial 5-year survival and progression free survival rate were comparable among different sources of intracavitary brachytherapy (p = 0.553 and p=0.793, respectively). The overall recurrent rate was 16.8 per cent. Of the recurrence; 40.9 per cent was locoregional, 54.6 per cent was distant failure, and 4.5 per cent was combined locoregional and distant failure. The overall complication rate was 25.95 per cent. The severe complication rates (Grade III-V) from treatment occurred in the urinary bladder (0.76%) and in the small bowel (0.76%.) These results suggest that radiation therapy alone is an effective treatment for stage 1B cervical carcinoma. Additionally, all types of intracavitary brachytherapy provide comparable clinical results.

  15. Intensity-Modulated Radiotherapy for Cervical Lymph Node Metastases From Unknown Primary Cancer

    SciTech Connect

    Madani, Indira Vakaet, Luc; Bonte, Katrien; Boterberg, Tom; Neve, Wilfried de

    2008-07-15

    Purpose: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). Methods and Materials: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy between August 1994 and October 2003. Results: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). Conclusions: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.

  16. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance.

    PubMed

    Xu, Xiao-Xian; Zhou, Jian-Song; Yuan, Shu-Hui; Yu, Hua; Lou, Han-Mei

    2015-09-01

    Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine.

  17. Sexual function after surgical and radiation therapy for cervical carcinoma

    SciTech Connect

    Seibel, M.; Freeman, M.G.; Graves, W.L.

    1982-10-01

    One hundred women treated for carcinoma of the cervix were interviewed more than one year later to establish the effects of radiation or surgical therapy on sexual function. Forty-three had received irradiation, 44 nonradical surgery, six combined surgery and irradiation, and seven radical surgery. The irradiation and nonradical surgery groups were each further subdivided into subgroups of patients aged 30 to 49 for age-controlled comparison. Patients in the irradiation group had statistically significant decreases in sexual enjoyment, ability to attain orgasm, coital opportunity, frequency of intercourse, and coital desire. The group who had nonradical surgical procedures had no significant change in sexual function after treatment. Similar results were found in both age-controlled subgroups, eliminating age as a major etiologic factor. Marked vaginal alterations were recorded in the majority of irradiated patients, but were not present among the groups treated with nonradical surgery. The vaginal changes alone could not be held accountable for the significant decrease in sexual function among women who received pelvic irradiation. The origin of decreased sexual desire after radiation therapy is complex, and not yet completely understood. We propose therapeutic programs to help women deal with the emotional and physical consequences of pelvic irradiation.

  18. Male pelvic squamous cell carcinoma of unknown primary origin.

    PubMed

    Chiec, Lauren; Verma, Sadhna; Kendler, Ady; Abdel Karim, Nagla

    2014-01-01

    Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelvis demonstrated a large mass in his retroperitoneum. The mass was determined to be squamous cell carcinoma of unknown primary origin. Additionally, the patient had small nodules in his right lower lung lobe and right hepatic lobe. The patient was treated with concomitant chemoradiation, including cisplatin and intensity-modulated radiation therapy, followed by carboplatin and paclitaxel. The patient achieved partial remission, in which he remained one year after his presentation. Our case is consistent with the literature which suggests that squamous cell carcinoma of unknown primary origin occurring outside of the head and neck region may have a more favorable prognosis than other carcinomas of unknown primary origin. Further studies are necessary to determine the most appropriate work-up, diagnosis, and optimal treatment strategies. PMID:25478265

  19. Cervical lymph node metastasis in chromophobe renal cell carcinoma: a case report and review of the literature.

    PubMed

    Bouadel, Noureddine; El Ayoubi, Fahd; Bennani-Baiti, A Anass; Benbouzid, Mohamed Anas; Essakalli, Leila; Kzadri, Mohammed; El Ayoubi, Ali

    2013-01-01

    The metastasis of chromophobe renal cell carcinoma to head and neck region, described herein, has never been reported before to our knowledge. A 56-year-old woman with a history of nephrectomy, that revealed chromophobe renal cell carcinoma six years before, presented left cervical mass. Imaging showed with left cervical lymphadenopathies and thyroid nodule. Surgery with histopathological examination confirmed that it was a left central and lateral jugular lymph node metastasis of chromophobe renal cell carcinoma treated postoperatively by antiangiogenic therapy. The patient was successfully treated by surgery and antiangiogenic drugs with stabilization and no recurrence of the metastatic disease. The case and the literature reported here support that chromophobe renal cell carcinoma can metastasize to the head and neck region and should preferentially be treated with surgery and antiangiogenic therapy because of the associated morbidity and quality-of-life issues. PMID:24187640

  20. Cervical Lymph Node Metastasis in Chromophobe Renal Cell Carcinoma: A Case Report and Review of the Literature

    PubMed Central

    Bouadel, Noureddine; El Ayoubi, Fahd; Bennani-Baiti, A. Anass; Benbouzid, Mohamed Anas; Essakalli, Leila; Kzadri, Mohammed; El Ayoubi, Ali

    2013-01-01

    The metastasis of chromophobe renal cell carcinoma to head and neck region, described herein, has never been reported before to our knowledge. A 56-year-old woman with a history of nephrectomy, that revealed chromophobe renal cell carcinoma six years before, presented left cervical mass. Imaging showed with left cervical lymphadenopathies and thyroid nodule. Surgery with histopathological examination confirmed that it was a left central and lateral jugular lymph node metastasis of chromophobe renal cell carcinoma treated postoperatively by antiangiogenic therapy. The patient was successfully treated by surgery and antiangiogenic drugs with stabilization and no recurrence of the metastatic disease. The case and the literature reported here support that chromophobe renal cell carcinoma can metastasize to the head and neck region and should preferentially be treated with surgery and antiangiogenic therapy because of the associated morbidity and quality-of-life issues. PMID:24187640

  1. Cytogenetic characterization of three cell lines derived from primary cervical tumors of different histologic grade

    SciTech Connect

    Hann, E.; Beauregard, L.; Mikumo, R.

    1994-09-01

    Braum et al.(1993) established three cell lines from keratinizing and nonkeratinizing cervical carcinomas. These cell lines were subsequently analyzed for growth properties and the physical state of the human papillomavirus type 16 genome. TC140, derived from a keratinizing cervical tumor, contains human papillomavirus type 16 in the episomal state. TC-146A and TC-146B, derived from a nonkeratinizing large-cell cervical carcinoma, contain human papillomavirus type 16 in the integrated state. The goal of the present study was to cytogenetically characterize these cell lines, developed from cervical carcinoma with a defined histopathology, in order to shed additional light on the biological basis of the histological and clinical heterogeneity of cervical cancers. Information on solid tumors has been limited because they are often difficult to culture and the karyotypes on the available metaphases are often complex with unidentifiable markers. The chromosomes of these three cell lines were characterized in the present study using GTG-banding. For cell line 140, the most striking chromosomal abnormalities noted were the presence of an i(5p) or i(12p) marker, an isochromosome 8q marker and multiple copies of chromosome 9. For cell line 146A, the most notable chromosomal abnormalities noted were the presence of a marker chromosome 7 with additional materials present on the long arms, an isochomosome of the long arms of chromosome 8 and a question of chromosome 19 markers. For cell line 146B, the most notable chromosomal abnormalities were found to be a deleted X chromosome, a marker chromosome 7 with additional material on the long arm, an isochromosome 8q marker, and isochromosome 16q marker and one or more copies of an isochromosome 17q marker. Fluorescent in situ hybridization experiments performed using select probes further corroborate the results of the above-mentioned conventional cytogenetic studies.

  2. [Cervical cancer as a tracer condition: a proposal for evaluation of primary health care].

    PubMed

    Bottari, Clarissa Moraes de Sousa; Vasconcellos, Miguel Murat; Mendonça, Maria Helena Magalhães de

    2008-01-01

    The use of tracer conditions as an evaluative technique suggests the possibility of inferring the quality of health care and setting evaluation standards for programmed actions. As a government strategy, primary health care is a key element for reorganization of the Brazilian health care model. This study analyzes the use of cervical cancer as a tracer condition for assessing primary care. Based on the results from questions on measures to control the disease from the perspective of health professionals and cervical cancer patients, we constructed a matrix of indicators relating primary care attributes to process/results indicators. The analytical plan to validate the results used triangulation of methods, associating data from qualitative and quantitative approaches, in addition to combining and cross-analyzing the various actors' points of view. The results suggest that cervical cancer is an excellent tracer condition for primary care in general, based on the similarity of such concepts as accessibility, coverage, comprehensiveness, technical and scientific quality, and effectiveness.

  3. An unexpected reason for elevated human chorionic gonadotropin in a young woman Cervical squamous carcinoma

    PubMed Central

    Mustafa, Aynur; Bozdağ, Zehra; Tepe, Neslihan B.; Ozcan, Huseyin C.

    2016-01-01

    Human chorionic gonadotropin has been used for decades, in addition to specific investigations, to detect pregnancy, trophoblastic tumors, as well as congenital defects. Rarely, it can be elevated in non-trophoblastic tumors such as squamous cell cancers and germ cell tumors. A 33-year-old Asian Syrian female had irregular menses accompanied with feelings of heaviness in the vagina. In addition to routine investigations, we measured the serum beta human chorionic gonadotropin (ß-HCG) level (based on the patient’s complaint of amenorrhea), which was 50.05 ml UI/ml. Cervical biopsy revealed a non-keratinized large cell squamous carcinoma. After excluding other causes, ß-hCG elevation was explained by the ectopic secretion of cancer cells line. Cervical biopsy was suggestive of large cell non-keratinizing squamous cell carcinoma and positive for human chorionic gonadotropin on immunohistochemistry. As a result, we manage the possibility of ectopic secretion of ß-HCG from non- trophoblastic disease. PMID:27464870

  4. An unexpected reason for elevated human chorionic gonadotropin in a young woman. Cervical squamous carcinoma.

    PubMed

    Mustafa, Aynur; Bozdag, Zehra; Tepe, Neslihan B; Ozcan, Husiyen C

    2016-08-01

    Human chorionic gonadotropin has been used for decades, in addition to specific investigations, to detect pregnancy, trophoblastic tumors, as well as congenital defects. Rarely, it can be elevated in  non-trophoblastic tumors such as squamous cell cancers and germ cell tumors. A 33-year-old Asian Syrian female had irregular menses accompanied with feelings of heaviness in the vagina. In addition to routine investigations, we measured the serum beta human chorionic gonadotropin (ß-HCG) level (based on the patient's complaint of amenorrhea), which was 50.05 ml UI/ml. Cervical biopsy revealed a non-keratinized large cell squamous carcinoma. After excluding other causes, ß-hCG elevation was explained by the ectopic secretion of cancer cells line. Cervical biopsy was suggestive of large cell non-keratinizing squamous cell carcinoma and positive for human chorionic gonadotropin on immunohistochemistry. As a result, we manage the possibility of ectopic secretion of ß-HCG from non- trophoblastic disease. PMID:27464870

  5. [Interstitial collagenase, gelatinases A and B and their endogenous inhibitors in squamous cell cervical carcinomas].

    PubMed

    Ryzhakova, O S; Zavalishina, L É; Andreeva, Iu Iu; Solov'eva, N I

    2013-01-01

    Interstitial collagenase and gelatinases are matrix metalloproteinases (MMP), which play the key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of interstitial collagenase (MMP-1), gelatinases A and B (MMP-2 and MMP-9) and their endogenous tissue inhibitors TIMP-1 and TIMP-2 as invasive factors of squamous cell carcinomas (SCC) of human cervical cancer. The study was carried out using 24 specimens of SCC and 11 specimens of adjacent to tumor morphologically normal tissue. All carcinoma specimens expressed E7 HPV-16 gene. It was shown that the increase of MMP-1 and MMP-9 expression and low of TIMP-1 and TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. The change of MMP-2 expression is not so significant and it is less influenced to the destructive potential. Moreover, substantial expression of MMP-1, MMP-2 and MMP-9 was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of cervical tumor.

  6. SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines

    PubMed Central

    Popovic, Jelena; Schwirtlich, Marija; Rankovic, Branislava; Stevanovic, Milena

    2015-01-01

    Although there is much evidence showing functional relationship between Hedgehog pathway, in particular Sonic hedgehog, and SOX transcription factors during embryonic development, scarce data are available regarding their crosstalk in cancer cells. SOX18 protein plays an important role in promoting tumor angiogenesis and therefore emerged as a promising potential target in antiangiogenic tumor therapy. Recently it became evident that expression of SOX18 gene in tumors is not restricted to endothelium of accompanying blood and lymphatic vessels, but in tumor cells as well.In this paper we have identified human SOX18 gene as a novel target gene of Hedgehog signaling in cervical carcinoma cell lines. We have presented data showing that expression of SOX18 gene is regulated by GLI1 and GLI2 transcription factors, final effectors of Hedgehog signaling, and that modulation of Hedgehog signaling activity in considerably influence SOX18 expression. We consider important that Hedgehog pathway inhibitors reduced SOX18 expression, thus showing, for the first time, possibility for manipulationwith SOX18 gene expression. In addition, we analyzed the role of SOX18 in malignant potential of cervical carcinoma cell line, and showed that its overexpression has no influence on cells proliferation and viability, but substantially promotes migration and invasion of cells in vitro. Pro-migratory effect of SOX18 suggests its role in promoting malignant spreading, possibly in response to Hedgehog activation. PMID:26588701

  7. Microvascular Reconstruction of Free Jejunal Graft in Larynx-preserving Esophagectomy for Cervical Esophageal Carcinoma

    PubMed Central

    Natori, Yuhei; Komoto, Masakazu; Matsumura, Takashi; Horiguchi, Masatoshi; Yoshizawa, Hidekazu; Iwanuma, Yoshimi; Tsurumaru, Masahioko; Kajiyama, Yoshiaki; Mizuno, Hiroshi

    2016-01-01

    Background: Losing the ability to speak severely affects the quality of life, and patients who have undergone laryngectomy tend to become depressed, which may lead to social withdrawal. Recently, with advancements in chemoradiotherapy and with alternative perspectives on postoperative quality of life, larynx preservation has been pursued; however, the selection of candidates and the optimal reconstructive procedure remain controversial. In this study, we retrospectively reviewed our experience with free jejunal graft for larynx-preserving cervical esophagectomy (LPCE), focusing on microvascular reconstruction. Methods: Seven patients underwent LPCE for cervical esophageal carcinoma, and defects were reconstructed by free jejunal transfer subsequently. We collected preoperative and postoperative data of the patients and assessed the importance of the procedure. Results: We mostly used the transverse cervical artery as the recipient, and a longer operative time was required, particularly for the regrowth cases. The operative field for microvascular anastomosis was more limited and deeper than those in the laryngectomy cases. Two graft necrosis cases were confirmed at postoperative day 9 or 15, and vessels contralateral from the graft were chosen as recipients in both patients. Conclusions: Microvascular reconstruction for free jejunal graft in LPCE differed in several ways from the procedure combined with laryngectomy. Compression from the tracheal cartilage to the pedicle was suspected as the reason of the necrosis clinically and pathologically. Therefore, we should select recipient vessels from the ipsilateral side of the graft, and careful and extended monitoring of the flap should be considered to make this procedure successful. PMID:27257562

  8. Sonoporation of Cervical Carcinoma Cells Affected with E6-Oncoprotein for the Treatment of Uterine Cancer

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Lee, Kyle; Pichardo, Samuel; Zehbe, Ingeborg

    2010-03-01

    Cervical cancer has been identified as the third leading cause of average years of life lost per person dying of cancer. Since essentially all cervical cancers contain copies of human papillomavirus (HPV) DNA, we propose a treatment that targets HPV-infected cells using strategies that re-introduce normal functions into the infected cells while sparing healthy cells. We propose the use of focused ultrasound in combination with microbubbles as means to deliver antibodies against the E6 protein present only in HPV positive cells. We conducted in vitro studies with cell cultures of SiHa cervical carcinoma cells seeded into Opticell™ chambers. An in-house ultrasound excitation apparatus was used to control and explore the optimal acoustic parameters in order to maximize delivery. We first validated the possibility of delivering the EX-EGFP-M02 vector (Genecopoeia) into the cells; 1.2 μL of activated microbubbles (Definity®) and 50 μg of the vector were mixed in media and then injected into the Opticell™ chamber. We used 32 μs pulses at a central frequency of 930 KHz with a repetition frequency of 1.5 kHz and total exposure duration of 30 s; six pressure values were tested (0 to 1 MPa). Fluorescence imaging was used to determine the levels of intracellular proteins and assess delivery. The delivery of an anti-α-Tubulin antibody was next tested and confirmed that the delivery into HPV16 positive cells was successful.

  9. Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

    PubMed Central

    Landy, Rebecca; Sasieni, Peter D.

    2016-01-01

    While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population‐based case–control study to examine whether cervical screening leads to early diagnosis and down‐staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age‐matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non‐attenders. The overall OR comparing women up to date with screening with non‐attenders was 0.46 (95% CI: 0.39–0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15–0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46–1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52–3.62) compared to non‐attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05–0.13); however, the odds doubled 3–5 years after a negative test (OR: 2.30, 95% CI: 1.67–3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas. PMID:27096255

  10. Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo.

    PubMed

    Sekuła, Małgorzata; Miekus, Katarzyna; Majka, Marcin

    2014-06-01

    Cervical carcinoma is frequently diagnosed among women, particularly in low and middle income countries. In this study, we investigated the role of the SDF-1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in vivo. Downregulation of CXCR4 receptor using an RNA interference system led to almost complete inhibition of the receptor expression, activation and function. CXCR4 receptor silencing led to decreased ability to signal, to induce migration and to form holoclone-like colonies, with no influence on viability/proliferation of the cells. CXCR4-deficient cells had also significantly lower levels of MMP-9. Interestingly, downregulation of CXCR4 expression resulted in reduced tumor growth in vivo. Tumors generated by CXCR4-deficient cells had also lower expression of the proliferation marker Ki‑67 and decreased ability to engraft into lungs and spleen. Taken together, our results indicate that CXCR4 receptor may play an important role during cervical carcinoma invasion. In our study CXCR4 influenced invasive properties of cervical carcinoma cells both in vitro and in vivo.

  11. Expression of endothelin 1 and endothelin A receptor in HPV-associated cervical carcinoma: new potential targets for anticancer therapy.

    PubMed

    Venuti, A; Salani, D; Manni, V; Poggiali, F; Bagnato, A

    2000-11-01

    Human papillomaviruses (HPV) are associated with cervical cancer and interact with growth factors that may enhance malignant transformation of cervical carcinoma cells. Endothelin-1 (ET-1) is released from HPV transfected keratinocytes and induces increased growth response in these cell lines in comparison with normal cells. In the present study several cervical carcinoma cell lines have been analyzed to investigate the expression of ET-1 and its receptors as well as their involvement in tumor growth. All HPV-positive cancer cells secreted ET-1 and expressed mRNA for ET-1 and its receptors, whereas a HPV-negative carcinoma cell line expressed only the ETBR mRNA and didn't secrete ET-1. Binding studies showed that HPV-associated cells expressed an increased number of functional ETAR. ET-1 stimulated a marked dose-dependent increase in [3H]-thymidine incorporation with respect to the normal cells whereas ET-3 and ETBR agonists had no effect. In HPV-positive cancer cells, a specific antagonist of ETAR inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated cervical tumor cells, whereas the ETBR antagonist had no effect. These results demonstrate that ET-1 participates in the progression of neoplastic growth in HPV-associated carcinoma, in which ETAR are increased and could be targeted for antitumor therapy.

  12. IMP3 expression is associated with poor survival in cervical squamous cell carcinoma.

    PubMed

    Wei, Qingzhu; Yan, Jinhai; Fu, Bo; Liu, Jianghuan; Zhong, Ling; Yang, Qiao; Zhao, Tong

    2014-11-01

    Insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3) is an oncofetal protein that promotes tumor progression and metastasis in a number of malignancies. However, the clinical significance of IMP3 expression in squamous cell carcinoma (SCC) of the uterine cervix is unclear. In this study, the correlation between IMP3 expression and cervical cancer progression and prognosis was assessed by immunohistochemistry. IMP3 expression was observed in a large number of tissue specimens from patients with normal cervical tissues, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and SCC. IMP3 protein and mRNA expression was also determined in the SiHa and HeLa human cervical cancer cell lines. IMP3 expression was observed in 0 (0%) of 62 CIN I, 0 (0%) of 38 CIN II, and 9 (8.7%) of 104 CIN III specimens. Of the 96 SCC cases, IMP3 expression was detected in 54 cases (56.3%). Significant difference in IMP3 expression existed between all of the groups tested (P < .001). IMP3 protein and mRNA expressions in SiHa and HeLa cell lines were dramatically increased, as compared with normal tissue (P < .001). IMP3 expression was significantly related to age (P < .001), International Federation of Gynecology and Obstetrics stage (P < .001), and lymph node metastasis (P = .001). IMP3 expression was also shown to be an independent prognostic factor in SCC. In conclusion, these findings suggest that IMP3 expression may be a prognostic indicator of SCC.

  13. Cisplatin and Radiation Therapy With or Without Triapine in Treating Patients With Previously Untreated Stage IB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma

  14. pO{sub 2} Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

    SciTech Connect

    Ellingsen, Christine; Ovrebo, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

    2012-07-15

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO{sub 2}) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO{sub 2} fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO{sub 2} was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO{sub 2} fluctuations, the pO{sub 2} fluctuation frequency in these regions, and the relative amplitude of the pO{sub 2} fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO{sub 2} in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO{sub 2} and, thus, protect tumor tissue from cycling hypoxia.

  15. Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

    PubMed Central

    Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

    2016-01-01

    Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

  16. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  17. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-04-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  18. Mutations in CIZ1 cause adult-onset primary cervical dystonia

    PubMed Central

    Xiao, Jianfeng; Uitti, Ryan J.; Zhao, Yu; Vemula, Satya R.; Perlmutter, Joel S.; Wszolek, Zbigniew K.; Maraganore, Demetrius M.; Auburger, Georg; Leube, Barbara; Lehnhoff, Katja; LeDoux, Mark S.

    2012-01-01

    Objective Primary dystonia is usually of adult onset, can be familial, and frequently involves the cervical musculature. Our goal was to identify the causal mutation in a family with adult-onset, primary cervical dystonia. Methods Linkage and haplotype analyses were combined with solution-based whole-exome capture and massively parallel sequencing in a large Caucasian pedigree with adult-onset, primary cervical dystonia to identify a cosegregating mutation. High-throughput screening and Sanger sequencing were completed in 308 Caucasians with familial or sporadic adult-onset cervical dystonia and matching controls for sequence variants in this mutant gene. Results Exome sequencing led to the identification of an exonic splicing enhancer mutation in Exon 7 of CIZ1 (c.790A>G, p.S264G) which encodes CIZ1, Cip1-interacting zinc finger protein 1. CIZ1 is a p21Cip1/Waf1-interacting zinc finger protein expressed in brain and involved in DNA synthesis and cell-cycle control. Using a minigene assay, we showed that c.790A>G altered CIZ1 splicing patterns. The p.S264G mutation also altered the nuclear localization of CIZ1. Screening in subjects with adult-onset cervical dystonia identified two additional CIZ1 missense mutations (p.P47S and p.R672M). Interpretation Mutations in CIZ1 may cause adult-onset, primary cervical dystonia, possibly by precipitating neurodevelopmental abnormalities that manifest in adults and/or G1/S cell-cycle dysregulation in the mature central nervous system. PMID:22447717

  19. Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive cervical carcinoma.

    PubMed Central

    Bethwaite, P. B.; Koreth, J.; Herrington, C. S.; McGee, J. O.

    1995-01-01

    Allelotypic detection of loss of heterozygosity (LOH) has been used to identify putative tumour-suppressor genes. Loci on human chromosome 11q23 are frequently altered in malignant disease, and LOH has been reported at an anonymous D11S29 locus at 11q23 in a proportion of breast and ovarian cancers and malignant melanomas. Previous studies have reported a high frequency of LOH in cervical carcinoma mapping to 11q23. Using polymerase chain reaction techniques employing probes for a recently described polymorphic dinucleotide microsatellite within this locus, we have searched for LOH in 69 cases of invasive cervical carcinoma. Genomic material was microdissected from sections cut from archival paraffin-embedded material, using the patients' constitutional genotype as a control Sixty-two (90%) of the cases were informative, and LOH occurred in 25/62 (40%) of tumours. Loss of an arm or single chromosome 11 is a well-recognised event in cervical carcinoma, and by employing other microsatellite polymorphisms mapping to 11q13 and 11p11-p12 we excluded those cases with widespread allelic loss. By doing so, LOH at D11S29 was found in 16/53 (30%) of tumours. The findings suggest a putative tumour-suppressor gene on 11q involved in cervical carcinogenesis. Images Figure 1 Figure 2 PMID:7710949

  20. Primary small cell undifferentiated (neuroendocrine) carcinoma of the maxillary sinus.

    PubMed

    Yadav, Santosh Kumar; Shetty, Premalatha

    2014-01-01

    Primary small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an extremely rare and distinctive tumor with aggressive clinical behavior. Moreover, SNECs originating in the head and neck region have been reported to be highly aggressive and to have a poor prognosis. This report describes a patient with a maxillary sinus SNEC who was successfully treated with neoadjuvant chemotherapy and concurrent chemoradiotherapy. PMID:24639904

  1. Cloning of monomeric human papillomavirus type 16 DNA integrated within cell DNA from a cervical carcinoma

    SciTech Connect

    Matsukura, T.; Kanda, T.; Furuno, A.; Yoshikawa, H.; Kawana, T.; Yoshiike, K.

    1986-06-01

    The authors have molecularly cloned and characterized monomeric human papillomavirus type 16 DNA with flanking cell DNA sequences from a cervical carcinoma. Determination of nucleotide sequence around the junctions of human papillomavirus and cell DNAs revealed that at the site of integration within cell DNA the cloned viral DNA had a deletion between nucleotides 1284 and 4471 (numbering system from K. Seedorf, G. Kraemmer, M. Duerst, S. Suhai, and W.G. Roewkamp), which includes the greater part of E1 gene and the entire E2 gene. In the remaining part of the E1 gene, three guanines were found at the location where two guanines at nucleotides 1137 and 1138 have been recorded. This additional guanine shifted the reading frame and erased an interruption in the E1 gene. The data strongly suggest that, like other papillomaviruses, human papillomavirus type 16 has an uninterrupted E1 gene.

  2. Cervical Screening for Women with Learning Disability: Current Practice and Attitudes within Primary Care in Edinburgh

    ERIC Educational Resources Information Center

    Wood, Rachael; Douglas, Margaret

    2007-01-01

    This study aimed to evaluate current practice in, and to explore primary care professionals' views about, providing cervical screening to women with learning disability, in two areas of Edinburgh. A postal questionnaire was sent to all 24 GP practices in the project area: 20 responded. Seven respondents were invited to participate in follow up…

  3. Disturbance of Tumor Necrosis Factor Alpha-Mediated Beta Interferon Signaling in Cervical Carcinoma Cells

    PubMed Central

    Bachmann, Anastasia; Hanke, Brigitte; Zawatzky, Rainer; Soto, Ubaldo; van Riggelen, Jan; zur Hausen, Harald; Rösl, Frank

    2002-01-01

    In the present study we show that malignant human papillomavirus (HPV)-positive cells lost their ability to synthesize endogenous beta interferon (IFN-β) upon tumor necrosis factor alpha (TNF-α) treatment. IFN-β transcription, however, was reinducible in nonmalignant HPV-positive cells, which was confirmed in functional protection assays against encephalomyocarditis virus or vesicular stomatitis virus infections. Addition of neutralizing antibodies against IFN-β blocked the antiviral effect, excluding the possibility that other IFN types were involved. Conversely, both malignant and immortalized cells could be protected against viral cytolysis when either IFN-β, IFN-α, or IFN-γ was added exogenously. This indicates that only the cross talk between TNF-α and the IFN-β pathways, and not IFN-α/β and IFN-γ signaling in general, is perturbed in cervical carcinoma cells. Notably, full virus protection was restricted exclusively to nonmalignant cells, indicating that the antiviral effect correlates with the growth-inhibitory and virus-suppressive properties of TNF-α. The IFN-regulatory factors IRF-1 and p48 (ISGF3γ) emerged as key regulatory molecules in the differential IFN-β response, since their transcription was either absent or only inefficiently enhanced in tumorigenic cells upon treatment with TNF-α. Inducibility of both genes, however, became reestablished in cervical carcinoma cells, which were complemented to nontumorigenicity after somatic cell hybridization. Complementation was paralleled by the entire reconstitution of cytokine-mediated IFN-β expression and the ability of TNF-α to exert an antiviral state. In contrast, under conditions where tumor suppression was not accomplished upon somatic cell hybridization, neither expression of IRF-1, p48, and IFN-β nor antiviral activity could be restored. PMID:11739693

  4. Deletion and translocation of chromosome 11q13 sequences in cervical carcinoma cell lines

    SciTech Connect

    Jesudasan, R.A.; Srivatsan, E.S.; Rahman, R.A.; Chandrashekharappa, S.; Evans, G.A.

    1995-03-01

    Molecular genetic studies on HeLa cell-derived nontumorigenic and tumorigenic hybrids have previously localized the HeLa cell tumor-suppressor gene to the long arm of chromosome 11. Extensive molecular and cytogenetic studies on HeLa cells have shown chromosome band 11q13 to be rearranged in this cell line. To determine whether q13 rearrangement is a nonrandom event in cervical carcinomas, six different human papilloma virus (HPV)-positive (HeLa, SiHa, Caski, C4-I, Me180, and Ms751) and two different HPV-negative (C33A and HT3) cell lines were studied. Long-range restriction mapping using a number of q13-specific probes showed molecular arrangements within 75 kb of INT2 probe in three HPV-positive cell lines (HeLa, SiHa, and Caski) and in an HPV-negative cell line (HT3). FISH using an INT2 YAC identified a breakpoint within the sequences spanned by this YAC in two of the cell lines, HeLa and Caski. INT2 cosmid derived from this YAC showed deletion of cosmid sequences in two other cell lines, SiHa and C33A. These two cell lines, however, retained cosmid sequences of Cyclin D1, a probe localized 100 kb proximal to INT2. Deletions being the hallmark of a tumor-suppressor gene, we conclude that the 100-kb interval between the two cosmids might contain sequences of the cervical carcinoma tumor-suppressor gene. 28 refs., 9 figs.

  5. Deletion and translocation of chromosome 11q13 sequences in cervical carcinoma cell lines.

    PubMed

    Jesudasan, R A; Rahman, R A; Chandrashekharappa, S; Evans, G A; Srivatsan, E S

    1995-03-01

    Molecular genetic studies on HeLa cell-derived nontumorigenic and tumorigenic hybrids have previously localized the HeLa cell tumor-suppressor gene to the long arm of chromosome 11. Extensive molecular and cytogenetic studies on HeLa cells have shown chromosome band 11q13 to be rearranged in this cell line. To determine whether q13 rearrangement is a nonrandom event in cervical carcinomas, six different human papilloma virus (HPV)-positive (HeLa, SiHa, Caski, C4-I, Me180, and Ms751) and two different HPV-negative (C33A and HT3) cell lines were studied. Long-range restriction mapping using a number of q13-specific probes showed molecular rearrangements within 75 kb of INT2 probe in three HPV-positive cell lines (HeLa, SiHa, and Caski) and in an HPV-negative cell line (HT3). FISH using an INT2 YAC identified a breakpoint within the sequences spanned by this YAC in two of the cell lines, HeLa and Caski. INT2 cosmid derived from this YAC showed deletion of cosmid sequences in two other cell lines, SiHa and C33A. These two cell lines, however, retained cosmid sequences of Cyclin D1, a probe localized 100 kb proximal to INT2. Deletions being the hallmark of a tumor-suppressor gene, we conclude that the 100-kb interval between the two cosmids might contain sequences of the cervical carcinoma tumor-suppressor gene. PMID:7887426

  6. Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: A retrospective analysis

    SciTech Connect

    Saibishkumar, Elantholi P. . E-mail: drsaibish@rediffmail.com; Patel, Firuza D.; Ghoshal, Sushmita; Kumar, Vinay; Karunanidhi, Gunaseelan; Sharma, Suresh C.

    2005-11-01

    Purpose: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. Methods and Materials: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. Results: The median follow-up was 34 months. The gap between surgery and RT was 23-198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. Conclusions: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity.

  7. High Dose-Rate Intracavitary Brachytherapy for Cervical Carcinomas With Lower Vaginal Infiltration

    SciTech Connect

    Kazumoto, Tomoko Kato, Shingo; Tabushi, Katsuyoshi; Kutsutani-Nakamura, Yuzuru; Mizuno, Hideyuki; Takahashi, Michiko; Shiromizu, Kenji; Saito, Yoshihiro

    2007-11-15

    Purpose: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. Methods and Materials: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional ICBT was applied as 'pear-shaped' isodose curve. Then 3-4 more sessions per week of this new method of ICBT were performed. With a simple determination of the treatment volume, the cervix-parametrium, and the lower vagina were covered automatically and simultaneously by this program, that was designated as 'utero-vaginal brachytherapy'. The mean follow-up period was 87.4 months (range, 51.8-147.9 months). Results: Isodose curve for this program was 'galaxy-shaped'. Five-year local-progression-free survival and overall survival rates were 90.7% and 81.8%, respectively. Among those patients with late complications higher than Grade 2 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis. Conclusions: Because of the favorable treatment outcomes, this treatment-planning program with a simplified target-volume based dosimetry was proposed for cervical cancer with lower vaginal infiltration.

  8. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    SciTech Connect

    Ohara, Kiyoshi . E-mail: ki-ohara@md.tsukuba.ac.jp; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-03-15

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day{sup -1}) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day{sup -1} (median, 0.021 day{sup -1}) and late-assessed radioresponse from 0.009 to 0.091 day{sup -1} (median, 0.021 day{sup -1}), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R {sup 2} = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

  9. Cervical neck dissection without drains in well-differentiated thyroid carcinoma.

    PubMed

    Abboud, Bassam; Sleilaty, Ghassan; Tannoury, Jenny; Daher, Ronald; Abadjian, Gerard; Ghorra, Claude

    2011-12-01

    This study aims to review the safety of thyroidectomy combined with cervical neck dissection without drainage in well-differentiated thyroid carcinoma (WDTC). The medical records of consecutive patients who underwent thyroidectomy without drainage for WDTC were retrospectively reviewed. Group 1 included 123 patients who underwent thyroidectomy with central neck dissection and Group 2 included 46 patients who underwent thyroidectomy with central and lateral neck dissection. One hundred twenty-seven patients underwent thyroidectomy without neck dissection and were included in Group 3. Overall, 16 patients (5%) developed postoperative hematoma and/or seroma, seven patients (6%) in the Group 1, three patients (7%) in the Group 2, and six patients (5%) in Group 3. All patients had minor bleeding or seroma not requiring surgical intervention. Overall, 68 patients (23%) had transient postoperative hypocalcaemia, and four patients(1%) had permanent hypoparathyroidism. Seventeen patients (6%) had transient postoperative hoarseness and three had permanent vocal cord paralysis (0.6%). The postoperative stay for all groups was 1 day in 91 per cent of the cases. Patients from Groups 1 and 2 had no increased perioperative local complications or length of stay as compared with Group 3. Cervical neck dissection and thyroidectomy without drains is safe and effective in the treatment of WDTC.

  10. [The relationship between expression of basement membrane in squamous cell carcinoma of oral cavity and cervical lymph node metastasis].

    PubMed

    Gu, X; Shen, Z; Liu, S; Qian, Z

    1997-01-01

    Fifty seven cases of oral squamous cell carcinoma (SCC) were studied by immunohistochemical ABC method using type IV collagen and laminin antibody to investigate the relationship between expression and distribution of basement membrane in oral SCC and clinicopathologic characteristics and cervical lymph node metastasis. The distribution of basement membrane of oral SCC was discontinuous and in some cases the membranes disappeared. There was highly significant correlation between the staining patterns together with histologic differentiation degrees and cervical lymph node metastasis (P < 0.05). These indicate that the expression of baasement membrane in oral SCC may be a useful parameter for evaluation of tumor histologic differentiation and tumor invasion and metastasis. PMID:9868026

  11. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  12. Primary squamous cell carcinoma of the liver: a case report

    PubMed Central

    Yoo, Tae Kyung; Kim, Byung Ik; Han, Eun Na; Kim, Dong Hyung; Yoo, Jung Hee; Lee, Seung Jae; Cho, Yong Kyun; Kim, Hong Joo

    2016-01-01

    Primary squamous cell carcinoma (SCC) of the liver is very rare, and few cases have been reported in Korea. Primary SCC of the liver is known to be associated with hepatic cysts and intrahepatic stones. A 71-year-old male was admitted to our hospital, and a abdominal computed tomography scan revealed a 10 × 6 cm mass in the liver. Analysis of a biopsy sample suggested SCC, and so our team performed a thorough workup to find the primary lesion, which was revealed hepatoma as a pure primary SCC of the liver with multiple distant metastases. The patient was treated with one cycle of radiotherapy, transferred to another hospital for hospice care, and then died 1 month after discharge. PMID:27044770

  13. Secondary Primary Malignancy Risk in Patients With Cervical Cancer in Taiwan

    PubMed Central

    Teng, Chung-Jen; Huon, Leh-Kiong; Hu, Yu-Wen; Yeh, Chiu-Mei; Chao, Yee; Yang, Muh-Hwa; Chen, Tzeng-Ji; Hung, Yi-Ping; Liu, Chia-Jen

    2015-01-01

    Abstract To evaluate the risk of secondary primary malignancy (SPM) in patients with cervical cancer using a nationwide population-based dataset. Patients newly diagnosed with cervical cancer between 1997 and 2011 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated by comparing with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models. During the 14-year study period (follow-up of 223,062 person-years), 2004 cancers developed in 35,175 patients with cervical cancer. The SIR for all cancers was 1.56 (95% confidence interval, 1.50–1.63, P < 0.001). SIRs for follow-up periods of >10, 5 to 10, 1 to 5, and <1 year were 1.37, 1.51, 1.34, and 2.59, respectively. After the exclusion of SPM occurring within 1 year of cervical cancer diagnosis, SIRs were significantly higher for cancers of the esophagus (2.05), stomach (1.38), colon, rectum, and anus (1.36); lung and mediastinum (2.28), bone and soft tissue (2.23), uterus (3.76), bladder (2.26), and kidneys (1.41). Multivariate analysis showed that age ≥60 was a significant SPM risk factor (hazard ratio [HR] 1.59). Different treatments for cervical cancer, including radiotherapy (HR 1.41) and chemotherapy (HR 1.27), had different impacts on SPM risk. Carboplatin and fluorouracil independently increased SPM risk in cervical cancer patients. Patients with cervical cancer are at increased risk of SPM development. Age ≥60 years, chemotherapy, and radiotherapy are independent risk factors. Carboplatin and fluorouracil also increased SPM risk independently. Close surveillance of patients at high risk should be considered for the early detection of SPMs. PMID:26512575

  14. Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature

    PubMed Central

    Amorim, Gustavo Moreira; Quintella, Danielle; Cuzzi, Tullia; Rodrigues, Rosangela; Ramos-e-Silva, Marcia

    2015-01-01

    We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor) is discussed. PMID:26557073

  15. Primary intraosseous carcinoma of the mandible: A report of two cases

    PubMed Central

    Sengupta, Shamindra; Vij, Hitesh; Vij, Ruchieka

    2010-01-01

    Primary intraosseous carcinoma arising as a de novo lesion is a unique and rare carcinoma affecting the jaws, especially at younger ages. Two case reports, a 26-year-old Indian female with primary intraosseous squamous cell carcinoma and a 16-year-old Indian male with intraosseous carcinoma arising in an odontogenic cyst, both within the body of the mandible, are presented here. PMID:21731266

  16. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    SciTech Connect

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  17. Genomic alterations in cervical carcinoma: Losses of chromosome heterozygosity (LOH) correlated with cytogenetic, HPV, and p53 evaluations

    SciTech Connect

    Klinger, H.P.; Mullokandov, M.; Khollodilov, N.G.

    1994-09-01

    This study was undertaken to obtain indications of chromosomes likely to carry tumorigenicity suppressor genes the loss of function of which play a role in the origin or progression of cervical carcinomas. PCR and electrophoresis with primers for 73 highly polymorphic microsatellite chromosome markers were used to determine the incidence of LOH of all of the autosomes in 38 cervical carcinomas. According to these criteria 14 of the autosomes are involved in LOH in 24% to 42% of the tumors. This involves chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 16, 18 and 19. Most frequently involved are chromosomes 3 and 6 with LOH in 42% of the tumors. The chromosomes next most frequently involved are 4, 7, 11 and 18, with LOH in 31-32% of cases. Chromosomes 1, 2, 5, 8 and 16 each had LOH in 29% of the tumors; 9 and 13 each in 26%; and 19 in 24% of the tumors. All other autosomes had LOH in 18% or fewer of the tumors. Cytogenetic analyses performed on direct preparations from many of the same tumors agreed well with the molecular LOH assays. Correlation of the information obtained with both of these methods provides considerable insight into the mechanisms involved in the occurrence of these chromosome alterations. Chromosome 3 is the third most frequent chromosome involved in LOH in all types of cancer. In cervical carcinomas the region most frequently involved is 3p13-p25, which is a segment within which suppressors have been implicated in several other types of malignancies. Chromosome 6 on the other hand is rarely involved in other neoplasias and this appears to be unique to cervical carcinomas. Of interest was the finding that many of the HPV-negative tumors had LOH of chromosome 17 and many of these expressed mutant p53. The latter tumors occur in older women and are on the average much more aggressive than the HPV-positive tumors.

  18. SU-E-J-88: The Study of Setup Error Measured by CBCT in Postoperative Radiotherapy for Cervical Carcinoma

    SciTech Connect

    Runxiao, L; Aikun, W; Xiaomei, F; Jing, W

    2015-06-15

    Purpose: To compare two registration methods in the CBCT guided radiotherapy for cervical carcinoma, analyze the setup errors and registration methods, determine the margin required for clinical target volume(CTV) extending to planning target volume(PTV). Methods: Twenty patients with cervical carcinoma were enrolled. All patients were underwent CT simulation in the supine position. Transfering the CT images to the treatment planning system and defining the CTV, PTV and the organs at risk (OAR), then transmit them to the XVI workshop. CBCT scans were performed before radiotherapy and registered to planning CT images according to bone and gray value registration methods. Compared two methods and obtain left-right(X), superior-inferior(Y), anterior-posterior (Z) setup errors, the margin required for CTV to PTV were calculated. Results: Setup errors were unavoidable in postoperative cervical carcinoma irradiation. The setup errors measured by method of bone (systemic ± random) on X(1eft.right),Y(superior.inferior),Z(anterior.posterior) directions were(0.24±3.62),(0.77±5.05) and (0.13±3.89)mm, respectively, the setup errors measured by method of grey (systemic ± random) on X(1eft-right), Y(superior-inferior), Z(anterior-posterior) directions were(0.31±3.93), (0.85±5.16) and (0.21±4.12)mm, respectively.The spatial distributions of setup error was maximum in Y direction. The margins were 4 mm in X axis, 6 mm in Y axis, 4 mm in Z axis respectively.These two registration methods were similar and highly recommended. Conclusion: Both bone and grey registration methods could offer an accurate setup error. The influence of setup errors of a PTV margin would be suggested by 4mm, 4mm and 6mm on X, Y and Z directions for postoperative radiotherapy for cervical carcinoma.

  19. Primary retroperitoneal Merkel cell carcinoma: Case report and literature review

    PubMed Central

    Quiroz-Sandoval, Osvaldo A.; Cuellar-Hubbe, Mario; Lino-Silva, Leonardo S.; Salcedo-Hernández, Rosa A.; López-Basave, Horacio N.; Padilla-Rosciano, Alejandro E.; León-Takahashi, Alberto M.; Herrera-Gómez, Ángel

    2015-01-01

    Background Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that affects elderly patients and typically arises in sun-exposed skin. The disease is very rare and only few cases present with no apparent skin lesion. In the retroperitoneum there are only two cases reported in the literature. Case presentation We report a case of a 54-year-old Mexican male with MCC, which presented as a large retroperitoneal mass. Pathological and immunohistochemical analysis of the transabdominal CT-guided biopsy specimen revealed a MCC. The patient underwent preoperative chemotherapy followed by a laparotomy and the mass was successfully excised. Discussion There are two possible explanations for what occurred in our patient. The most plausible theory is the retroperitoneal mass could be a massively enlarged lymph node where precursor cells became neoplastic. This would be consistent with a presumptive diagnosis of primary nodal disease. Moreover, metastasis to the retroperitoneal lymph nodes has been reported as relatively common when compared to other sites such as liver, bone, brain and skin. The less probable theory is the non-described “regression” phenomena of a cutaneous MCC, but we are not found a primary skin lesion. Conclusion Preoperative chemotherapy and excision of the primary tumor is the surgical treatment of choice for retroperitoneal MCC. We propose that further studies are needed to elucidate the true efficacy of chemotherapy in conventional and unconventional patients with MCC. PMID:26708276

  20. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  1. Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

    PubMed

    Liu, De-Qing; Li, Fang-Fang; Zhang, Jiang-Bo; Zhou, Tie-Jun; Xue, Wen-Qiong; Zheng, Xiao-Hui; Chen, Yuan-Bin; Liao, Xiao-Yu; Zhang, Lan; Zhang, Shao-Dan; Hu, Ye-Zhu; Jia, Wei-Hua

    2015-07-07

    Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

  2. Girdin expression in cervical carcinoma and its role in the malignant properties of HeLa cells

    PubMed Central

    JIANG, PING; REN, YA-LI; LI, JIA-LIANG; LUO, JUN

    2016-01-01

    Cervical cancer is a major cause of mortality in females worldwide, with the majority of cases reported in developing countries. The molecular mechanisms of this disease are unclear. However, increasing evidence indicates that the expression or overexpression of Girdin is associated with a poor prognosis in a variety of cancer types. Therefore, the aim of the current study was to evaluate the potential association between Girdin expression, and malignant properties of cervical cancer lesions and HeLa cells. Girdin protein expression was examined in 87 samples of cervical squamous cell lesions, including intraepithelial neoplasia (grades I and III) and invasive carcinoma, using immunohistochemical (IHC) staining. A short-hairpin RNA (shRNA) approach was employed to specifically suppress the expression of Girdin mRNA in HeLa cells in vitro, allowing the role of Girdin in a number of malignant properties to be evaluated. Girdin protein was observed in the cytoplasm of 79/87 (90.8%) cervical cancer lesion specimens. However, no positive Girdin signals were identified in healthy cervical squamous epithelium samples. Furthermore, a significant correlation between Girdin expression and lesion grade was identified (Spearman's correlation coefficient, 0.566; P<0.001). When Girdin was suppressed by Girdin shRNA, the rate of HeLa cell growth was significantly reduced in vitro (P<0.05). Additional analysis determined that Girdin was associated with serum-deprived induced HeLa apoptosis. Thus, patients with high-grade cervical cancer tumors exhibited a strong expression for Girdin, and Girdin appears to key in HeLa cell proliferation and serum-deprived induced apoptosis, supporting the hypothesis that Girdin may be important in the process of cervical carcinogenesis. PMID:27073494

  3. Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation.

    PubMed

    Dumoff, Kimberly L; Chu, Christina S; Harris, Eleanor E; Holtz, David; Xu, Xiaowei; Zhang, Paul J; Acs, Geza

    2006-05-01

    Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r = 0.8962, P < 0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (P < 0.0001) and nodal metastasis (P = 0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P = 0.0009) and overall (P = 0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

  4. Primary salivary duct carcinoma arising from the Stensen duct.

    PubMed

    Noda, Kenji; Hirano, Takashi; Okamoto, Tomoyo; Suzuki, Masashi

    2016-09-01

    This report describes a salivary duct carcinoma (SDC) arising from the extraglandular portion of the Stensen duct. The patient was a 56-year-old man who presented with a palpable, elastic, hard mass without tenderness in the right cheek. Computed tomography revealed a tumor of the extraglandular portion of the Stensen duct. Supraomohyoid right neck dissection and total right parotidectomy were performed, and the histologic diagnosis was SDC of the Stensen duct. Postoperatively, the patient received no additional treatment. Neither recurrence nor metastasis was observed during 4 years of follow-up examination. SDC of the Stensen duct is extremely rare. To our knowledge, there is no report that describes primary SDC arising from that location. We also believe this is the first report that describes the clinical course of primary SDC arising from a Stensen duct. PMID:27657321

  5. Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ.

    PubMed

    Yamamoto, Junya; Ohshima, Koichi; Ikeda, Seiyou; Iwashita, Akinori; Kikuchi, Masahiro

    2003-11-01

    Esophageal small cell carcinoma (SmCC) is a rarer, more highly aggressive, and more rapidly growing neoplasm than esophageal squamous cell carcinoma (SqCC). SmCC and SqCC also differ in terms of chemotherapy of choice, response to therapy, and prognosis. Accordingly, it is important to differentiate the 2 carcinomas. We studied the histology and immunohistochemical profiles of 6 cases of esophageal SmCC to elucidate the correct diagnosis of this tumor. We performed immunohistochemical analysis antibodies against cytokeratins (CKAE1/AE3, CKCAM5.2, CK34betaE12, CK7, CK8, CK10/13, and CK19), epithelial membrane antigen (EMA), neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin-A, S-100 protein, carcinoembryonic antigen (CEA), E-cadherin, thyroid transcription factor-1 (TTF-1), and p53. In 3 of the 6 SmCCs, heterogeneous components of in situ or invasive SqCC were observed. SqCC was found in the mucosa adjacent to the main SmCC, and the boundary between SmCC and SqCC was distinct, with no transitional features. Staining for NCAM, NSE, and chromogranin-A was positive in SmCCs, but negative in SqCCs. Both SmCCs and SqCCs were positive for CKAE1/AE3, CKCAM5.2, CK8, and EMA, but only SqCCs were positive for CK34betaE12 and CK19. Moreover, SmCCs containing SqCC components were positive for CEA and E-cadherin, whereas SmCCs without SqCC were negative. Our study suggests that NCAM and NSE are useful markers in diagnosing esophageal SmCC, and CK34betaE12 and CK19 are useful for differentiating SqCC components from SmCC.

  6. Anatomic Invasive Depth Predicts Delayed Cervical Lymph Node Metastasis of Tongue Squamous Cell Carcinoma.

    PubMed

    Mitani, Sohei; Tomioka, Toshifumi; Hayashi, Ryuichi; Ugumori, Toru; Hato, Naohito; Fujii, Satoshi

    2016-07-01

    Delayed cervical lymph node metastasis (CLNM) is the most negative prognostic factor of tongue squamous cell carcinoma (SCC). This study analyzed the relationship between clinicopathologic factors, including anatomic invasive depth (AID), and CLNM. A total of 212 patients with clinically node-negative (cN0) tongue SCC who had undergone partial glossectomy through the mouth were eligible for this retrospective study. The deepest portions where tongue SCC cells invaded as determined by microscopic analyses were classified into 5 categories, including epithelial and submucosal tissue, lateral extrinsic tongue muscle (ETM), intrinsic tongue muscles (ITM), paralingual and sublingual spaces, and medial ETM according to AID. We examined the relationship between clinicopathologic factors including AID and delayed CLNM. Multivariate analysis demonstrated that AID was an independent predictive factor for delayed CLNM (P=0.0022; odds ratio=7.1). Deeper invasion than ITM, including ITM, paralingual and sublingual spaces, and medial ETM, had high sensitivity and negative predictive value for delayed CLNM (94.4% and 95.7%, respectively). Precise elucidation of AID may be useful for the preoperative decision for performing elective neck dissection. None of 11 patients in whom the deepest portion where tumor invaded to lateral ETM (according to AID) showed delayed CLNM, although tongue SCC T4a tumor is defined by the presence of invasion of cancer cells to ETM. Tumors with invasion to lateral ETM might have to be excluded from the pathologic T4a category. PMID:27186852

  7. Chlorogenic Acid Interaction with Cisplatin and Oxaliplatin: Studies in Cervical Carcinoma Cells.

    PubMed

    Catanzaro, Daniela; Filippini, Raffaella; Vianello, Caterina; Carrara, Maria; Ragazzi, Eugenio; Montopoli, Monica

    2016-04-01

    The antiproliferative effect of the naturally occurring polyphenol chlorogenic acid (CGA) was evaluated in combination with either cisplatin or oxaliplatin in human cervical carcinoma cell lines that were either sensitive (A431) or resistant to cisplatin (A431Pt), in order to provide evidence to overcome drug resistance. Cytotoxicity of platinating drugs (IC50 - 10(-6) - 10(-5) M) was enhanced by 1-2 orders of magnitude by increasing incubation times (1, 4, and 24 hours) in the two cell lines. CGA treatment presented low cytotoxicity per se (IC50 ~ 10(-4) M at 24 h) if compared with platinum drugs and its activity was similar in A431Pt cells and in their sensitive A431 counterpart. The combination of the platinating drugs with CGA (10(-6) - 10(-4) M) indicated variable effects on cytotoxicity, ranging from potentiation to various degrees of antagonism (in A431 cells) and no effect (in A431Pt cells). In order to explain the different cytotoxic activity elicited by oxaliplatin and cisplatin in association with CGA, the possible presence of chemical interactions was investigated by HPLC analysis. The drug association with CGA caused evident changes in their chromatographic profile, suggesting occurrence of in vitro chemical interactions.

  8. Screening of biomarkers in cervical squamous cell carcinomas via gene expression profiling.

    PubMed

    Chen, Bing; Li, Chundong; Zhang, Lei; Lv, Jiahui; Tong, Ying

    2015-11-01

    In the present study, gene expression profiles of high-grade squamous intraepithelial lesions (HSIL) and invasive cervical squamous cell carcinomas (CSCC) were analyzed using bioinformatic tools to identify key genes and potential biomarkers. Analyses of differentially expressed genes (DEGs) were performed for HSIL vs. normal control and invasive CSCC vs. normal control tissues using the Limma package in R. Pathway enrichment analysis was performed using KOBAS. A protein‑protein interaction (PPI) network for the DEGs in invasive CSCC was constructed using String. Functional enrichment analysis was performed for the DEGs in the PPI network using DAVID. Relevant small molecules were predicted using Cmap. A total of 633 and 881 DEGs were identified in HSIL and invasive CSCC, respectively, and the two groups had 305 DEGs in common. Genes associated with the mitogen-activated protein kinase signaling pathway were enriched in the HSIL, while cell cycle-associated genes were over‑represented in invasive CSCC. The PPI network, containing 72 upregulated genes and 434 edges, was illustrated. Functional enrichment analysis showed that the cell cycle was the most significant gene ontology term. A total of six small molecules associated with the pathology of CSCC were identified, including the anti-cancer drug piperlongumine, which showed a negative correlation. The findings of the present study not only enhanced the current understanding of the pathogenesis of CSCC, but may also be a basis for the development of novel therapies. PMID:26398134

  9. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines.

    PubMed

    Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique; Villa, Luisa Lina; Rahal, Paula

    2016-09-01

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. PMID:27240147

  10. Gonococcal phospholipase d modulates the expression and function of complement receptor 3 in primary cervical epithelial cells.

    PubMed

    Edwards, Jennifer L; Entz, David D; Apicella, Michael A

    2003-11-01

    CR3-mediated endocytosis is a primary mechanism by which Neisseria gonorrhoeae elicits membrane ruffling and cellular invasion of the cervical epithelia. Our data indicate that, upon infection of cervical epithelia, N. gonorrhoeae specifically releases proteins, including a phospholipase D (PLD) homolog, which facilitate membrane ruffling. To elucidate the function of gonococcal PLD in infection of the cervical epithelia, we constructed an N. gonorrhoeae PLD mutant. By comparative association and/or invasion assays, we demonstrated that PLD mutant gonococci are impaired in their ability to adhere to and to invade primary cervical cells. This defect can be rescued by the addition of supernatants obtained from wild-type-infected cell monolayers but not by exogenously added Streptomyces PLD. The decreased level of total cell association (i.e., adherence and invasion) observed for mutant gonococci is, in part, attributed to the inability of these bacteria to recruit CR3 to the cervical cell surface with extended infection. Using electron microscopy, we demonstrate that gonococcal PLD may be necessary to potentiate membrane ruffling and clustering of gonococci on the cervical cell surface. These data may be indicative of the inability of PLD mutant gonococci to recruit CR3 to the cervical cell surface. Alternatively, in the absence of gonococcal PLD, signal transduction events required for CR3 clustering may not be activated. Collectively, our data indicate that PLD augments CR3-mediated gonococcus invasion of and survival within cervical epithelia. PMID:14573659

  11. The use of telemedicine in primary care for women with cervical cytological abnormalities.

    PubMed

    Etherington, lan J; Watts, Anne D; Hughes, Elisabeth; Lester, Helen E

    2002-01-01

    Telemedicine can be used in two different ways in the context of the National Health Service Cervical Screening Programme. The first method allows primary health-care providers to offer direct online booking of clinic appointments according to predefined algorithms based on the woman's cytological abnormality. The second method is telecolposcopy, which is designed to be used by nurses in primary care. Preliminary data confirm that such a system can be used reliably to make diagnoses. The technology is easily adaptable for realtime teleconsultation.

  12. Combination of external beam radiotherapy and Californium (Cf)-252 neutron intracavity brachytherapy is more effective in control of cervical squamous cell carcinoma than that of cervical adenocarcinoma.

    PubMed

    Xiong, Yanli; Liu, Jia; Chen, Shu; Zhou, Qian; Xu, Wenjing; Tang, Chen; Chen, Yonghong; Yang, Mei; Lei, Xin

    2015-09-01

    The objective of this study was to compare the effect of combined external beam radiotherapy (EBRT) and Californium (Cf)-252 neutron intracavity brachytherapy (ICBT) on cervical squamous versus adenocarcinoma. A total of 106 patients with stage IB-IIIB cervical cancer were accrued between January 2005 and May 2011 and divided into squamous cell carcinoma (SCC) and adenocarcinoma (AC) as a pair with 53 patients in each group according to tumor size, stage, age, and hemoglobin level using matched-pair design. The whole pelvic EBRT was performed with 2 Gy/fraction, 4 fractions/week. The total dose was 48-54 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20-36 Gy). Cf-252 neutron ICBT was delivered with 11 and 12 Gy-eq/f with the total dose at point A of 44 and 48 Gy-eq for SCC and AC patients, respectively. The mean follow-up time was 43 months. The 5-year LC, OS, DFS, LAC rates, and mean survival time were 66.0, 56.6, 52.8.0, 17.0%, and 76.4 ± 6.2 months, respectively, for AC patients, whereas they were 81.1, 69.8, 67.9, 11.3%, and 93.3 ± 4.3 months, respectively, for SCC patients. Furthermore, the early treatment toxicity was mild in both groups, the late treatment complications were mainly radiation-induced proctitis and cystitis, and there were no grade 3 or higher complications. Although the combination of Cf-252 neutron ICBT and EBRT was effective in both histology types of cervical cancer, a more aggressive strategy is needed to control cervical AC.

  13. Cervical Lymph Node Metastases From Unknown Primary Cancer: A Single-Institution Experience With Intensity-Modulated Radiotherapy

    SciTech Connect

    Villeneuve, Hugo; Despres, Philippe; Fortin, Bernard; Filion, Edith; Donath, David; Soulieres, Denis; Guertin, Louis; Ayad, Tarek; Christopoulos, Apostolos; Nguyen-Tan, Phuc Felix

    2012-04-01

    Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

  14. Genetic Variation in CXCL12 and Risk of Cervical Carcinoma: a Population-Based Case-Control Study

    PubMed Central

    Maley, Stephen N.; Schwartz, Stephen M.; Johnson, Lisa G.; Malkki, Mari; Du, Qin; Daling, Janet R.; Li, Shuying Sue; Zhao, Lue Ping; Petersdorf, Effie W.; Madeleine, Margaret M.

    2009-01-01

    Summary CXCL12 provides a chemotactic signal directing leukocyte migration and regulates metastatic behavior of tumor cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 (single SNP alleles and haplotypes) is associated with the risk of cervical carcinoma. Cases (N=917) were women diagnosed with invasive squamous cell cervical carcinoma (SCC), adenocarcinoma or adenosquamous carcinoma or adenocarcinoma in situ (ACIS) of the cervix, while residents of western Washington State. Control participants (N=849) were identified from the source population by random digit telephone dialing and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR=0.74, 95% C.I. 0.56–0.98). Among the ten common haplotypes inferred from the 9 tagSNPs, one haplotype defined by minor alleles at 5’ flanking SNP rs17885289 and rs266085, and common alleles at the other 7 SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR=0.72, 95% C.I. 0.56–0.93; recessive model OR=0.35, 95% C.I. 0.12–0.97; and log additive model OR=0.72, 95% C.I. 0.57–0.90). A stepwise procedure identified rs17885289, rs266085, and 3’ UTR SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3’ UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk. PMID:19788587

  15. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

    PubMed Central

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor. PMID:24817962

  16. Association of primary care physician sex with cervical cancer and mammography screening

    PubMed Central

    Ince-Cushman, Daniel; Correa, José A.; Shuldiner, Jennifer; Segouin, Judith

    2013-01-01

    Objective To assess whether the sex of primary care physicians is associated with differing rates of cervical cancer and mammography screening in a contemporary multicultural context. Design Structured medical record review of a retrospectively defined cohort. Setting Academic urban primary care clinic in Montreal, Que. Participants Seven male physicians and 9 female physicians, and all female patients aged 14 to 69 years registered to one of the physicians (N = 1948). Main outcome measures Screening compliance rates as measured by the elapsed time between the last visit and cervical cancer screening for all women in the study. In addition, in women aged 50 to 69 years, elapsed time between the last visit and mammography screening. Results Crude rates of Papanicolaou tests for patients of female primary care physicians were higher than for patients of male primary care physicians in all patient age groups. The lowest rates of Pap testing were among the youngest and oldest patients. After adjustment for patient age, first language, and region of birth, as well as physician age, the odds ratio of having a Pap test was 2.24 (95% CI 1.18 to 4.28) for the patients of female physicians, relative to those of male physicians. The adjusted odds ratio for mammography screening was 1.25 (95% CI 0.97 to 1.61) for patients of female physicians. Conclusion Male primary care physician sex is associated with lower rates of cervical cancer screening in an urban multicultural context. The study did not detect a physician sex effect in the mammography cohort. PMID:23341674

  17. Allelic loss of 10q23.3, the PTEN gene locus in cervical carcinoma from Northern Indian population.

    PubMed

    Rizvi, M Moshahid Alam; Alam, M Shabbir; Mehdi, Syed Jafar; Ali, Asgar; Batra, Swaraj

    2012-04-01

    Cervical cancer is one of the most common malignant diseases affecting women worldwide. Studies on loss of heterozygosity have been made for PTEN gene specific microsatellite markers in malignancies like breast, ovary and lungs and the results have shown a significant association. However the role of this gene is not clearly understood in cervical cancer from Indian population. A total of 135 cervical carcinoma tissues samples were analyzed for loss of heterozygosity. DNA was isolated from the samples and their matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers (D10S198 & D10S192) and one marker (D10S541) in flanking region and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 31 out of 133(23%) informative cases showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 8% (D10S192) to 13% (D10S198). Loss of heterozygosity was more frequently detected in intragenic region (D10S198 & D10S192) than in flanking region, D10S541 (21% versus 9%). These data argue that PTEN is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.

  18. Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival.

    PubMed

    Obermair, A; Cheuk, R; Horwood, K; Neudorfer, M; Janda, M; Giannis, G; Nicklin, J L; Perrin, L C; Crandon, A J

    2003-01-01

    To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant. PMID:14675347

  19. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  20. Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas.

    PubMed

    Li, Junwei; Bonifati, Serena; Hristov, Georgi; Marttila, Tiina; Valmary-Degano, Séverine; Stanzel, Sven; Schnölzer, Martina; Mougin, Christiane; Aprahamian, Marc; Grekova, Svitlana P; Raykov, Zahari; Rommelaere, Jean; Marchini, Antonio

    2013-10-01

    The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas.

  1. Hepatitis B virus infection and primary hepatocellular carcinoma.

    PubMed Central

    Feitelson, M

    1992-01-01

    For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC. PMID:1323384

  2. BRCA1 mutations in primary breast and ovarian carcinomas

    SciTech Connect

    Futreal, P.A.; Cochran, C.; Bennett, L.M.; Haugen-Strano, A.; Terry, L.; Barrett, J.C.; Wiseman, R.; Liu, Q.; Shattuck-Eidens, D.; Harshman, K.

    1994-10-07

    Loss of heterozygosity data from familial tumors suggested that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

  3. Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Huei-Jean; Chao, Angel; Chang, Chee-Jen; Chang, Ting-Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

    2010-11-15

    Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration.

  4. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas.

    PubMed

    Cho, Eun Yoon; Park, Kyeongmee; Do, Ingu; Cho, Junhun; Kim, Jiyun; Lee, Jeeyun; Kim, Seonwoo; Kim, Kyoung-Mee; Sohn, Tae Sung; Kang, Won Ki; Kim, Sung

    2013-05-01

    Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be

  5. Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF-IMRT) in Cervical Carcinoma Treatment.

    PubMed

    Kunogi, Hiroaki; Yamaguchi, Nanae; Terao, Yasuhisa; Sasai, Keisuke

    2016-01-01

    Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction. PMID

  6. Multiplex Identification of Human Papillomavirus 16 DNA Integration Sites in Cervical Carcinomas

    PubMed Central

    Xu, Bo; Chotewutmontri, Sasithorn; Wolf, Stephan; Klos, Ursula; Schmitz, Martina; Dürst, Matthias; Schwarz, Elisabeth

    2013-01-01

    Cervical cancer is caused by high-risk human papillomaviruses (HPV), in more than half of the worldwide cases by HPV16. Viral DNA integration into the host genome is a frequent mutation in cervical carcinogenesis. Because integration occurs into different genomic locations, it creates unique viral-cellular DNA junctions in every single case. This singularity complicates the precise identification of HPV integration sites enormously. We report here the development of a novel multiplex strategy for sequence determination of HPV16 DNA integration sites. It includes DNA fragmentation and adapter tagging, PCR enrichment of the HPV16 early region, Illumina next-generation sequencing, data processing, and validation of candidate integration sites by junction-PCR. This strategy was performed with 51 cervical cancer samples (47 primary tumors and 4 cell lines). Altogether 75 HPV16 integration sites (3′-junctions) were identified and assigned to the individual samples. By comparing the DNA junctions with the presence of viral oncogene fusion transcripts, 44 tumors could be classified into four groups: Tumors with one transcriptionally active HPV16 integrate (n = 12), tumors with transcribed and silent DNA junctions (n = 8), tumors carrying episomal HPV16 DNA (n = 10), and tumors with one to six DNA junctions, but without fusion transcripts (n = 14). The 3′-breakpoints of integrated HPV16 DNA show a statistically significant (p<0.05) preferential distribution within the early region segment upstream of the major splice acceptor underscoring the importance of deregulated viral oncogene expression for carcinogenesis. Half of the mapped HPV16 integration sites target cellular genes pointing to a direct influence of HPV integration on host genes (insertional mutagenesis). In summary, the multiplex strategy for HPV16 integration site determination worked very efficiently. It will open new avenues for comprehensive mapping of HPV integration sites and for the

  7. Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

    PubMed

    Yang, S D; Yu, J S; Lee, T T; Ni, M H; Yang, C C; Ho, Y S; Tsen, T Z

    1995-10-01

    Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

  8. Role of CD24 Protein in Predicting Metastatic Potential of Uterine Cervical Squamous Cell Carcinoma in Patients Treated With Radiotherapy

    SciTech Connect

    Kwon, Ghee Young; Ha, Hongil; Ahn, Geunghwan; Park, Seon Young; Huh, Seung Jae; Park, Won

    2007-11-15

    Purpose: The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. The aim of this study was to evaluate the immunoreactivity of uterine cervical squamous cell carcinoma to CD24 and determine whether CD24 is associated with clinical and pathologic parameters, including prognosis. Methods and Materials: The expression of CD24 protein was immunohistochemically studied in 73 cases of uterine cervical squamous cell carcinoma. All patients were treated with definitive radiotherapy alone or with concurrent chemoradiotherapy. Two pathologists independently analyzed the immunostaining; they did not have knowledge of the patient outcomes and evaluated any changes according to the percentage of tumor cells stained as follows: negative, <5% reactive; and positive, >5% reactive. Results: Positive staining was found in 43 cases (58.9%). The immunoreactivity did not correlate with age, International Federation of Gynecology and Obstetrics stage, lymph node metastasis, or tumor size. For patients who were CD24 negative, the total failure and distant metastasis rates were decreased about 20% compared with the rates for patients who were CD24 positive. On univariate analysis, the 5-year distant metastasis-free survival rate of CD24-negative patients was significantly greater than that of the CD24-positive patients (84.7% vs. 66.7%, respectively, p = 0.0497). The International Federation of Gynecology and Obstetrics stage and CD24 expression were significantly associated with distant metastasis-free survival on multivariate analysis. Conclusions: CD24 expression was a significant independent prognostic factor for distant metastasis-free survival in patients with uterine cervical squamous cell carcinoma. In the future, prospective determination of CD24 expression might aid clinical practice in the selection of the appropriate therapy for individual patients.

  9. mTOR as a Molecular Target in HPV-Associated Oral and Cervical Squamous Carcinomas

    PubMed Central

    Molinolo, Alfredo A.; Marsh, Christina; Dinali, Mohamed El; Gangane, Nitin; Jennison, Kaitlin; Hewitt, Stephen; Patel, Vyomesh; Seiwert, Tanguy Y.; Gutkind, J. Silvio

    2012-01-01

    Purpose The incidence of head and neck squamous cell carcinomas (HNSCC) associated with papillomavirus (HPV) infection has increased over the past decades in the US. We aimed at examining the global impact of HPV-associated HNSCC, and whether the established key role of mTOR activation in HNSCC is also observed in HPV+ HNSCC lesions, thereby providing novel treatment options for HPV-associated HNSCC patients. Experimental Design An international HNSCC tissue microarray (TMA) was used to analyze the expression of p16INK4A, a surrogate for HPV infection, and Akt-mTOR pathway activation. Results were confirmed in a large collection of HPV− and HPV+ HNSCC cases and in a cervical cancer (CCSCC) TMA. Observations were validated in HNSCC and CCSCC-derived cell lines, which were xenografted into immunodeficient mice for tumorigenesis assays. Results Approximately 20% of all HNSCC lesions could be classified as HPV+, irrespective of their country of origin. mTOR pathway activation was observed in most HPV+ HNSCC and CCSCC lesions and cell lines. The pre-clinical efficacy of mTOR inhibition by rapamycin and RAD001 was explored in HPV+ HNSCC and CCSCC tumor xenografts. Both mTOR inhibitors effectively decreased mTOR activity in vivo, and caused a remarkable decrease in tumor burden. These results emphasize the emerging global impact of HPV-related HNSCCs, and indicate that the activation of the mTOR pathway is a widespread event in both HPV− and HPV-associated HNSCC and CCSCC lesions. Conclusions The emerging results may provide a rationale for the clinical evaluation of mTOR inhibitors as a molecular targeted approach for the treatment of HPV-associated malignancies. PMID:22409888

  10. Episomal HPV 16 DNA isolated from a cervical carcinoma presents a partial duplication of the early region.

    PubMed

    Di Luca, D; Caselli, E; Monini, P; Rotola, A; Savioli, A; Cassai, E

    1989-09-01

    An invasive cervical carcinoma was found to harbor an episomal variant of human papillomavirus (HPV) type 16 DNA, with a size of about 10.1 kb. A genomic library of the tumor was constructed in bacteriophage lambda and a recombinant phage clone was isolated by screening with HPV 16 probe. Analysis by restriction mapping and Southern hybridization showed that the isolate contained a 2.2 kb duplication of the early region, which included part of E6, all E7 and part of E1 open reading frames. Possible consequences of this duplication for oncogenesis are discussed. PMID:2554613

  11. Disseminating a cervical cancer screening program through primary physicians in Hong Kong: a qualitative study

    PubMed Central

    2014-01-01

    Background Organized screening programs are more effective and equitable than opportunistic screening, yet governments face challenges to implement evidence-based programs. The objective of this study was to identify reasons for low levels of adoption among primary care physicians of a government sponsored Cervical Screening Program (CSP). Methods We conducted in-depth interviews with a snowball sample of primary care private and public primary care physicians in Hong Kong. Rogers’ theory of diffusion of innovation was used to understand the factors that influenced the physicians’ practice decisions. Results Our study found that Hong Kong physicians made the decision to encourage cervical screening and to participate in the CSP based primarily upon their clinical and business practice needs rather than upon the scientific evidence. The low rates of adoption of the CSP can be attributed to the physicians’ perceptions that the program’s complexity and incompatibility exceeded its relative advantages. Furthermore, women’s knowledge, attitudes and practices, identified as barriers by physicians, were also barriers to physicians adopting the CSP. Conclusions In both private and public health care systems, screening programs that rely on physicians must align program incentives with the physicians’ motivators or pursue additional demand creation policies to achieve objectives. PMID:24568606

  12. Structure-function relationships in rat medullary and cervical dorsal horns. I. Trigeminal primary afferents.

    PubMed

    Jacquin, M F; Renehan, W E; Mooney, R D; Rhoades, R W

    1986-06-01

    Intracellular recording and horseradish peroxidase (HRP) labeling were used to examine structure-function relationships in the medullary dorsal horn (MDH) and rostral cervical dorsal horn. In Nembutal-anesthetized rats, 78 trigeminal (V) primary afferent fibers were physiologically characterized and injected with HRP. Axons were sufficiently well stained to reconstruct all of their collaterals in the MDH. Many also extended into the cervical dorsal horn. Except for four axons, which responded best to noxious stimuli, all responded at short (mean = 0.50 ms) latencies to V ganglion shocks and to innocuous stimulation. Forty-five of our recovered fibers were associated with facial vibrissae and responded in either a rapidly adapting, slowly adapting type I, slowly adapting type IIa, or slowly adapting type IIb fashion. The adequate stimuli consisted of either slow deflection, high-velocity deflection, or a noxious pinch of the vibrissa follicle. The collaterals of all of the above-described mystacial vibrissa primary afferents proceeded directly to their region of arborization in a plane perpendicular to the lateral border of the medulla to collectively form a largely continuous, circumscribed terminal column. This longitudinally oriented column of terminal and en passant boutons angled from lamina V rostrally to lamina III caudally. In the magnocellular laminae of the MDH, all mystacial vibrissa primary afferents gave rise to similarly shaped arbors, regardless of their functional classification. While morphological variability was observed both within and between individual axons, variance between functional classes was no greater than that within a class. Moreover, number of collaterals, number of boutons, or bouton size did not distinguish functional classes. Nonmystacial vibrissa afferent arbors, with more caudal peripheral fields, had their primary arbor focus in C1 and C2 dorsal horn. These arbors had relatively little rostrocaudal overlap with mystacial

  13. Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients

    PubMed Central

    Liu, De-Qing; Li, Fang-Fang; Zhang, Jiang-Bo; Zhou, Tie-Jun; Xue, Wen-Qiong; Zheng, Xiao-Hui; Chen, Yuan-Bin; Liao, Xiao-Yu; Zhang, Lan; Zhang, Shao-Dan; Hu, Ye-Zhu; Jia, Wei-Hua

    2015-01-01

    Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16INK4a. Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients. PMID:26148476

  14. Expression of E-, P- and N-Cadherin and Its Clinical Significance in Cervical Squamous Cell Carcinoma and Precancerous Lesions

    PubMed Central

    Li, Baohua; Shi, Haiyan; Wang, Fenfen; Hong, Die; Lv, Weiguo; Xie, Xing; Cheng, Xiaodong

    2016-01-01

    Aberrant expression of classical cadherins has been observed in tumor invasion and metastasis, but its involvement in cervical carcinogenesis and cancer progression is not clear. We investigated E-, P- and N-cadherin expression and its significance in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). This retrospective study enrolled 508 patients admitted to Women's Hospital, School of Medicine, Zhejiang University with cervical lesions between January 2006 and December 2010. Immunochemical staining was performed in 98 samples of normal cervical epithelium (NC), 283 of CIN, and 127 of early-stage SCC. The association of cadherin staining with clinical characteristics and survival of the patients was evaluated by univariate and multivariate analysis. We found gradients of decreasing E-cadherin expression and increasing P-cadherin expression from NC through CIN to SCC. Aberrant E-cadherin and P-cadherin expression were significantly associated with clinical parameters indicating poor prognosis and shorter patient survival. Interestingly, we found very low levels of positive N-cadherin expression in CIN and SCC tissues that were not related to CIN or cancer. Pearson chi-square tests showed that E-cadherin expression in SCC was inversely correlated with P-cadherin expression (E-P switch), and was not correlated with N-cadherin expression. More important, patients with tissues exhibiting an E-P switch in expression had highly aggressive phenotypes and poorer prognosis than those without E-P switch expression. Our findings suggest that E-cadherin and P-cadherin, but not N-cadherin staining, might be useful in diagnosing CIN and for predicting prognosis in patients with early-stage SCC. PMID:27223886

  15. Multiple Primary Malignancies in Patients With Hepatocellular Carcinoma

    PubMed Central

    Xu, Wei; Liao, Wenjun; Ge, Penglei; Ren, Jinjun; Xu, Haifeng; Yang, Huayu; Sang, Xinting; Lu, Xin; Mao, Yilei

    2016-01-01

    Abstract Multiple primary malignancies (MPMs) are defined as 2 or more malignancies without subordinate relationship detected in different organs of an individual patient. Reports addressing MPM patients with hepatocellular carcinoma (HCC) are rare. We perform a 26-year follow-up study to investigate characteristics and prognosis of MPM patients associated with HCC due to the scarcity of relative researches. We retrospectively analyzed records of 40 patients who were diagnosed with MPM including HCC at the Departments of Surgery at Peking Union Medical College Hospital during 1989 to 2010. Their clinical characteristics and postoperative survival were compared with those of 448 patients who had HCC only during the study period. Among the 40 MPM patients, 11 were diagnosed synchronously and 29 metachronously. The most common extra-hepatic malignancies were lung cancer (15%), colorectal (12.5%), and thyroid carcinoma (12.5%). MPM patients had a negative hepatitis B virus infection rate (P = 0.013) and lower median alfa-fetoprotein (AFP) level (P = 0.001). Post-operative 1-, 3-, and 5-year overall survival (OS) rates for MPM patients were 82.5%, 64.5%, and 38.6% respectively, and showed no significant difference with those of HCC-only patients (84.7%, 54.2%, and 38.3% P = 0.726). During follow-up, 24 MPM patients died, including 17 (70.8%) who died of HCC-related causes. In univariate analysis, synchronous diagnosis, higher gamma glutamyltransferase (GGT) and/or AFP levels, tumor >5 cm and vascular invasion were significantly associated with shorter OS, but only tumor size was an independent OS factor in Cox modeling analysis. HCC should be considered as a potential second primary for all cancer survivors. Most MPM patients died of HCC-related causes and showed no significant difference in OS compared with HCC-only patients. Tumor size of HCC, rather than MPMs itself, was the only independent OS predictor for the MPM patients. PMID:27124050

  16. [Laparoscopic Galvin-TeLinde hysterectomy for treatment of a microinvasive cervical carcinoma].

    PubMed

    Skret, A; Obrzut, B; Chruściel, A

    1999-01-01

    The original technique of laparoscopical Galvin-TeLinde-hysterectomy in patients with FIGO IA1 cervical cancer is presented. Differences between this technique and classical abdominal procedure are discussed. Based on the presented case the authors discuss the significance of laparoscopy in cervical cancer treatment. PMID:10408079

  17. Detection of adeno-associated virus type 2 genome in cervical carcinoma

    PubMed Central

    Zheng, B Y; Li, X D; Wiklund, F; Chowdhry, S; Ångstrom, T; Hallmans, G; Dillner, J; Wallin, K L

    2006-01-01

    Adeno-associated virus (AAV) can impair the replication of other viruses. Adeno-associated virus seroprevalences have been reported to be lower among women with cervical cancer. In-vitro, AAV can interfere with the production of human papillomavirus virions. Adeno-associated virus-2 DNA has also been detected in cervical cancer tissue, although not consistently. To evaluate the role of AAV infection in relation to invasive cervical cancer, we performed a nested case–control study within a retrospectively followed population-based cohort. A total of 104 women who developed invasive cervical cancer on average 5.6 years of follow-up (range: 0.5 months–26.2 years) and 104 matched control-women who did not develop cervical cancer during the same follow-up time were tested for AAV and human papillomavirus by polymerase chain reaction. At baseline, two (2%) case-women and three (3%) control-women were positive for AAV-2 DNA. At the time of cancer diagnosis, 12 (12%) case-women and 3 (3%) matched control-women were positive for AAV-2 DNA. Persisting AAV infection was not evident. In conclusion, AAV-2 DNA was present in a low proportion of cervical cancers and we found no evidence that the presence of AAV in cervical smears of healthy women would be associated with reduced risk of cervical cancer. PMID:16736006

  18. Primary infiltrating ductal carcinoma of the axillary breast with metastasis to the contralateral chest wall.

    PubMed

    Sun, Li-Min; Meng, Fan-Yun; Chang, Nai-Jen; Lu, Chiao-Yi; Lu, Tsung-Hsien; Liang, Ji-An; Chung, Li-Min

    2013-06-01

    Primary infiltrating ductal carcinoma of the axillary breast is rare and has a high frequency of lymph node (LN) involvement. We report a woman with primary infiltrating ductal carcinoma arising from the right axillary breast with metastasis to the contralateral chest wall. Excisional biopsy of the left chest wall nodule and the right axillary mass was carried out and both showed invasive ductal carcinomas histologically. The lesion of the right axillary mass arose from the breast tissue, rather than the LN. Further surgery proved the right axillary LN metastasis. After further review, a primary infiltrating ductal carcinoma of the right axillary breast with metastasis to axillary LNs and contralateral chest wall was diagnosed. The patient also received chemotherapy and radiation and there was no evidence of tumor recurrence after treatment. The present report demonstrated a rare case with uncommon manifestation. Lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma. PMID:23602213

  19. Role of Radiotherapy in the Treatment of Cervical Lymph Node Metastases From an Unknown Primary Site: Retrospective Analysis of 113 Patients

    SciTech Connect

    Beldi, Debora; Jereczek-Fossa, Barbara A.; D'Onofrio, Alberto; Gambaro, Giuseppina; Fiore, Maria Rosaria; Pia, Francesco; Chiesa, Fausto; Orecchia, Roberto; Krengli, Marco

    2007-11-15

    Purpose: The management of patients with cervical lymph-node metastases from unknown primary site (UPS) remains a matter of discussion. This study aimed to analyze the results and prognostic factors in a series of patients treated with radiotherapy. Methods and Materials: Data from 113 patients who presented with cervical lymph nodes metastases from UPS treated from 1980 to 2004 were reviewed. Eighty-seven patients (77.0%) were squamous cell carcinoma (SCC). Ninety-one patients were treated with curative and 22 with palliative intent. Fifty-nine of 113 patients (52.2%) received surgery followed by radiotherapy and 54 of 113 (47.8%) received radiotherapy alone. Radiotherapy was delivered to the neck and pharyngeal mucosa in 67 patients and to the ipsilateral or bilateral neck in 45 patients. Twenty-one patients (18.5%) also received chemotherapy. Results: The 5-year overall survival rates were 40.7% for the entire group and 46.6% for the SCC subgroup. The occurrence of the occult primary was observed in 23 of 113 patients (20.3%), 19 (82.6%) within the head and neck region. At multivariate analysis, treatment with curative intent and extensive irradiation of bilateral neck and pharyngeal mucosa were favorable prognostic factors for the whole series, and treatment with curative intent, extensive irradiation of bilateral neck and pharyngeal mucosa, and absence of extracapsular spread were favorable prognostic factors for the SCC subgroup. Conclusions: Patients with cervical lymph node metastases from UPS have a similar prognosis to those affected by other head and neck malignancies. Curative treatment strategies including neck dissection and extensive irradiation by three-dimensional conformal radiation therapy resulted in significantly better outcomes.

  20. Primary hyperparathyroidism secondary to simultaneous bilateral parathyroid carcinoma.

    PubMed

    Brown, Jimmy J; Mohamed, Hezla; Williams-Smith, Lorraine; Osborne, Ryan; Coker, Joan; Yee, Brian

    2002-06-01

    Parathyroid carcinoma is a rare malignancy, and experience with its management is limited. It is generally accepted that surgery is the treatment of choice, and the initial operative intervention might represent the only chance for long-term success. At the time of surgery, a high index of suspicion for carcinoma is vital to performing the appropriate surgical procedures, because frozen-section diagnosis of parathyroid carcinoma is notoriously unreliable. In this article, we describe our experience with this rare entity.

  1. Type-specific human papillomavirus distribution in invasive cervical carcinomas in Paraguay. A study of 432 cases.

    PubMed

    Kasamatsu, Elena; Cubilla, Antonio L; Alemany, Laia; Chaux, Alcides; Tous, Sara; Mendoza, Laura; Paez, Malvina; Klaustermeier, Jo Ellen; Quint, Wim; Lloveras, Belen; de Sanjose, Silvia; Muñoz, Nubia; Bosch, Francisco Xavier

    2012-10-01

    Cervical carcinoma is the most common malignant tumor among woman in Paraguay. Cytological screening programs have not been successful and a plan for human papillomavirus (HPV) based-screening program and/or vaccination is under evaluation. This study aimed to identify the contribution of HPV genotypes in invasive cervical cancer in Paraguay to provide essential background data to guide and assess the introduction and impact of new preventive strategies based on HPV. Four hundred thirty two histologically confirmed cases (1960-2004) were analyzed. HPV detection in paraffin blocks was performed at the Catalan Institute of Oncology using PCR with SPF-10 broad spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe analysis. The majority of cases were squamous cell carcinoma (92.8%). Mean patients age was 48 years old. HPV DNA was detected in 73.1% of the cases and single infections were predominant (97.8%). The most common HPV single types were 16, 18, 45, 33, 31, 52, 35, and 39. 73.1% of HPV positive cases had an HPV 16, 18 as single infection. HPV16 was frequent in SCC whereas HPV 18 and 45 were prevalent in glandular tumors. Significant decrease of HPV 16 with age groups (P-trend = 0.022) and increase in other HPV types (P-trend > 0.001) were observed. The potential impact of HPV 16 and 18 for a vaccination program was 73.1%. The study provide a profile of the HPV situation in the country, with robust clinical, pathological and virological data which would permit a better cervical cancer screening and vaccination programs.

  2. Primary large-cell neuroendocrine carcinoma of the scrotum.

    PubMed

    Maricić, Anton; Katunarić, Miljenko; Sutalo, Nikica; Tomic, Snjezana; Jurisic, Davor; Petkovic, Marija; Zamolo, Gordana

    2010-06-01

    Neuroendocrine tumors (NETs) mostly develop from the neural crest cells but a few arise from neuroectoderm. They are common in the lungs and gastrointestinal tract but rare in the genitourinary tract. A 78-year-old man with no family history of malignant or hereditary diseases presented with a 3-month history of a rapidly growing asymptomatic scrotal nodule and swelling in the groin. He had a negative history of sexually transmitted disease and of trauma, fungal infection or chronic irritation in the scrotal area; there was no history of radiotherapy or exposure to chemicals or arsenic. Both the scrotal and groin lesions were excised with a minimum of 1.2 cm of normal skin. Examination of the specimen revealed a confined poorly differentiated large-cell neuroendocrine carcinoma with a metastasis to the inguinal lymph nodes. Three months after the excision we found a local recurrence. The recurrent tumor revealed tumor tissue concurrent with the primary lesion. To the best of our knowledge, there have been no previously published case reports on neuroendocrine tumor of the scrotum.

  3. Alcohol as a primary risk factor in oral squamous carcinoma.

    PubMed

    Mashberg, A; Garfinkel, L; Harris, S

    1981-01-01

    This case-control study investigates the role of alcohol as a primary risk factor in the development of oral cancer. A total of 181 patients diagnosed as having squamous carcinoma of the oral cavity were interviewed, and 497 controls. The relative risk for drinkers adjusted for smoking was 3.3, 15.2, and 10.6 for those who drank less than six, six to nine, and 10 or more whiskey equivalents (WEs) a day, respectively. The relative risk for smokers adjusted for drinking rose only from 3.2 to 4.5 to 5.0 for smokers of 10 to 19, 20 to 39, and 40 or more cigarettes a day, respectively. Beer/wine drinkers had much higher relative risks than the whiskey drinkers. The adjusted relative risk for whiskey drinkers consuming 10 or more WEs a day was 7.3; the adjusted relative risk for beer/wine drinkers consuming 10 or more WEs a day was 20.4. These results indicate that drinkers of six or more WEs a day may be at greater risk than smokers of 40 or more cigarettes a day, and that beer and wine may be greater risk factors than whiskey in the development of oral cancer.

  4. Intensity Modulated Proton Beam Radiation for Brachytherapy in Patients With Cervical Carcinoma

    SciTech Connect

    Clivio, Alessandro; Kluge, Anne; Cozzi, Luca; Köhler, Christhardt; Neumann, Oliver; Vanetti, Eugenio; Wlodarczyk, Waldemar; Marnitz, Simone

    2013-12-01

    Purpose: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose–volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. Methods and Materials: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). Results: The dose to the high-risk volume was calculated with α/β = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D{sub 98%} was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/β = 3) to 2 cm{sup 3} of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. Conclusion: In patients who are not eligible for brachytherapy, IMPT as a boost

  5. [Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (review of the own data)].

    PubMed

    Solovуeva, N I; Timoshenko, O S; Gureeva, T A; Kugaevskaya, E V

    2015-01-01

    Expression of matrix metalloproteinases (MMPs) and their endogenous regulators has been investigated in squamous cervical carcinoma (SCC). The study included (i) immortalized fibroblasts (IF) and three clones of fibroblasts transformed by oncogene E7 HPV-16 (TF); (ii) cell lines associated with HPV-16 and HPV-18; (iii) tumor tissue samples from patients with SCC, associated with gene E7 HPV-16. Transfection of fibroblasts with the E7 HPV16 oncogen was accompanied by induction of collagenase (MMP-1, MMP-14) and gelatinase (MMP-9) gene expression and the increase in catalytic activity of these MMP, while gelatinase MMP-2 expression remained unchanged. Expression of MMP-9 was found only inTF. MMP-9 may serve as a TF marker. In TF expression mRNA TIMP-1 was decreased. The level of free endogenous inhibitors in TF was significantly lower then the level in IF. Expression MMP correlated with the tumorigenic potential of TF. Invasive potential of cell lines associated with HPV18 (HeLa and S4-1) was more pronounced than that of cell lines associated with HPV16 (SiHa and Caski). The cell lines differed substantially in the level of expression of MMPI and their endogenous regulators. In most cell lines mRNA levels of collagenases MMP-1 and MMP-14 and the activator (uPA) increased, while gelatinase MMP-2 mRNA and tissue inhibitors mRNAs changed insignificantly. MMP-9 expression in cell lines was not detected. Results of studies on these cell lines suggest existence of an imbalance in the system enzyme/inhibitor/activator, that increases destructive potential of these cells. The study of expression of MMP and their endogenous regulators performed using SCC tumor samples associated with HPV16 has shown that the invasive and metastatic potentials of tumor tissue in SCC is obviously determined by the increase of expression of collagenases MMP-1, MT1-MMP and gelatinase MMP-9, decreased expression of inhibitors (TIMP-1 and TIMP-2), and to a lesser extent to increased expression of

  6. WNT2 Promotes Cervical Carcinoma Metastasis and Induction of Epithelial-Mesenchymal Transition

    PubMed Central

    Xu, Jing; Zhang, Lan; Wang, Jianhua; Huang, Long; Huang, Shuting; Yuan, Linjing; Jia, Weihua; Yu, Xingjuan; Luo, Rongzhen; Zheng, Min

    2016-01-01

    Background Previously, we found an 11-gene signature could predict pelvic lymph node metastasis (PLNM), and WNT2 is one of the key genes in the signature. This study explored the expression and underlying mechanism of WNT2 in PLNM of cervical cancer. Methods WNT2 expression level in cervical cancer was detected using western blotting, quantitative PCR, and immunohistochemistry. Two WNT2-specific small interfering RNAs (siRNAs) were used to explore the effects of WNT2 on invasive and metastatic ability of cancer cells, and to reveal the possible mechanism of WNT2 affecting epithelial—mesenchymal transition (EMT). The correlation between WNT2 expression and PLNM was further investigated in clinical cervical specimens. Results Both WNT2 mRNA and protein expression was upregulated in cervical cancer. High WNT2 expression was significantly associated with tumor size, lymphovascular space involvement, positive parametrium, and most importantly, PLNM. PLNM and WNT2 expression were independent prognostic factors for overall survival and disease-free survival. WNT2 knockdown inhibited SiHa cell motility and invasion and reversed EMT by inhibiting the WNT2/β-catenin pathway. WNT2 overexpression in cervical cancer was associated with β-catenin activation and induction of EMT, which further contributed to metastasis in cervical cancer. Conclusion WNT2 might be a novel predictor of PLNM and a promising prognostic indicator in cervical cancer. PMID:27513465

  7. Papillomavirus, p53 alteration, and primary carcinoma of the vulva.

    PubMed

    Pilotti, S; D'Amato, L; Della Torre, G; Donghi, R; Longoni, A; Giarola, M; Sampietro, G; De Palo, G; Pierotti, M A; Rilke, F

    1995-12-01

    Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.

  8. Poorer Prognosis of Primary Signet-Ring Cell Carcinoma of the Breast Compared with Mucinous Carcinoma

    PubMed Central

    Lin, Qingzhong; Chen, Gang; Lu, Jianping; Zeng, Yi; Hu, Dan; Huang, Kai; Lin, Zhiwu; Yan, Jun

    2016-01-01

    Primary signet-ring cell carcinoma (PSRCC) of the breast is a rare entity and classified under mucin producing tumors in the WHO classification. However, little is known about the clinicopathological characteristics and clinical outcomes of PSRCC as opposed to mucinous carcinoma. Eleven patients with PSRCC in our center from 1995 to 2010 were evaluated in this study, as compared to 50 cases of mucinous breast cancer (MBC) during the same period. The clinicopathologic features of PSRCC compared to MBC were assessed. Furthermore, overall survival (OS) and disease-free survival (DFS) were calculated at 5 years of follow up. Patients with PSRCC showed more frequent lymphatic metastasis, higher Ki67 labeling index and more advanced stage disease than that of MBC (P = 0.018, p = 0.023, P = 0.000, respectively), although there was no difference in age, tumor size, and ER, PR expression between PSRCC and MBC. In addition, PSRCC was associated with simultaneous vimentin upregulation and E-cadherin downregulation. The 5-year OS of PSRCC (54.5%) was significantly lower than that of MBC (88%) (P = 0.004). Similarly, the DFS of PSRCC was poorer than that of MBC significantly (5-year DFS: 27.3% vs. 80%, P = 0.000). Conclusions Our results confirmed the more aggressive behavior of PSRCC compared to MBC. This tumor is frequently associated with more frequent lymphatic metastasis, higher Ki67 labeling index, more advanced stage disease as well as simultaneous vimentin upregulation and E-cadherin downregulation. Different management guidelines should be considered for the two types. PMID:27583684

  9. Prolonged remission of recurrent cervical carcinoma following paclitaxel and carboplatin chemotherapy with paclitaxel maintenance chemotherapy.

    PubMed

    Micha, John P; Sassoon, Aaron F; Wong, Humberto; Goldstein, Bram H

    2015-08-01

    Cervical cancer recurs in ~30% of cases, for which a favorable prognosis is often unattainable. We describe a cervical cancer patient who developed metastatic disease ~5 years after her initial diagnosis. She was subsequently treated with six cycles of paclitaxel (175 mg/m) and carboplatin area under the curve (AUC) 5 chemotherapy every 21 days, and paclitaxel (135 mg/m) maintenance therapy every 21 days; the patient has remained in clinical remission after more than 5 years of follow-up. Chemotherapy has not historically been effective in managing recurrent, persistent, or metastatic cervical cancer. However, our case study involving paclitaxel and carboplatin chemotherapy with maintenance chemotherapy represents one of the longest documented remission rates in association with the management of recurrent cervical cancer.

  10. Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells

    PubMed Central

    Jennings, Michael P.; Jen, Freda E.-C.; Roddam, Louise F.; Apicella, Michael A.; Edwards, Jennifer L.

    2013-01-01

    Summary Expression of type IV pili by Neisseria gonorrhoeae plays a critical role in mediating adherence to human epithelial cells. Gonococcal pilin is modified with an O-linked glycan, which may be present as a di- or monosaccharide because of phase variation of select pilin glycosylation genes. It is accepted that bacterial proteins may be glycosylated; less clear is how the protein glycan may mediate virulence. Using primary, human, cervical epithelial (i.e. pex) cells, we now provide evidence to indicate that the pilin glycan mediates productive cervical infection. In this regard, pilin glycan-deficient mutant gonococci exhibited an early hyper-adhesive phenotype but were attenuated in their ability to invade pex cells. Our data further indicate that the pilin glycan was required for gonococci to bind to the I-domain region of complement receptor 3, which is naturally expressed by pex cells. Comparative, quantitative, infection assays revealed that mutant gonococci lacking the pilin glycan did not bind to the I-domain when it is in a closed, low-affinity conformation and cannot induce an active conformation to complement receptor 3 during pex cell challenge. To our knowledge, these are the first data to directly demonstrate how a protein-associated bacterial glycan may contribute to pathogenesis. PMID:21371235

  11. Prophylactic human papillomavirus vaccination and primary prevention of cervical cancer: issues and challenges.

    PubMed

    Poljak, M

    2012-10-01

    Two prophylactic human papillomavirus (HPV) vaccines have been recently approved: one quadrivalent and the other a bivalent vaccine. When administered in a three-dose course to HPV-naive individuals, both vaccines exhibited excellent safety profiles and were highly efficacious against targeted clinical endpoints in large-scale international phase III clinical trials. Where coverage has been high for the appropriate target population, a reduction of HPV-related diseases with the shortest incubation periods has already been seen. By March 2012, universal HPV vaccination had been introduced into national vaccination programmes in more than 40 countries, but only in a few low-income and middle-income countries. With the growing market for HPV vaccines and competition between manufacturers, negotiated prices are already beginning to decline although they still remain out of reach of many countries. The great majority of countries are struggling to reach a level of coverage that will have the most impact on cervical cancer rates. Increasing coverage and improving completion of the HPV vaccine schedule, particularly of sexually naive females, is now the most important public-health issue in HPV vaccine efforts. A clear strategy for integrating primary (HPV vaccination) and secondary (screening) cervical cancer prevention must be agreed as soon as possible. Several second-generation prophylactic vaccines are being developed with the aim of resolving some of the limitations of the two current HPV prophylactic vaccines. PMID:22862799

  12. Overexpression of Phosphorylated 4E-BP1 Predicts for Tumor Recurrence and Reduced Survival in Cervical Carcinoma Treated With Postoperative Radiotherapy

    SciTech Connect

    Benavente, Sergio; Verges, Ramona; Hermosilla, Eduardo; Fumanal, Victor; Casanova, Nathalie; Garcia, Angel; Ramon y Cajal, Santiago; Giralt, Jordi

    2009-12-01

    Purpose: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. Methods and Materials: Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. Results: Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. Conclusion: In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.

  13. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells

    SciTech Connect

    Yao, Qing; Xu, Hui; Zhang, Qian-Qian; Zhou, Hui; Qu, Liang-Hu

    2009-10-23

    MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3'UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggest that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.

  14. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older.

    PubMed

    Meijer, Chris J L M; Berkhof, Johannes; Castle, Philip E; Hesselink, Albertus T; Franco, Eduardo L; Ronco, Guglielmo; Arbyn, Marc; Bosch, F Xavier; Cuzick, Jack; Dillner, Joakim; Heideman, Daniëlle A M; Snijders, Peter J F

    2009-02-01

    Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays.

  15. Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

    PubMed Central

    Chen, Hong; Wang, Jingjing; Yang, Hong; Chen, Dan; Li, Panpan

    2016-01-01

    Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer.

  16. Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

    PubMed Central

    Chen, Hong; Wang, Jingjing; Yang, Hong; Chen, Dan; Li, Panpan

    2016-01-01

    Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer. PMID:27698840

  17. Primary candidiasis and squamous cell carcinoma of the larynx: report of a case.

    PubMed

    Lee, Dong Hoon; Cho, Hyong Ho

    2013-02-01

    Primary candidiasis is rare and often confused with a pre-cancerous lesion, squamous cell carcinoma, or verrucous carcinoma. We report an extremely rare case of squamous cell carcinoma of the vocal cord following primary candidiasis. A 62-year-old man presented to our department reporting a 1-month history of hoarseness. He underwent laryngeal microscopic surgery for a presumptive diagnosis of glottic carcinoma. Histopathologic examination revealed candidiasis and scattered moderate dysplasia. He was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis. However, the 42-month follow-up examination revealed a focal whitish lesion on the right true vocal cord, and a repeat biopsy of this area revealed squamous cell carcinoma without evidence of candidiasis. The patient was treated with radiotherapy and remains well with no signs of tumor recurrence or candidiasis.

  18. Biomarkers in Cervical Cancer

    PubMed Central

    Yim, Eun-Kyoung; Park, Jong-Sup

    2006-01-01

    Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervical cancer incidence and reduced deaths, but cervical cancer still remains a global health burden. The biomarker discovery for accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology. PMID:19690652

  19. Giant cystic primary mucoepidermoid carcinoma of mandible: a rare case and literature review.

    PubMed

    Verma, Roshan Kumar; Sunku, Satheesh Kumar; Bal, Amanjeet; Panda, Naresh K

    2014-01-01

    Primary intra-osseous mucoepidermoid carcinoma arising from jaw is an extremely rare condition accounting to less than 2% of all mucoepidermoid carcinomas. In the jaw, it occurs more commonly in mandible than maxilla. They are low-grade cancers and affect jaw as uni- or multi-locular radiographic lesions. Here we discuss a rare case of giant cystic primary intra-cystic mucoepidermoid carcinoma of the mandible which was excised in toto. Here we discuss the clinical features, radiological and histological characteristics of this rare lesion, and review the literature.

  20. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging of an isolated subcutaneous loin metastasis from primary papillary carcinoma of the thyroid

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Shibu, Deepu; Edathurthy, Radhakrishnan; Shinto, Ajit Sugunan

    2014-01-01

    Differentiated thyroid cancer frequently metastasizes but generally spreads to regional cervical lymph nodes and, in advanced cases, to the lungs and/or skeleton. Metastases to the skin/subcutaneous tissue are rare. We report 45-year-old male patient presented with a loin swelling which on biopsy showed a papillary carcinoma and referred for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) to find out the primary disease. PET/CT showed abnormal FDG uptake within a loin metastasis and right lobe thyroid nodule. Fine-needle aspiration from nodule showed papillary carcinoma. Because thyroid cancer can rarely metastasize to the skin, attention should be given to that region during interpretation of the images. He was advised total thyroidectomy and metastasis excision. PMID:24761062

  1. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging of an isolated subcutaneous loin metastasis from primary papillary carcinoma of the thyroid.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Shibu, Deepu; Edathurthy, Radhakrishnan; Shinto, Ajit Sugunan

    2014-04-01

    Differentiated thyroid cancer frequently metastasizes but generally spreads to regional cervical lymph nodes and, in advanced cases, to the lungs and/or skeleton. Metastases to the skin/subcutaneous tissue are rare. We report 45-year-old male patient presented with a loin swelling which on biopsy showed a papillary carcinoma and referred for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) to find out the primary disease. PET/CT showed abnormal FDG uptake within a loin metastasis and right lobe thyroid nodule. Fine-needle aspiration from nodule showed papillary carcinoma. Because thyroid cancer can rarely metastasize to the skin, attention should be given to that region during interpretation of the images. He was advised total thyroidectomy and metastasis excision.

  2. Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

    PubMed Central

    Ahmed, Maha Imam; Salahy, Eman-El; Tawfiq, Hassan; Khalifa, Ali; Hassan, Manal M.

    2004-01-01

    Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide – specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach. PMID:15665394

  3. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA–IIB Cervical Squamous Cell Carcinoma

    PubMed Central

    Liu, Yu; Zhao, Li-Jun; Li, Ming-Zhu; Li, Ming-Xia; Wang, Jian-Liu; Wei, Li-Hui

    2015-01-01

    Background: Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75–80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence. Methods: We performed a retrospective review of 296 patients diagnosed with Stage IA–IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy. Results: The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM. Conclusions: Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI

  4. A co-operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells.

    PubMed

    Edwards, Jennifer L; Brown, Eric J; Uk-Nham, Sang; Cannon, Janne G; Blake, Milan S; Apicella, Michael A

    2002-09-01

    Little is known about the pathogenesis of gonococcal infection within the lower female genital tract. We recently described the distribution of complement receptor 3 (CR3) on epithelia of the female genital tract. Our studies further indicate that CR3-mediated endocytosis serves as a primary mechanism by which N. gonorrhoeae elicits membrane ruffling and cellular invasion of primary, human, cervical epithelial cells. We have extended these studies to describe the nature of the gonococcus-CR3 interaction. Western Blot analysis demonstrated production of alternative pathway complement components by ecto- and endocervical cells which allows C3b deposition on gonococci and its rapid conversion to iC3b. Anti-iC3b and -factor I antibodies significantly inhibited adherence and invasion of primary cervical cells, suggesting that iC3b covalently bound to the gonococcus serves as a primary ligand for CR3 adherence. However, gonococcal porin and pili also bound to the I-domain of CR3 in a non-opsonic manner. Binding of porin and pili to CR3 were required for adherence to and invasion of cervical epithelia. Collectively, these data suggest that gonococcal adherence to CR3 occurs in a co-operative manner, which requires gonococcal iC3b-opsonization, porin and pilus. In conjunction, these molecules facilitate targeting to and successful infection of the cervical epithelium. PMID:12390350

  5. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

    PubMed Central

    van Dam, Peter A.; van Dam, Pieter-Jan H. H.; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A. A.; van Laere, Steven

    2016-01-01

    An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR < 0.1). Comparing to CCCLs 560 probe sets (481 unique genes) had a cancer cell-specific expression profile, and 315 of these genes (65%) were validated. GSEA identified 5 cancer hallmarks enriched in CCSs (P < 0.01 and FDR < 0.25) showing that deregulation of the cell cycle is a major component of cervical cancer biology. E2K identified a protein-protein interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

  6. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment.

    PubMed

    van Dam, Peter A; van Dam, Pieter-Jan H H; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A A; van Laere, Steven

    2016-01-19

    An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR < 0.1). Comparing to CCCLs 560 probe sets (481 unique genes) had a cancer cell-specific expression profile, and 315 of these genes (65%) were validated. GSEA identified 5 cancer hallmarks enriched in CCSs (P < 0.01 and FDR < 0.25) showing that deregulation of the cell cycle is a major component of cervical cancer biology. E2K identified a protein-protein interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

  7. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2016-10-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  8. Suppression of carbonyl reductase expression enhances malignant behaviour in uterine cervical squamous cell carcinoma: carbonyl reductase predicts prognosis and lymph node metastasis.

    PubMed

    Murakami, Akihiro; Fukushima, Chikako; Yoshidomi, Keiko; Sueoka, Kotaro; Nawata, Shugo; Yokoyama, Yoshihito; Tsuchida, Shigeki; Ismail, Endom; Al-Mulla, Fahd; Sugino, Norihiro

    2011-12-01

    Carbonyl reductase (CR) is an NADPH-dependent, mostly monomeric, cytosolic enzyme with broad substrate specificity for carbonyl compounds. CR appears to be involved in the regulation of tumour progression. However, molecular mechanisms of CR in tumour progression and clinical significance of CR status remain unclear in human uterine squamous cell carcinoma (SCC). Here, we investigated the clinical significance of CR using immunohistochemical analyses of human uterine cervical SCC tissues and how CR affects cancer cell behaviour in vitro. Paraffin sections from uterine cervical SCC tissues, FIGO stage Ib1-IIb (n = 67) were immunostained with anti-CR antibodies. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Sense and antisense CR cDNAs were transfected into a human uterine SCC cell line (SiHa) to investigate the role of CR in cancer cell invasion and metastasis. Immunohistochemical analyses showed that reduced CR expression patterns in primary cancer lesions were closely associated with a high incidence of pelvic lymph node metastasis, poor OS, and poor PFS. In an in vitro experiment, suppression of CR increased cancer cell invasion, secretion of MMP-2, -9 and cyclooxygenase-2 (COX-2) expression and decreased E-cadherin expression. On the other hand, over-expression of CR increased E-cadherin expression and decreased MMP-2, -9 secretion and COX-2 expression. The reduced CR expression pattern, as measured by immunohistochemistry, can be a useful predictor of lymph node metastasis and poor prognosis in patients with uterine SCC. This clinical result is supported by the in vitro data which show that suppression of CR expression promotes cancer cell invasion with decreased E-cadherin expression and increased MMP-2, -9 secretion.

  9. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

    PubMed Central

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

  10. A pure primary transitional cell carcinoma of the ovary: A rare case report with literature review.

    PubMed

    Chandanwale, Shirish S; Kamble, Tushar; Mishra, Neha; Kumar, Harsh; Jadhav, Rahul

    2016-01-01

    Primary transitional cell carcinoma (TCC) of the ovary is a rare and recently recognized subtype of ovarian surface epithelial-stromal cancer. Pure forms of the TCC ovary account for only 1% of surface epithelial carcinomas. The clinical presentation is indistinguishable from other types of ovarian cancers. They have a favorable response to chemotherapy than other surface epithelial cancers. We report a case of 55-year-old woman who presented with a hard mass in the abdomen. Computed tomography-diagnosed it as a carcinoma of the ovary. Tumor was immunoreactive with Wilms' tumor protein-1 and nonreactive with cytokeratin 7 (CK7) and CK20. Histopathology diagnosis of primary TCC of the ovary was made. These tumors are needed to be differentiated from metastatic TCC from other sites and undifferentiated carcinomas of ovaries. Clinical features and immunohistochemistry are helpful. Surgical resection is the primary therapeutic approach followed by standardized chemotherapy. PMID:27127747

  11. Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

    PubMed

    Ansari, Mahsa; Azmoodeh Ardalan, Farid; Najafi, Masoumeh; Goodarzi, Azadeh; Ghanadan, Alireza

    2015-12-01

    Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management. PMID:26749237

  12. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  13. Primary leptomeningeal melanoma of the cervical spine mimicking a meningioma-a case report.

    PubMed

    Marx, Sascha; Fleck, Steffen K; Manwaring, Jotham; Vogelgesang, Silke; Langner, Soenke; Schroeder, Henry W S

    2014-08-01

    Background and Importance Primary leptomeningeal melanoma (PLM) is highly malignant and exceedingly rare. Due to its rarity, diagnostic and treatment paradigms have been slow to evolve. We report the first case of a PLM that mimics a cervical spine meningioma and then discuss the current clinical, radiologic, and pathologic diagnostic methodologies as well as expected outcomes related to this disease. Clinical Presentation A 54-year-old woman presented a dural-based extramedullary solid mass ventral to the C2-C3 spinal cord causing spinal cord compression without cord signal changes, characteristic of meningioma. Intraoperative microscopic inspection revealed numerous black spots littering the surface of the dura; the tumor itself was yellow in appearance and had a soft consistency. Pathologic analysis of the specimen revealed a malignant melanin-containing tumor. No primary site was found, so a diagnosis of primary leptomeningeal melanoma was made, and the patient subsequently received interferon therapy. To date (2 years postoperatively), no local or systemic recurrence of the tumor has been identified. Conclusion As with most rare tumors, case reports constitute the vast majority of references to PLM. Only an increased awareness and an extensive report of each individual case can help diagnose and clarify the nature of PLM. Clinicians need to be aware of such malignant conditions when diagnosing benign tumoral lesions of the spine such as meningiomas.

  14. Design and optimization of non-clogging counter-flow microconcentrator for enriching epidermoid cervical carcinoma cells.

    PubMed

    Tran-Minh, Nhut; Dong, Tao; Su, Qianhua; Yang, Zhaochu; Jakobsen, Henrik; Karlsen, Frank

    2011-02-01

    Clogging failure is common for microfilters in living cells concentration; for instance, the CaSki Cell-lines (Epidermoid cervical carcinoma cells) utilizing the flat membrane structure. In order to avoid the clogging, counter-flow concentration units with turbine blade-like micropillar are proposed in microconcentrator design. Due to the unusual geometrical-profiles and extraordinary microfluidic performance, the cells blocking does not occur even at permeate entrances. A counter-flow microconcentrator was designed, with both processing layer and collecting layer arranged in terms of the fractal based honeycomb structure. The device was optimized by coupling Artificial Neuron Network (ANN) and Computational Fluid Dynamics (CFD). The excellent concentration ratio of a final microconcentrator was presented in numerical results.

  15. Primary cervical cancer screening with an HPV mRNA test: a prospective cohort study

    PubMed Central

    Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve; Skjeldestad, Finn Egil

    2016-01-01

    Objectives To assess the performance of a 5-type human papillomavirus (HPV) messenger RNA (mRNA) test in primary screening within the framework of the Norwegian population-based screening programme. Design Nationwide register-based cohort study. Setting In 2003–2004, general practitioners and gynaecologists recruited 18 852 women for participation in a primary screening study with a 5-type HPV mRNA test. Participants After excluding women with a history of abnormal smears and with cervical intraepithelial neoplasia grade 2 (CIN2+) before or until 3 months after screening, 11 220 women aged 25–69 years were eligible for study participation. The Norwegian Cancer Registry completed follow-up of CIN2+ through 31 December 2009. Interventions Follow-up according to the algorithm for cytology outcomes in the population-based Norwegian Cervical Cancer Screening Programme. Main outcome measures We estimated cumulative incidence of CIN grade 3 or worse (CIN3+) 72 months after the 5-type HPV mRNA test. Results 3.6% of the women were HPV mRNA-positive at baseline. The overall cumulative rate of CIN3+ was 1.3% (95% CI 1.1% to 1.5%) through 72 months of follow-up, 2.3% for women aged 25–33 years (n=3277) and 0.9% for women aged 34–69 years (n=7943). Cumulative CIN3+ rates by baseline status for HPV mRNA-positive and mRNA-negative women aged 25–33 years were 22.2% (95% CI 14.5% to 29.8%) and 0.9% (95% CI 0.4% to 1.4%), respectively, and 16.6% (95% CI 10.7% to 22.5%) and 0.5% (95% CI 0.4% to 0.7%), respectively, in women aged 34–69 years. Conclusions The present cumulative incidence of CIN3+ is similar to rates reported in screening studies via HPV DNA tests. Owing to differences in biological rationale and test characteristics, there is a trade-off between sensitivity and specificity that must be balanced when decisions on HPV tests in primary screening are taken. HPV mRNA testing may be used as primary screening for women aged 25–33 years and

  16. SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

    SciTech Connect

    Cao, Y; Li, R; Chi, Z; Zhu, S

    2014-06-01

    Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose received by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.

  17. Higher expression and activity of metalloproteinases in human cervical carcinoma cell lines is associated with HPV presence.

    PubMed

    da Silva Cardeal, Laura Beatriz; Brohem, Carla Abdo; Corrêa, Tatiana Caroline Silveira; Winnischofer, Sheila Maria Brochado; Nakano, Fabio; Boccardo, Enrique; Villa, Luisa Lina; Sogayar, Mari Cleide; Maria-Engler, Silvya Stuchi

    2006-10-01

    Matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MT1-MMP are required for basement membrane degradation in cervical carcinoma. We evaluated the expression and activity of MMPs and their inhibitors RECK and TIMP-2 in 3 human invasive cervical carcinoma cell lines. Two HPV16-positive cell lines (SiHa and CaSki) and an HPV-negative cell line (C33A) were cultured either onto a type-I collagen gel, Matrigel, or plastic, to recreate their three-dimensional growth environment and evaluate the expression of these genes using quantitative real-time PCR. We also analyzed the gelatinolytic activity of MMP-2 and MMP-9 by zymography. We found that HPV (human papillomavirus)-positive cell lines express higher levels of MMP-2, MT1-MMP, and TIMP-2 than the HPV negative cell line. In addition, MMP-9 was expressed at very low levels in both HPV-negative and HPV-positive cell lines. We also observed that the expression of the RECK gene is higher in CaSki cells, being associated with higher pro-MMP-2 activity. Furthermore, Matrigel substrate influences MMP-2 expression in both SiHa and CaSki cells. On the other hand, we found that type-I collagen gel, but not Matrigel, can enhance pro-MMP-2 activity in all cell lines. Our results suggest that the presence of HPV is related to increased expression of MMP-2, MT1-MMP, and TIMP-2, and that pro-MMP-2 activity is higher in HPV-positive than in HPV-negative cells.

  18. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells.

    PubMed

    Kim, Dong-Hyun; Jarvis, Roger M; Allwood, J William; Batman, Gavin; Moore, Rowan E; Marsden-Edwards, Emma; Hampson, Lynne; Hampson, Ian N; Goodacre, Royston

    2010-12-01

    It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV.

  19. Correlation Between Platelet and Hemoglobin Levels and Pathological Characteristics and Prognosis of Early-Stage Squamous Cervical Carcinoma

    PubMed Central

    Li, Xiaowei; Tan, Cheng; Zhang, Wanxuan; Zhou, Jingyi; Wang, Zhiqi; Wang, Shijun; Wang, Jianliu; Wei, Lihui

    2015-01-01

    Background We sought to determine the effect of pre-operative hemoglobin (HGB) and platelet (PLT) levels on the clinical features and prognosis of early-stage squamous cervical carcinoma (SCC). Material/Methods We performed a retrospective analysis of 380 patients with SCC who underwent hysterectomy and pelvic lymphadenectomy. SCC was confirmed post-operatively by pathological diagnosis. The relations between HGB and PLT levels and clinicopathological characteristics were observed, and a Cox regression analysis was performed to determine their influence on survival. Results There were significant differences in tumor staging, tumor diameter, and lymphatic metastasis between the 69 patients with PLT levels >300×109/L and the 311 patients with PLT levels ≤300×109/L (P<0.05). Tumor staging, extent of differentiation, and lymphatic metastasis were significantly different between 134 patients with HGB levels <120 g/L and 246 patients with HGB levels ≥120 g/L (P<0.05). The overall survival rate in the group with PLT levels >300×109/L was lower than that in the group with PLT levels ≤300 × 109/L, but this difference was not significant. The overall survival rate in the group with HGB levels <120 g/L was significantly lower than that in the group with HGB levels ≥120 g/L (P<0.05), and the overall survival rate in the group with PLT levels >300×109/L and HGB levels <120 g/L was significantly lower than that in the group with PLT levels ≤300×109/L and HGB levels ≥120 g/L (P<0.05). According to Cox regression analysis, a pre-operative HGB level <120 g/L was considered a separate risk factor affecting prognosis. Conclusions Close attention must be paid to pre-operative PLT and HGB levels, and anemia should be remedied to facilitate the treatment of cervical carcinoma. PMID:26670918

  20. Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international review.

    PubMed

    Suárez, Carlos; Barnes, Leon; Silver, Carl E; Rodrigo, Juan P; Shah, Jatin P; Triantafyllou, Asterios; Rinaldo, Alessandra; Cardesa, Antonio; Pitman, Karen T; Kowalski, Luiz P; Robbins, K Thomas; Hellquist, Henrik; Medina, Jesus E; de Bree, Remco; Takes, Robert P; Coca-Pelaz, Andrés; Bradley, Patrick J; Gnepp, Douglas R; Teymoortash, Afshin; Strojan, Primož; Mendenhall, William M; Eloy, Jean Anderson; Bishop, Justin A; Devaney, Kenneth O; Thompson, Lester D R; Hamoir, Marc; Slootweg, Pieter J; Vander Poorten, Vincent; Williams, Michelle D; Wenig, Bruce M; Skálová, Alena; Ferlito, Alfio

    2016-10-01

    The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0-14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.

  1. Identification of high-risk human papillomavirus (hrHPV)-associated genes in early stage cervical squamous cell carcinomas.

    PubMed

    Hu, Y; Liu, Y; Liu, C-B; Ling, Z-Q

    2011-01-01

    This retrospective study investigated gene expression in tumour samples from 38 patients with early stage human papillomavirus (HPV)-associated cervical squamous cell carcinoma (CSCC). The patients were divided into two groups based on the presence of viral markers of HPV16 or HPV18 infection. Gene expression profiles of tumour samples and the corresponding normal cervical epithelium were analysed using cDNA microarrays. Several genes showed differential expression between the two groups of HPV-infected CSCC patients, although seven genes showed similar changes in both groups. The four genes encoding cyclin-dependent kinase inhibitor 2A, matrix metallopeptidase 9, laminin γ-1, and epidermal growth factor receptor were up-regulated, and the three genes encoding transforming growth factor β receptor 1, interleukin-1α and insulin-like growth factor-binding protein 6 were down-regulated, in both HPV16(+) and HPV18(+) CSCC. These proteins are involved in cell proliferation, cell structure and cell attachment, so their expression might be involved in the mechanism of HPV-induced carcino genesis. A clearer understanding of HPV type-specific gene expression might aid diagnosis and treatment.

  2. Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    SciTech Connect

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-06-10

    Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  3. Placental alkaline phosphatase isoenzyme expression by the non-HeLa DoT cervical-carcinoma cell line.

    PubMed Central

    Kottel, R H; Fishman, W H

    1981-01-01

    Expression of the oncodevelopmental protein, placental alkaline phosphatase, was observed in DoT cells, an epidermoid cell line derived from cervical carcinoma. Under normal conditions of growth in vitro, biochemical inhibition, cytochemical and immunological studies revealed that these cells express the term-placental (Regan) isoenzyme. Thus alkaline phosphatase activity was observed to be heat-stable and inhibited by L-phenylalanine. These properties, supported by immunoelectrophoretic analysis using antisera specific for liver, intestinal or term-placental isoenzymes, identified the isoenzyme as placental type. DoT cells treated with prednisolone (1 microgram/ml) increased total alkaline phosphatase specific activity. This activity was also identified as term-placental phosphatase isoenzyme. On the other hand, treatment of the same cells with sodium butyrate (1 mM) did not induce increased activity of the term-placental isoenzyme, an unexpected observation. As a result of these studies, DoT cells are proposed as a representative cell line for studies of the regulation of oncodevelopmental gene expression in human tumour cells of cervical origin. Images Fig. 2. Fig. 3. PMID:7342975

  4. Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers—Hepatocellular Carcinoma and Cervical Cancer

    PubMed Central

    Hang, Dong; Han, Jing; Jiang, Jie; Song, Ci; Liu, Yao; Liu, Jibin; Liu, Li; Zhu, Liguo; Chen, Jianguo; Zhai, Xiangjun; Xie, Shuanghua; Hu, Zhibin; Shen, Hongbing; Dai, Min; Li, Ni

    2015-01-01

    Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03–1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09–1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer. PMID:26147888

  5. Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma

    PubMed Central

    2012-01-01

    Aim SOX4, as a member of the SRY-related HMG-box (SOX) transcription factor family, has been demonstrated to be involved in tumorigenesis of many human malignancies; however, its role in primary gallbladder carcinoma (PGC) is still largely unknown. The aim of this study was to investigate SOX4 expression in PGC and its prognostic significance. Methods From 1997 to 2006, 136 patients underwent resection for PGC. The median follow-up was 12.8 months. Immunostainings for SOX4 were performed on these archival tissues. The correlation of SOX4 expression with clinicopathological features including survival was analyzed. Results SOX4 was expressed in 75.0% (102/136) of PGC but not in the normal epithelium of the gallbladder. In addition, the over-expression of SOX4 was significantly associated with low histologic grade (P = 0.02), low pathologic T stage (P = 0.02), and early clinical stage (P = 0.03). The levels of SOX4 immunostainings in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Moreover, Kaplan-Meier curves showed that SOX4 over-expression was significantly related to better overall (P = 0.008) and disease-free survival (P = 0.01). Furthermore, multivariate analyses showed that SOX4 expression was an independent risk factor for both overall (P = 0.03, hazard ratio, 3.682) and disease-free survival (P = 0.04, hazard ratio, 2.215). Conclusion Our data indicate for the first time that the over-expression of SOX4 in PGC was significantly correlated with favorable clinicopathologic features and was an independent prognostic factor for better overall and disease-free survival in patients. Therefore, SOX4 might be an auxiliary parameter for predicting malignant behavior for PGC. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1534825818694957. PMID:22510499

  6. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  7. Diagnostic Accuracy of MRI, DWI MRI, FDG-PET/CT and FEC PET/CT in the Detection of Lymph Node Metastases in Surgically Staged Endometrial and Cervical Carcinoma

    ClinicalTrials.gov

    2016-01-21

    Surgically Staged Endometrial and Cervical Carcinoma; Cervical Cancer: Invasive Disease, FIGO Stage 1B1 or Higher; Endometrial Cancer:; Stage 1A With Myometrial Invasion or Any Higher Stage and Grade 3; Stage 1A With Myometrial Invasion or Any Other Higher Stage and Serous Papillary or Clear Cell Sub-types; Stage II Disease or Above and Any Histology Grade

  8. Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review.

    PubMed

    Acosta, Andres M; Wiley, Elizabeth Louise

    2016-10-01

    Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component. PMID:27684986

  9. A Rare Presentation of Primary Nasopharyngeal Carcinoma (NPC) in Mediastinum

    PubMed Central

    Fathi, Afshin; Amani, Firuz; Davoodi, Mohammad; Bahadoram, Sara; Bahadoram, Mohammad

    2016-01-01

    Introduction Nasopharyngeal carcinoma among the children has been rare accounting for only 1% of all pediatric malignancies. Both genetic and environmental factors have contributed to the development of nasopharyngeal carcinoma. Among the children there was a higher rate of undifferentiated histology. The mean age of nasopharyngeal carcinoma diagnosis has been 11 years old age; and the most common site was nasopharynx. Palpable lymphadenopathy, dysphasia and neural defect were common associated signs. Case Presentation A 15-year-old boy has presented with a mass that located near by the heart in the left side of mediastinum with invasion to anterior mediastinum from two years ago. In biopsy, nasopharyngeal carcinoma, non-keratinizing type, has diagnosed while there was no involvement of nasopharyngeal region. Patient has treated by 70 Gy (2.0 Gy/fraction) radiotherapy plus concomitant chemotherapy with base of docetaxel. But the mass had no regression. Then, the patient has treated with Cisplatin 100 mg/m2 IV on days 1, 22, and 43 with radiation, then cisplatin 80 mg/m2 IV on day 1 plus fluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1 - 4 every 4wk for 3 cycles and after remission interferon beta has added to treatment for 6 months duration as a maintenance therapy. After 1 year follow up; the patient was in complete remission. In the course of therapy, only hypothyroidism has occurred. Conclusions Nasopharyngeal carcinoma in childhood, without nasopharyngeal involvement, initially could be detected in other sites such as pericardium. Also good results could be respected by cisplatin and 5-fluorouracil based neoadjuvant chemotherapy before radiotherapy plus interferon beta as a maintenance therapy in childhood aggressive nasopharyngeal carcinoma. PMID:27761207

  10. [Conservative treatment of chyle fistula of the neck following a reintervention of cervical bilateral lymphectomy for medullary carcinoma of the thyroid. Case report].

    PubMed

    Giove, Eleonora; Merlicco, Domenico; Nacchiero, Eleonora; Marzaioli, Rinaldo

    2010-01-01

    Chyle fistula is an uncommon serious complication of neck surgery, occurring in 1-3% of radical neck dissections. An untreated chyle leak is a potentially dangerous condition that may rarely lead to hypovolemia, hyponatremia, hypochloremia, hypoproteinemia and lymphopenia. Anatomic variants of the terminal portion of the thoracic duct and suction drainage in the neck wound play a primary role in causing this kind of lesion. Poor is the literature concerning chyle fistula, due to its rarity, and mostly case reports; still debated--prevalently empiric--is the management of this disease. The Authors report a case of chyle fistula following a reintervention of cervical bilateral lymphectomy for medullary carcinoma of the thyroid in a 75 years old female. In the reported case the chyle fistula was successfully treated conservatively, in early post-operative period with a low-fat diet and total parenteral nutrition, definitely followed by sclerosant therapy. The injection of a sclerosant agent (4 g of sterile medical talc diluted in isotonic sodium chloride solution) into the supraclavicular wound bed, through the drainage tube (clamped for 2 hours), determined rapid decline in fistula output, hence obviating surgical intervention.

  11. GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

    PubMed

    Deftereos, Georgios; Sanguino Ramirez, Angela M; Silverman, Jan F; Krishnamurti, Uma

    2015-09-01

    GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; P<0.0001) and mammaglobin (58.9%; P<0.0001), whereas staining patterns were similar for all the histologic subtypes examined. Staining scores were determined by multiplying the percentage of cancer cells staining with an intensity score of 1+, 2+, or 3+ (range, 0 to 300). In non-triple-negative carcinomas, GATA3 showed a mean score of 273.7, higher than GCDFP-15 (107.5; P<0.0001) and mammaglobin (147.7; P<0.0001). In triple-negative breast carcinomas (n=28), GATA3 showed a sensitivity of 60.7%, greater than GCDFP-15 (17.9%; P=0.0022) and mammaglobin (7.1%; P<0.0001). These results were consistent irrespective of the subtype examined. In breast carcinoma cytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; P<0.0001) and mammaglobin (45%; P<0.0001). None of the metastatic endometrial or ovarian carcinomas were positive for GATA3. Although GATA3 expression correlates with ER expression in breast, no correlation is observed in gynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast.

  12. The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis

    PubMed Central

    Felix, Juan C.; Lacey, Michael J.; Lenhart, Gregory M.; Spitzer, Mark; Kulkarni, Rucha

    2016-01-01

    Abstract Background: Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. Methods: A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. Results: In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. Conclusions: Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates

  13. Prognostic value of microRNAs in cervical carcinoma: a systematic review and meta-analysis

    PubMed Central

    Dai, Shengkang; Lu, Yan; Long, Ying; Lai, Yuehua; Du, Ping; Ding, Nan; Yao, Desheng

    2016-01-01

    This systematic review is written to investigate the outcome of cervical cancer. A comprehensive search of PubMed and EMBASE was performed to identify eligible studies. Nineteen studies from thirteen articles with a total of 1,310 participants were included in this meta-analysis. Overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) as a prognosis for cervical cancer were extracted and calculated, if available. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using STATA (version 12.0), resulting in the pooled HRs 0.70 (95% CI: 0.51–0.97) for OS, 1.02 (95% CI: 0.53–1.98) for DFS, and 0.56 (95% CI: 0.40–0.77) for RFS. The results indicated that cervical cancer patients with decreased microRNA expression were associated with shorter OS and RFS. It suggested that microRNAs might be promising markers for predicting the survival rate of cervical cancer. PMID:27177085

  14. Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an analysis of 376 cases in an Eastern Chinese population.

    PubMed

    Liu, S; Ow, A; Ruan, M; Yang, W; Zhang, C; Wang, L; Zhang, C

    2014-06-01

    Mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm that originates most commonly in the salivary glands. The present study aimed to provide new information on prognostic factors in patients with salivary gland MEC. A retrospective analysis of the medical records of patients diagnosed with primary salivary gland MEC between 2003 and 2010 was conducted. The incidence of MEC in the minor salivary glands (62.2%) was almost twice that in the major salivary glands (37.8%). The most frequently affected sites were the parotid gland and palate. Lymph node metastasis was reported more frequently in male than female patients (P = 0.02), in high-grade than low/intermediate grade lesions (P < 0.001), and in lesions involving the submandibular gland (P < 0.001). The disease-free survival (DFS) at 5 years was 80.47%, with rates of 98.0%, 86.5%, and 38.5% for low-, intermediate-, and high-grade tumours, respectively. Among various clinicopathological factors, the only independent prognostic factor was histological grade (P < 0.001). Primary tumour site and histological grade are two important factors affecting cervical lymph node metastasis. Histological grade is the only independent factor affecting survival beyond tumor lymph node metastasis (TNM) staging in salivary gland MEC. Further advances in therapy are needed to improve the outcomes for patients with high-grade lesions. PMID:24568836

  15. Primary squamous cell carcinoma of the breast: a case report and review of literature

    PubMed Central

    Seddik, Youssef; Brahmi, Sami Aziz; Afqir, Said

    2015-01-01

    Primary squamous cell carcinoma is a well known malignancy of the skin and other organs composed of squamous cells, which are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceedingly uncommon phenomen and the management of this type of disease is still unclear. We report the case of a 43-year-old Moroccan woman, without significant medical history, presented an infected mass of 9 cm in the left breast associated with ipsilateral axillary lymphadenopathy. The mass's surgical biopsy revealed a triple negative primary squamous cell carcinoma of the breast. She underwent a neoadjuvant chemotherapy using 5 Fluoro-Uracil and platinum. After three courses, she presented a contralateral breast progression and apparition of metastasis at D10. She received one course of a palliative chemotherapy based on weekly paclitaxel stopped because of her peformans status deterioration. She died 7 months after her admission. PMID:27386028

  16. Analysis of ROC: The value of HPV16 E6 protein in the diagnosis of early stage cervical carcinoma and precancerous lesions

    PubMed Central

    Sun, Li; Xu, Shubin; Liang, Lei; Zhao, Liang; Zhang, Lei

    2016-01-01

    Cervical carcinoma is a multifactorial malignant tumor and diagnosis is therefore crucial. The aim of the present study was to examine the value of E6 oncoprotein, in human papillomavirus type 16 (HPV16), in the diagnosis of early stage cervical carcinoma and precancerous lesions. Receiver operating characteristic curve was used to analyze accuracy of diagnosis. A total of 124 patients infected with HPV16 were included in the study. The patients had an average age of 46.7±6.9 years and duration of disease of 10.5±3.4 months. To determine the expression level of HPV16 E6 the immunohistochemical Elivision method was performed. Proportion/horizon positive cells were used to count the cells, and pathologic diagnosis was employed for analysis of the results. The average follow-up time was 2.6±0.7 years. Sensitivity and specificity of diagnosing HPV16 E16 at 1 and 2 years, respectively, were calculated. The diagnostic rate of cervical carcinoma increased with time, and the positive expression of HPV16 E6 was also increased with the development of the disease. Differences among groups were statistically significant (P<0.05). Sensitivity, specificity and accuracy (AUC) of HPV16 E6 diagnosis improved with time, and the differences were statistically significant (P<0.05). Thus, HPV16 E6 oncoprotein can be used as an indicator with good sensitivity and specificity to diagnose early cervical carcinoma and precancerous lesions. The results therefore showed that accuracy increased with the development of the disease. PMID:27588123

  17. Primary Hepatic Small-Cell Carcinoma Developed during Antiviral Treatment for Chronic Hepatitis B

    PubMed Central

    Kim, Suk Bae

    2015-01-01

    Previously reported cases of primary hepatic small-cell carcinoma were all detected at progressed state with associated symptoms. Therefore, the natural course of primary hepatic small-cell carcinoma remains unknown. This case shows the natural course of primary hepatic small-cell carcinoma. We detected a 1.2 cm hypodense nodule 6 months ago in a patient with cirrhosis who had been taking entecavir. It was suspected to be a regenerating or degenerating nodule. Three months later, liver computed tomography (CT) revealed that the mass was increased to 2.1 cm with the same characteristics. The patient wanted to do a follow-up CT scan after 3 months instead of a biopsy. Another 3 months later, the mass was markedly increased, involving the whole left lobe and was confirmed as small-cell carcinoma on biopsy. Here, we report the first case of primary hepatic small-cell carcinoma developed during treatment for chronic hepatitis B with cirrhosis. PMID:26951743

  18. Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

    PubMed

    Hawighorst, H; Knapstein, P G; Weikel, W; Knopp, M V; Zuna, I; Knof, A; Brix, G; Schaeffer, U; Wilkens, C; Schoenberg, S O; Essig, M; Vaupel, P; van Kaick, G

    1997-11-01

    Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic

  19. Inactivation of PTCH1 is associated with the development of cervical carcinoma: clinical and prognostic implication.

    PubMed

    Chakraborty, Chandraditya; Dutta, Sankhadeep; Mukherjee, Nupur; Samadder, Sudip; Roychowdhury, Anirban; Roy, Anup; Mondal, Ranajit Kumar; Basu, Partha; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2015-02-01

    The aim of this study was to analyze the alterations of PTCH1 (deletion/promoter methylation/mutation/expression) during the development of cervical cancer (CACX). For this purpose, deletion/methylation of PTCH1 were analyzed in HPV16 positive exfoliated asymptomatic cervical swabs (n = 74), cervical intraepithelial neoplasia (CIN) (n = 32), CACX (n = 174) samples, and two CACX cell lines. The deletion of PTCH1 increased significantly from CIN (11.5%) to stage I/II (42%) and comparable in stage III/IV (46%). Low frequency (14-16%) of PTCH1 methylation was seen in the asymptomatic exfoliated cervical cells and in the normal epithelium adjacent to the tumor followed by a significant increase in CIN (31%) to stage I/II (57%) and comparable in stage III/IV (58%). The overall alterations (deletion/methylation) of PTCH1 significantly increased from CIN (34%) to stage I/II (70%) and comparable in stage III/IV (69%). Interestingly, in the normal epithelium, methylation of PTCH1 was high in basal/parabasal layers (83%), followed by decrease in the spinous layer (33 %), and showed significant inverse correlation with its expression. Reduced expression of PTCH1 seen in tumors showed a significant association with its alterations (deletion/methylation). The expression pattern of PTCH1 showed an inverse correlation with the nuclear expression of GLI1 in the normal epithelium as well as in the tumors. High nuclear expression of HPV16, E6, and E7 were seen in basal/parabasal layers of the normal epithelium and also in tumors. The PTCH1 alterations (deletion and/or methylation) in tumors and its methylation in adjacent normal epithelium were associated with poor prognosis of patients. Thus, our data suggests that activation of the Hedgehog pathway due to PTCH1 inactivation along with HPV infection is important in CACX development. PMID:25330948

  20. Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma.

    PubMed

    Burt, Michael; Madan, Rashna; Fan, Fang

    2016-10-01

    We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine chromatin and small nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule out metastatic neuroendocrine disease. PMID:27342908

  1. Fertility-Preserving Surgery in Patients with Early Stage Cervical Carcinoma

    PubMed Central

    Kardakis, Spyridon

    2012-01-01

    Fertility preservation is an important issue for patients in reproductive age with early stage cervical cancer. In view of recent developments, our purpose was to review and discuss available surgical alternatives. A literature search was conducted using PUBMED, including papers between 1980 and December 2011. In patients with stage IA1 cervical cancer, conization is a valid alternative. Patients with stage IA2-IB1 disease can be conservatively treated by radical trachelectomy. This is as well-established conservative approach and appears to be safe and effective in allowing a high chance of conception. Prematurity is the most serious issue in pregnancies following trachelectomy. Less invasive options such as simple trachelectomy or conization seem to be feasible for stages IA2-IB1, but more and better evidence is needed. Neoadjuvant therapy might allow conservative surgery to be performed also in patients with more extensive lesions. Ovarian transposition is important when adjuvant radiation is needed. In conclusion, available literature shows that there are interesting fertility-sparing treatment alternatives to the “golden standard” for the management of early cervical cancer in young women. PMID:23320192

  2. High expression of flotillin-2 is associated with poor clinical survival in cervical carcinoma

    PubMed Central

    Liu, Yaqiong; Lin, Li; Huang, Zijian; Ji, Bing; Mei, Shanshan; Lin, Ying; Shen, Zhuanxing

    2015-01-01

    Aims: To investigate the expression and clinical significance of flotillin-2 (FLOT2) in cervical cancer (CC). Methods: We examined FLOT2 mRNA levels in 10 pairs of cervical cancer and adjacent normal tissues. Immunohistochemistry was performed to analyze FLOT2 protein expression in 115 archived cervical cancer samples. The association between FLOT2 levels, clinicopathologic factors and prognosis was analyzed statistically as well. Results: The cancer tissues of CC patients had clearly increased expression of FLOT2 at mRNA level as compared to adjacent nontumorous tissues. Survival analysis of CC patients indicated that FLOT2 expression was significantly associated with poor overall and local recurrence-free survival (P = 0.025 and P = 0.028, respectively). Moreover, FLOT2 expression was significantly correlated with clinical stage, tumor differentiation, and lymph nodes metastasis. Multivariate analysis revealed that FLOT2 expression was an independent prognostic factor for overall survival in CC patients. Conclusion: FLOT2 may serve as an oncogene in the development of CC, and may serve as a clinicopathologic biomarker for prognosis in CC patients. PMID:25755754

  3. Entrance of the Tat protein of HIV-1 into human uterine cervical carcinoma cells causes upregulation of HPV-E6 expression and a decrease in p53 protein levels

    PubMed Central

    Barillari, Giovanni; Palladino, Clelia; Bacigalupo, Ilaria; Leone, Patrizia; Falchi, Mario; Ensoli, Barbara

    2016-01-01

    The infection of uterine cervical epithelial cells by oncogenic, high-risk human papilloma viruses (HR-HPVs) may lead to the development of cervical carcinoma. Of note, the incidence of this tumor is significantly increased in women infected by both HR-HPV and human immunodeficiency virus (HIV)-1. In this regard, previous studies have linked the HIV-1 Tat protein, a trans-activator of viral gene expression, to the pathogenesis of HIV-associated malignancies. In particular, it has been shown that upon its release by acutely infected cells, Tat protein can enter human cells, thus modifying their phenotype. Based on these findings, the present study evaluated whether extracellular Tat protein could be taken up by human uterine cervical carcinoma cells, and whether this could affect the expression of HPV (E6 or E7) or cellular (p16 or p53) molecules, which are key to cervical carcinoma development or progression. The results indicated that extracellular, biologically active HIV-1 Tat protein is taken up by human uterine cervical carcinoma cells, and that this is followed by an increase in the expression of the E6 protein of HPV, and by a reduction in the protein levels of the cellular oncosuppressor p53. Since p53 loss is associated with cell dedifferentiation and immortalization, these findings suggest a possible link between extracellular Tat protein and the high incidence and clinical aggressiveness of uterine cervical carcinoma observed in HIV/HPV doubly infected women.

  4. HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

    PubMed Central

    Cardeal, Laura Beatriz da Silva; Boccardo, Enrique; Termini, Lara; Rabachini, Tatiana; Andreoli, Maria Antonieta; di Loreto, Celso; Filho, Adhemar Longatto; Villa, Luisa Lina; Maria-Engler, Silvya Stuchi

    2012-01-01

    Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome. PMID:22438955

  5. HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis.

    PubMed

    Cardeal, Laura Beatriz da Silva; Boccardo, Enrique; Termini, Lara; Rabachini, Tatiana; Andreoli, Maria Antonieta; di Loreto, Celso; Longatto Filho, Adhemar; Villa, Luisa Lina; Maria-Engler, Silvya Stuchi

    2012-01-01

    Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.

  6. Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

    PubMed Central

    Schneider, Torben; Solanky, Bhavana S.; Yiannakas, Marios C.; Altmann, Dan R.; Wheeler-Kingshott, Claudia A. M.; Peters, Amy L.; Day, Brian L.; Thompson, Alan J.; Ciccarelli, Olga

    2015-01-01

    Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel 1H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q

  7. Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis.

    PubMed

    Abdel-Aziz, Khaled; Schneider, Torben; Solanky, Bhavana S; Yiannakas, Marios C; Altmann, Dan R; Wheeler-Kingshott, Claudia A M; Peters, Amy L; Day, Brian L; Thompson, Alan J; Ciccarelli, Olga

    2015-06-01

    Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q

  8. SU-E-T-36: An Investigation of the Margin From CTV to PTV Using Retraction Method for Cervical Carcinoma

    SciTech Connect

    Wu, D; Chen, J; Hao, Y; Liao, C; Huang, Y; Mo, Y; Wei, Y

    2014-06-01

    Purpose: This work employs the retraction method to compute and evaluate the margin from CTV to PTV based on the influence of target dosimetry of setup errors during cervical carcinoma patients treatment. Methods: Sixteen patients with cervical cancer were treated by Elekta synergy and received a total of 305 KV-CBCT images. The iso-center of the initial plans were changed according to the setup errors to simulate radiotherapy and then recalculated the dose distribution using leaf sequences and MUs for individual plans. The margin from CTV to PTV will be concluded both by the method of retracting (Fixed the PTV of the original plan, and retract PTV a certain distance defined as simulative organization CTVnx. The minimum distance value from PTV to CTVnx which get specified doses, namely guarantee at least 99% CTV volume can receive the dose of 95%, is the margin CTV to PTV we found) and the former formula method. Results: (1)The setup errors of 16 patients in X, Y and Z directions were(1.13±2.94) mm,(−1.63±7.13) mm,(−0.65±2.25) mm. (2) The distance between CTVx and PTV was 5, 9 and 3mm in X, Y and Z directions According to 2.5+0.7σ. (3) Transplantation plans displayed 99% of CTVx10- CTVx7 and received 95% of prescription dose, but CTVx6- CTVx3 departed from standard of clinic.In order to protect normal tissues, we selected 7mm as the minimum value of the margin from CTV to PTV. Conclusion: We have test an retraction method for the margin from CTV to PTV evaluation. The retraction method is more reliable than the formula method for calculating the margin from the CTV to the PTV, because it represented practice of treatment, and increasing a new method in this field.

  9. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    PubMed

    Lau, Yat Ming; Cheung, Tak Hong; Yeo, Winnie; Mo, Frankie; Yu, Mei Yung; Lee, Kun Min; Ho, Wendy C S; Yeung, Apple C M; Law, Priscilla T Y; Chan, Paul K S

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  10. Primary salivary duct carcinoma of the lung, mucin-rich variant.

    PubMed

    Fishbein, Gregory A; Grimes, Brandon S; Xian, Rena R; Lee, Jay M; Barjaktarevic, Igor; Xu, Haodong

    2016-01-01

    Primary salivary gland-type lung cancer is a heterogeneous group of neoplasms arising from the seromucinous glands of the respiratory tract. Histopathologically, they are identical to salivary gland neoplasms of the head and neck. While mucoepidermoid carcinoma and adenoid cystic carcinoma are overwhelmingly the most common subtypes found in the lung, reports of uncommon subtypes can be found in the literature. We report a case of a 73-year-old woman with primary lung salivary duct carcinoma, mucin-rich variant--an exceedingly rare subtype of an already rare malignant salivary-type neoplasm. One case of primary lung salivary duct carcinoma has been reported in the literature; however, the mucin-rich variant has never been described in the lung. Furthermore, the tumor in our case bears a rare BRAF G464V mutation. To our knowledge, this is the first reported case of a BRAF G464V mutation detected in a salivary duct carcinoma or any other salivary-type neoplasm.

  11. Disagreement between Human Papillomavirus Assays: An Unexpected Challenge for the Choice of an Assay in Primary Cervical Screening

    PubMed Central

    Ejegod, Ditte Møller; Rygaard, Carsten; Lynge, Elsebeth; Bonde, Jesper

    2014-01-01

    We aimed to determine the disagreement in primary cervical screening between four human papillomavirus assays: Hybrid Capture 2, cobas, CLART, and APTIMA. Material from 5,064 SurePath samples of women participating in routine cervical screening in Copenhagen, Denmark, was tested with the four assays. Positive agreement between the assays was measured as the conditional probability that the results of all compared assays were positive given that at least one assay returned a positive result. Of all 5,064 samples, 1,679 (33.2%) tested positive on at least one of the assays. Among these, 41% tested positive on all four. Agreement was lower in women aged ≥30 years (30%, vs. 49% at <30 years), in primary screening samples (29%, vs. 38% in follow-up samples), and in women with concurrent normal cytology (22%, vs. 68% with abnormal cytology). Among primary screening samples from women aged 30–65 years (n = 2,881), 23% tested positive on at least one assay, and 42 to 58% of these showed positive agreement on any compared pair of the assays. While 4% of primary screening samples showed abnormal cytology, 6 to 10% were discordant on any pair of assays. A literature review corroborated our findings of considerable disagreement between human papillomavirus assays. This suggested that the extent of disagreement in primary screening is neither population- nor storage media-specific, leaving assay design differences as the most probable cause. The substantially different selection of women testing positive on the various human papillomavirus assays represents an unexpected challenge for the choice of an assay in primary cervical screening, and for follow up of in particular HPV positive/cytology normal women. PMID:24466262

  12. Syzygium cumini inhibits growth and induces apoptosis in cervical cancer cell lines: a primary study.

    PubMed

    Barh, D; Viswanathan, G

    2008-01-01

    Cervical cancer is common among women in the Indian subcontinent and the incidences and death rates are gradually increasing over the years. Several dietary phytochemicals have been reported to have growth inhibitory and apoptotic effect on HeLa and other cervical cell lines. In this study, using Hoechst 33342 staining, MTT, Annexin V-FLUOS/PI and TUNEL assays we demonstrated that Syzygium cumini extract inhibits the growth and induces apoptosis in HeLa and SiHa cervical cancer cell lines in a dose- and time-dependent manner. The phytochemical, its mode of action and safety issues are yet to be determined. PMID:22275971

  13. Primary radiation therapy in the treatment of anal carcinoma

    SciTech Connect

    Cantril, S.T.; Green, J.P.; Schall, G.L.; Schaupp, W.C.

    1983-09-01

    From 1966 to 1981, 47 patients with a diagnosis of anal carcinoma were irradiated. This group was composed of 23 males and 24 females, with age ranging from 38 to 84 years (average 64.4 years). Five patients were treated preoperatively and 34 were treated definitively with cancericidal doses of irradiation. Acute radiation reactions requiring a rest-break were noted in 28% of patients, but all were managed as outpatients without untoward chronic sequelae. Chronic complications were noted in 13 patients, including two patients who required colostomy for severe anal stenosis and two who required A-P resection for large painful ulcers. Twenty-eight of 35 patients (80%) treated with irradiation alone have remained locally controlled without further treatment. An additional four have been salvaged by surgery. Only three patients had interstitial implants as part of their treatment course. Actuarial survival at five years for the N/sub 0/ patients and the group as a whole are 95.6 and 79.3%, respectively. It is concluded that external beam irradiation alone, properly fractionated to cancericidal doses, can control anal carcinoma with acceptable morbidity rates and without the use of either chemotherapy or interstitial implants in most cases. There is also a strong correlation suggesting that anal intercourse and male homosexuality play a significant role in the etiology of this disease.

  14. TP53 gene mutations and protein accumulation in primary vaginal carcinomas.

    PubMed Central

    Skomedal, H.; Kristensen, G.; Helland, A.; Nesland, J. M.; Kooi, S.; Børresen, A. L.; Holm, R.

    1995-01-01

    Primary carcinomas from 46 patients were screened for TP53 alterations. Immunohistochemistry demonstrated nuclear TP53 protein accumulation in 22 (48%) cases using the polyclonal CM1 antiserum, whereas 15 (33%) cases showed positive nuclear staining with the mononuclear antibody PAb 1801. Constant denaturant gel electrophoresis (CDGE) was used to screen 27 of the vaginal carcinomas for mutations in the conserved regions of the TP53 gene (exons 5-8). Six of these tumours (22%) contained mutations: four were found in exon 5 and two in exon 8. A total of 50% of the primary vaginal carcinomas carried a TP53 alteration. These results indicate that TP53 abnormalities may be involved in the development of these tumours. However, there was no significant association between TP53 abnormalities and survival. Images Figure 1 Figure 2 PMID:7599041

  15. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks. PMID:26881596

  16. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks.

  17. [Magnetotherapy designed to affect cervical sympathetic ganglia for the treatment of patients with primary open-angle glaucoma].

    PubMed

    Veselova, E V; Kamenskikh, T G; Raĭgorodkiĭ, Iu M; Kolbenev, I O; Myshkina, E S

    2010-01-01

    The traveling magnetic field was used to treat primary open-angle glaucoma. The field was applied to the projection of cervical sympathetic ganglia of the patients. Hemodynamic parameters of posterior short ciliary arteries and central retinal artery were analysed along with visual evoked potentials, visual field limits, and visual acuity. It was shown that magnetotherapy with the use of an AMO-ATOS apparatus produces better clinical results in patients with stage I and II primary open-angle glaucoma compared with medicamentous therapy (intake of trental tablets). PMID:21328900

  18. External ultrasonography of the neck does not add diagnostic value to integrated positron emission tomography-computed tomography (PET-CT) scanning in the diagnosis of cervical lymph node metastases in patients with esophageal carcinoma.

    PubMed

    Blom, R L G M; Vliegen, R F A; Schreurs, W M J; Belgers, H J; Stohr, I; Oostenbrug, L E; Sosef, M N

    2012-08-01

    One of the objectives of preoperative imaging in esophageal cancer patients is the detection of cervical lymph node metastases. Traditionally, external ultrasonography of the neck has been combined with computed tomography (CT) in order to improve the detection of cervical metastases. In general, integrated positron emission tomography-computed tomography (PET-CT) has been shown to be superior to CT or PET regarding staging and therefore may limit the role of external ultrasonography of the neck. The objective of this study was to determine the additional value of external ultrasonography of the neck to PET-CT. This study included all patients referred our center for treatment of esophageal carcinoma. Diagnostic staging was performed to determine treatment plan. Cervical lymph nodes were evaluated by external ultrasonography of the neck and PET-CT. In case of suspect lymph nodes on external ultrasonography or PET-CT, fine needle aspiration (FNA) was performed. Between 2008 and 2010, 170 out of 195 referred patients underwent both external ultrasonography of the neck and PET-CT. Of all patients, 84% were diagnosed with a tumor at or below the distal esophagus. In 140 of 170 patients, the cervical region was not suspect; no FNA was performed. Seven out of 170 patients had suspect nodes on both PET-CT and external ultrasonography. Five out of seven patients had cytologically confirmed malignant lymph nodes, one of seven had benign nodes, in one patient FNA was not performed; exclusion from esophagectomy was based on intra-abdominal metastases. In one out of 170 patients, PET-CT showed suspect nodes combined with a negative external ultrasonography; cytology of these nodes was benign. Twenty-two out of 170 patients had a negative PET-CT with suspect nodes on external ultrasonography. In 18 of 22 patients, cervical lymph nodes were cytologically confirmed benign; in four patients, FNA was not possible or inconclusive. At a median postoperative follow-up of 15 months

  19. Human papillomavirus testing versus cytology in primary cervical cancer screening: End-of-study and extended follow-up results from the Canadian cervical cancer screening trial.

    PubMed

    Isidean, Sandra D; Mayrand, Marie-Hélène; Ramanakumar, Agnihotram V; Gilbert, Laura; Reid, Stephanie L; Rodrigues, Isabel; Ferenczy, Alex; Ratnam, Sam; Coutlée, François; Franco, Eduardo L

    2016-12-01

    The Canadian Cervical Cancer Screening Trial was a randomized controlled trial comparing the performance of human papillomavirus (HPV) testing and Papanicolaou cytology to detect cervical intraepithelial neoplasia of grades 2 or worse (CIN2+) among women aged 30-69 years attending routine cervical cancer screening in Montreal and St. John's, Canada (n = 10,154). We examined screening and prognostic values of enrollment cytologic and HPV testing results. Extended follow-up data were available for St. John's participants (n = 5,754; 501,682.6 person-months). HPV testing detected more CIN2+ than cytology during protocol-defined (82.9 vs. 44.4%) and extended (54.2 vs. 19.3%) follow-up periods, respectively. Three-year risks ranged from 0.87% (95% CI: 0.37-2.05) for HPV-/Pap- women to 35.77% (95% CI: 25.88-48.04) for HPV+/Pap+ women. Genotype-specific risks ranged from 0.90% (95% CI: 0.40-2.01) to 43.84% (95% CI: 32.42-57.24) among HPV- and HPV16+ women, respectively, exceeding those associated with Pap+ or HPV+ results taken individually or jointly. Ten-year risks ranged from 1.15% (95% CI: 0.60-2.19) for HPV-/Pap- women to 26.05% (95% CI: 15.34-42.13) for HPV+/Pap+ women and genotype-specific risks ranged from 1.13% (95% CI: 0.59-2.14) to 32.78% (95% CI: 21.15-48.51) among women testing HPV- and HPV16+, respectively. Abnormal cytology stratified risks most meaningfully for HPV+ women. Primary HPV testing every 3 years provided a similar or greater level of reassurance against disease risks as currently recommended screening strategies. HPV-based cervical screening may allow for greater disease detection than cytology-based screening and permit safe extensions of screening intervals; genotype-specific testing could provide further improvement in the positive predictive value of such screening. PMID:27538188

  20. Alterations in exon 1 of c-myc and expression of p62c-myc in cervical squamous cell carcinoma.

    PubMed Central

    O'Leary, J J; Landers, R J; Crowley, M; Healy, I; Kealy, W F; Hogan, J; Doyle, C T

    1997-01-01

    AIMS: To examine human papillomavirus (HPV) positive and negative squamous cell carcinomas of the cervix for structural alterations in exon 1 c-myc; and to investigate the expression pattern of p62, the protein product of c-myc. MATERIAL: Archival paraffin wax embedded tissues of cervical squamous cell carcinomas, stage I and II, retrieved from the files of the department of pathology, University College Cork, Ireland: 40 cases were examined for alterations in exon 1 of c-myc; 57 cases were used for immunocytochemical p62 analysis. METHODS: c-myc exon 1 PCR on HPV positive and negative stage I and II cervical squamous cell carcinomas was performed using primers designed to fragile sites in exon 1 of the c-myc oncogene, which are frequently involved in translocation phenomena and deletions in other neoplasms. This region is bordered by two promoter sequences P1 and P2. In addition, the expression of p62 was evaluated using the monoclonal antibody Mycl-9E10. RESULTS: Alterations in exon 1 of c-myc were shown in 7.5% of squamous cell carcinomas of the cervix. Changes in exon 1 and 2 of c-myc were also found in COLO 320 cells and Raji cells. These alterations were due to small deletions within exon 1 of c-myc, but point polymorphisms occurring within the priming sites (in one case) may also have occurred. The alterations uncovered appeared "clonal," as replicate samples showed the same amplicon band pattern. Expression of c-myc was variable, with cytoplasmic staining patterns predominating. All cases which showed exon 1 alterations were HPV positive and had strong nuclear positivity on p62 immunocytochemistry. CONCLUSIONS: Alterations in exon 1 of c-myc occur in a minority of cervical cancers and there was increased expression of p62 in a cohort of HPV positive and negative cervical squamous cell carcinomas. Exon 1 alterations may provide an alternative route to c-myc activation in early squamous cell carcinoma. Images PMID:9462237

  1. Burden of hospital admissions for cervical cancer in Spain during 1999-2002.

    PubMed

    Gil, Angel; San-Martín, María; Gil, Ruth; Hernández, Valentín; Ribes, Josepa; González, Antonio

    2007-01-01

    Population-based retrospective epidemiological study to estimate the burden of to hospitalizations by cervical cancer in Spain. It was conducted by using hospital discharge data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos (CMBD). Records of all patients admitted to hospital with a diagnosis of malignant neoplasm of the cervix (ICD-9-MC codes 180.0-180.9) or carcinoma in situ of cervix (code 233.1) during a four year period (1999-2002), were selected. An annual average of 4,151 hospitalizations with a primary or secondary diagnosis of cervical cancer and 2,761 hospitalizations due to carcinoma in situ were identified. Annually there were 25.5 and 17.0 hospitalizations by cervical cancer and carcinoma in situ per 100,000 women > or =20 years of age, respectively. Hospitalization rate by cervical cancer and carcinoma in situ peaks in between 45 and 59 years of age (39.4 admissions per 100,000 women) and 30 to 44 years of age (32.2 per 100,000 women), respectively. The mean cost of a hospitalization by cervical cancer and carcinoma in situ euro3,098 and euro2,192, respectively. The estimated annual cost of hospitalizations cervical cancer and carcinoma in situ in Spain was 19 million euro.

  2. Evaluation and management of head and neck squamous cell carcinoma of unknown primary.

    PubMed

    Martin, Jeffrey M; Galloway, Thomas J

    2015-07-01

    The diagnostic evaluation and therapeutic management of a patient with squamous cell carcinoma of an unknown primary (SCCUP) has considerably evolved over recent decades and will likely continue to change as a result of the improving ability to identify small primary tumors and better tailor the implementation of multimodality therapy. By application of the general principles of head and neck oncology, physicians and surgeons are often able to achieve satisfactory control of the disease in patients with SCCUP.

  3. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    PubMed

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology.

  4. Intrameningioma Metastasis: Clinical Manifestation of Occult Primary Lung Carcinoma.

    PubMed

    Nadeem, Muhammad; Assad, Salman; Nasir, Humaira; Mansoor, Salman; Khan, Innayatullah; Manzoor, Hana; Kiani, Immad; Raja, Avais; Sulehria, Touqeer

    2016-01-01

    We report a case of lung carcinoma metastasizing into a meningioma in a 68-year-old female, who presented with progressively worsening right-sided hemiparesis and multiple episodes of adult onset epilepsy. Magnetic resonance imaging revealed an oval-shaped extra-axial hypointense lesion with a central hyperintense nodule in the left frontal region favoring a most probable diagnosis of a meningioma. Left frontoparietal craniotomy and excision of the tumor were carried out and histopathology with hematoxylin and eosin stain revealed a meningioma with metastatic adenocarcinoma and was confirmed by immunohistochemistry. The origin of metastasis was presumed to be from the lungs. A computed tomography (CT) scan of the chest with contrast showed a 3.1 x 2.9 cm mass with spiculated margins in the left lower lobe. Fine needle aspiration cytology (FNAC) proved it to be adenocarcinoma. PMID:27588225

  5. Intrameningioma Metastasis: Clinical Manifestation of Occult Primary Lung Carcinoma

    PubMed Central

    Nadeem, Muhammad; Nasir, Humaira; Mansoor, Salman; Khan, Innayatullah; Manzoor, Hana; Kiani, Immad; Raja, Avais; Sulehria, Touqeer

    2016-01-01

    We report a case of lung carcinoma metastasizing into a meningioma in a 68-year-old female, who presented with progressively worsening right-sided hemiparesis and multiple episodes of adult onset epilepsy. Magnetic resonance imaging revealed an oval-shaped extra-axial hypointense lesion with a central hyperintense nodule in the left frontal region favoring a most probable diagnosis of a meningioma. Left frontoparietal craniotomy and excision of the tumor were carried out and histopathology with hematoxylin and eosin stain revealed a meningioma with metastatic adenocarcinoma and was confirmed by immunohistochemistry. The origin of metastasis was presumed to be from the lungs. A computed tomography (CT) scan of the chest with contrast showed a 3.1 x 2.9 cm mass with spiculated margins in the left lower lobe. Fine needle aspiration cytology (FNAC) proved it to be adenocarcinoma. PMID:27588225

  6. Primary colonic signet ring cell carcinoma in a young patient.

    PubMed

    Prabhu, Raghunath; Kumar, Neha; Krishna, Sunil; Shenoy, Rajgopal

    2014-01-01

    A 28-year-old woman presented with colicky abdominal pain for 3 months. Pain was associated with episodes of vomiting, abdominal distension and constipation. She also had loss of weight for this duration. General physical examination was unremarkable and the abdomen was soft, with no palpable organomegaly. A CT of the abdomen showed small bowel and ascending colon dilation with multiple air fluid levels. There was also a short segment of circumferential bowel wall thickening and luminal narrowing in the hepatic flexure with sudden transition of bowel diameter. She underwent a right hemicolectomy after necessary preoperative investigations. Histopathology revealed signet ring cell carcinoma (SRCC). This case highlights the importance of detecting such a lesion in a young, otherwise fit woman. The challenge lies in early diagnosis and awareness of general practitioners about this aggressive form of colonic tumours. PMID:24654235

  7. Cytochalasin B induces apoptosis through the mitochondrial apoptotic pathway in HeLa human cervical carcinoma cells.

    PubMed

    Hwang, Jiyoung; Yi, Myeongjin; Zhang, Xin; Xu, Yi; Jung, Jee H; Kim, Dong-Kyoo

    2013-10-01

    Cytochalasin B (CB) is a cell-permeable mycotoxin. It inhibits cytoplasmic division by blocking the formation of contractile microfilaments, it inhibits cell movement and induces nuclear extrusion. In the present study, we investigated the anticancer activity of CB in HeLa human cervical carcinoma cells. CB showed significant cytotoxicity, with an IC50 of 7.9 µM, in a WST-8 assay and significantly inhibited cell proliferation. Furthermore, results from Annexin V-FITC/propidium iodide double-staining indicated that CB induced early apoptosis of HeLa cells in a time-dependent manner. The cells exhibited apoptotic morphology, including cell shrinkage and nuclear condensation. CB induced cell cycle arrest at the S phase. We also observed inhibition of DNA replication in a [3H]-thymidine incorporation assay. Furthermore, CB induced a time-dependent increase in reactive oxygen species and a decrease in mitochondrial membrane potential. Western blot analysis showed an increase in levels of mitochondrial factors Bax and Bcl-2, which was followed by activation of caspase-9 and -3. These results suggested that CB induced apoptosis via a mitochondrial-dependent pathway in HeLa cells. PMID:23863920

  8. Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above.

    PubMed

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah; Ejegod, Ditte; Rygaard, Carsten; Lynge, Elsebeth

    2016-01-01

    In women aged ≥ 30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30-65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥ CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥ CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥ CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥ 50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30-65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing. PMID:26789267

  9. Primary multiple clear cell variant urothelial carcinomas of urinary bladder: a rare case report

    PubMed Central

    Zhang, Yutao; Huang, Jun; Feng, Hao; Tang, Yun

    2014-01-01

    Clear cell variant urothelial carcinoma of urinary bladder was very rare. There were only 6 report articles included by Pubmed and total 8 cases had been described till now. All of the past reports described single tumor of urinary bladder, but multiple carcinomas had not been reported. Here we reported a 65-years-old Chinese man who complained of intermittent gross hematuria and odynuria for more than 2 months in January 2013. Only one cauliflower-like tumor was detected approximately in the left wall of the urinary bladder with cystoscopy and the biopsy specimen was diagnosed as “urothelial carcinoma, high grade”. However, three tumors were found in anterior wall (×2) near neck of urinary bladder and posterior wall (×1) of the urinary bladder during transurethral resection of the bladder tumor. Typical urothelial carcinoma with partial clear cell appearance made it difficult to make a precise pathological diagnosis and immunohistochemical stain helped to diagnose the case as clear cell variant urothelial carcinoma, but not metastasis of the renal cell carcinoma. Finally, computerized tomographic scanning confirmed that there was no primary tumor in the kidney. The clinical and pathological characteristic had not been identified for the limited reports. More work should be done to know this kind of tumor well for guiding clinical therapy. PMID:25031765

  10. The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas.

    PubMed

    El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; Abdelmeged, Ayman; Rahman, Mohamed Fathy Abdel; Moustafa, Alaa A E

    2016-03-01

    Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for differentiating lung adenocarcinoma from squamous cell carcinoma and also for differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair-boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic carcinomas and help to determine the primary sites of metastatic carcinomas. Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively. While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %, respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of papillary carcinoma respectively, and both were positive in 100 % of follicular carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8 were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 % of chromophobe carcinoma respectively. TTF-1 was negative in all renal carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of serous mucinous carcinomas, respectively. It was also positive in 100 % of endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF-1, and PAX8 may help in differentiating between primary lung adenocarcinoma and metastatic lung carcinomas.

  11. A Dosimetric Study of Using Fixed-Jaw Volumetric Modulated Arc Therapy for the Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastasis

    PubMed Central

    Chen, Jian-Zhou; Zhai, Tian-Tian; Huang, Bao-Tian; Li, De-Rui; Chen, Chuang-Zhen

    2016-01-01

    Purpose To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT) and large-field volumetric modulated radiotherapy (LF-VMAT) for nasopharyngeal carcinoma (NPC) with cervical lymph node metastasis. Methods Computed tomography (CT) datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV) coverage, conformity index (CI), homogeneity index (HI), organ-at-risk sparing, monitor units (MUs) and treatment time (TT). Results The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes), PTV1 (high-risk PTV) and PTV2 (low-risk PTV) than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor). The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR) volumes (PRVs) of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87) were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62). In terms of the TT, no significant difference was found between the two kinds of plans. Conclusions FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs. PMID:27231871

  12. Influence of chromosomal integration on glucocorticoid-regulated transcription of growth-stimulating papillomavirus genes E6 and E7 in cervical carcinoma cells

    SciTech Connect

    Von Knebel Doeberitz, M.; Bauknecht, T.; Bartsch, D.; Zur Hausen, H. )

    1991-02-15

    In most cervical carcinoma cells the E6 and E7 genes of specific human papillomaviruses are transcribed from viral sequences integrated into host cell chromosomes. Glucocorticoids activate the promoter elements of various human papillomaviruses in transient-expression assays. The authors have analyzed the effect of dexamethasone on the transcription rate of human papillomaviruses 18 E6 and E7 genes integrated at different chromosomal sites in four cervical cancer cell lines. Dexamethasone led to an increase in the transcription rate of the integrated E6-E7 sequences in C4-1 and C4-2 cells but led to a decrease in SW 756 cells and did not affect the transcription rate in HeLa cells. It thus appears that dominant regulatory mechanisms presumably depending on the chromosomal integration site are able to override the response of the viral promoter to steroid hormones. The growth rate of all dexamethasone-treated cell lines correlated consistently with the expression of the papillomavirus E6 and E7 genes, supporting their role in the maintenance of the proliferative phenotype of cervical carcinoma cells. Since human papillomaviruses are integrated into the host cell genome at variable, presumably randomly selected chromosomal loci, regulatory mechanisms that influence viral gene expression, and hence cell growth, may differ among cancers of independent clonal origin.

  13. Anterior Urethrectomy for Primary Carcinoma of the Female Urethra Mimicking a Urethral Caruncle

    PubMed Central

    Shim, Ji Sung; Oh, Mi Mi; Lee, Jeong Gu

    2013-01-01

    Here we report a case of primary carcinoma of the female urethra. A 52-year-old woman presented with a palpable urethral mass associated with intermittent pain that she first experienced a few months prior. Clinical examination showed a urethral mass that appeared to be a caruncle; therefore, simple carunclectomy was performed. However, on histological examination, the mass was revealed to be a squamous cell carcinoma; therefore, anterior urethrectomy was performed. During a 4-year follow-up period, the patient has been well with no dysuria, dyspareunia, or incontinence. PMID:24466468

  14. Effect of embolic microspheres in the treatment of primary hepatic carcinoma.

    PubMed

    Wang, K B; Sui, H; Li, W; Cui, L M; Bai, B

    2016-01-01

    The purpose of this study was to evaluate the clinical effect of embolic microspheres in the treatment of primary hepatic carcinoma. Fifty-eight patients who were confirmed with primary hepatic carcinoma by imaging were retrospectively analyzed. They were firstly perfused with 50 mg of oxaliplatin and 40 mg of epirubicin. Embolic microspheres were then injected into the distal end of targeted blood vessels. After this procedure, dynamic observation was carried out until tumor stain disappeared. Liver function and blood indexes were reexamined on days 5, 6, 7 and 28 after treatment, and moreover, the liver was examined with Magnetic Resonance Imaging (MRI) or computed tomography (CT). Compared to traditional lipiodol embolization, embolic microspheres did not aggregate the damage on liver function and the imaging examination suggested necrosis of some tumor tissues. Embolic microspheres proved to be effective in treating primary hepatic carcinoma. It produces no damage on liver function and can lead to significant shrinkage of hepatic carcinoma and necrosis of some tumor tissues. Embolic microspheres, which merely block distal branches of tumor-feeding artery, can avoid collateral circulation induced by permanent blocking, thus achieve a good treatment effect.

  15. Primary carcinoma of the gallbladder. Adjuvant postoperative external irradiation

    SciTech Connect

    Bosset, J.F.; Mantion, G.; Gillet, M.; Pelissier, E.; Boulenger, M.; Maingon, P.; Corbion, O.; Schraub, S. )

    1989-11-01

    Seven patients received the same postoperative (Postop) external-beam irradiation (NRT) after apparent complete removal of gallbladder carcinoma between August 1983 to February 1988. A dosage of 4600 cGy were delivered on a first volume (average treated volume 0.87 liters) corresponding to this of potentially locoregional disease, completed by a boost dose of 900 cGy on the gallbladder bed. Moderate acute side effects were seen in five patients; regressive dyspepsia in three and mean weight loss of 1.5 kg in three. The minimum follow-up is 5 months and the maximum is 58 months. Five patients are alive with no evidence of disease (NED) after 5, 9, 11, 31, and 58 months, respectively. One died at 12 months with local recurrence, liver metastasis, and peritoneal implants. Another one died at 26 months of abdominal recurrence. With regard to the natural history of this tumor, the dismal results obtained by surgery alone, and our preliminary data, we advocate Postop adjuvant XRT as a safe treatment.

  16. Invasive Stratified Mucin-producing Carcinoma and Stratified Mucin-producing Intraepithelial Lesion (SMILE): 15 Cases Presenting a Spectrum of Cervical Neoplasia With Description of a Distinctive Variant of Invasive Adenocarcinoma.

    PubMed

    Lastra, Ricardo R; Park, Kay J; Schoolmeester, J Kenneth

    2016-02-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is a cervical intraepithelial lesion, distinct from conventional squamous or glandular counterparts, believed to arise from embryonic cells at the transformation zone by transdifferentiation during high-risk HPV-associated carcinogenesis. It is characterized by stratified, immature epithelial cells displaying varying quantities of intracytoplasmic mucin throughout the majority of the lesional epithelium. We identified a distinct form of invasive cervical carcinoma with morphologic features identical to those in SMILE, which we have termed "invasive stratified mucin-producing carcinoma." Fifteen cases from 15 patients (mean 36 y; range, 22 to 64 y) were retrieved from the pathology archives of multiple institutions with a diagnosis of either SMILE or invasive cervical carcinoma with a description or comment about the invasive tumor's resemblance to SMILE. Seven cases had solely intraepithelial disease with a component of SMILE (mean 29 y; range, 22 to 40 y). The 8 other cases had invasive stratified mucin-producing carcinoma (mean 44; range, 34 to 64 y) in which SMILE was identified in 7. All cases of invasive stratified mucin-producing carcinoma demonstrated stratified, immature nuclei with intracytoplasmic mucin, which morphologically varied between cases from "mucin-rich" to "mucin-poor" in a similar manner to SMILE. All cases had mitotic figures and apoptotic debris, and an intralesional neutrophilic infiltrate was seen in the majority of cases. In cases of invasive carcinoma, the depth of invasion ranged from <1 to 19 mm. Follow-up information was available in 8 cases and ranged from 1 to 36 months (mean 11 mo). Three cases of invasive stratified mucin-producing carcinoma had biopsy or resection-proven metastatic carcinoma on follow-up. These 15 cases of cervical stratified mucin-producing lesions show a combination of intraepithelial and invasive growth patterns. Given that SMILE is well rooted as a

  17. Human papilloma virus early proteins E6 (HPV16/18-E6) and the cell cycle marker P16 (INK4a) are useful prognostic markers in uterine cervical carcinomas in Qassim Region--Saudi Arabia.

    PubMed

    Omran, O M; AlSheeha, M

    2015-01-01

    Cervical cancer is a common and an important public health problem for adult women in developing countries. In contrast, cervical cancer incidence is low in Saudi Arabia. High-risk types of human papilloma viruses (HPV16 and HPV18) are the most significant risk factors for cervical cancer. HPV16/18-E6 oncoprotein is associated with HPV etiology, viral persistence and epithelial transformation. Cell cycle protein p16 INK4a (p16) plays an important role in the pathophysiology of cervical carcinomas. The aims of this study were to investigate the expression of HPV16/18-E6 and p16 in uterine cervical carcinomas in Qassim Region--Saudi Arabia, and to relate the results to the established clinicopathological prognostic parameters (age of the patient, educational level, birth control methods, number of pregnancy, smoking status, degree of histological differentiation, clinical stage, and lymph node metastasis) The study included 40 specimens of uterine cervical squamous cell carcinomas diagnosed and confirmed by biopsy. Histopathological classification of cervical tumors cases was performed according to the International Federation of Gynecology and Obstetrics (FIGO). Immunohistochemical analysis for HPV16/18-E6 and p16 were carried out on formalin-fixed paraffin-embedded sections of cervical tissues using avidin-biotin peroxidase method. There was a significant statistical correlation between HPV16/18-E6 expression in cervical carcinoma and nationality, smoking status and size of the tumor. HPV16/18-E6 oncoprotein expression in normal lymphocytes and endothelial cells in the tumor tissues and the adjacent normal cervical tissues suggest the possibility that HPV infection might spread to other organs through blood circulation. P16 expression has been correlated with high grade, stage of cervical SCC and HPV16/18-E6 expression. The current study supports the critical function of p16 and HPV16/18-E6 as specific markers for cervical carcinoma. However the potential for usage

  18. [Preoperative endocavitary curietherapy of stage Ib-IIa-IIb cervical carcinoma. Personal observations].

    PubMed

    Gabriele, A M; Boidi Trotti, A; Fracchia, F; Rosmino, C; Rovea, P; Tardy, A

    1989-05-01

    From 1980 through 1984, 41 patients with squamous cell cervix carcinoma and 1 with adenosquamous carcinoma were treated with preoperative irradiation. Clinical stages were Ib in 6 patients, IIa in 24, and IIb in 12. At surgery, lymph node metastases were found in 5 cases, and residual tumors in 8. The latter risk patients were given further external radiotherapy after surgery. Overall three-year survival rates for FIGO stage Ib was 100%; 91.6% for stage IIa, and 83% for stage IIb (minimum follow-up: 3 years). Two patients died from locoregional recurrence of the disease 12-24 months after the treatment, and 2 from distant metastases; 5 patients have showed signs of local improvement. Our results seem to point to pelvic lymph node involvement as the major prognostic factor: in fact, 40% only of the patients with involved lymph nodes is alive. Actuarial survival rates show 90.4% of patients to be alive at 5 years. Tolerance to the combined use radiotherapy and surgery was fair: no severe side-effects were observed. Even though our results are encouraging, a randomized study is still recommended to verify the actual value of this treatment versus combined surgery and radiotherapy or radiotherapy alone.

  19. [Hypopharyngeal carcinoma and red ear drum].

    PubMed

    Bender, B; Widmann, G; Riechelmann, H; Schmutzhard, J

    2011-04-01

    A 46-year-old male patient with an unresectable hypopharyngeal carcinoma was treated with primary radio-chemotherapy. At follow-up, the patient presented with a red ear drum and combined hearing loss. Because of radiotherapy-induced tubal dysfunction, paracentesis was performed. Biopsy of the polypoid middle ear mucosa revealed petrous bone infiltration of hypopharyngeal carcinoma. MRI studies revealed paracarotideal tumor infiltration to the petrous bone and the middle ear arising from a cervical retropharyngeal lymph node metastasis. PMID:20963385

  20. Rigosertib Is a More Effective Radiosensitizer Than Cisplatin in Concurrent Chemoradiation Treatment of Cervical Carcinoma, In Vitro and In Vivo

    SciTech Connect

    Agoni, Lorenzo; Basu, Indranil; Gupta, Seema; Alfieri, Alan; Gambino, Angela; Goldberg, Gary L.; Reddy, E. Premkumar; Guha, Chandan

    2014-04-01

    Purpose: To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies. Methods and Materials: Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts. Results: Rigosertib was demonstrated to induce a G{sub 2}/M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay. Conclusions: Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma.

  1. Molecular detection and genotyping of human papillomavirus in cervical carcinoma biopsies in an area of high incidence of cancer from Moroccan women.

    PubMed

    Khair, M Meftah El; Mzibri, M El; Mhand, R Ait; Benider, A; Benchekroun, N; Fahime, E M El; Benchekroun, M N; Ennaji, M M

    2009-04-01

    Cervical cancer is a leading cause of cancer-related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Eighty nine cervical carcinoma biopsies collected from women visiting the Oncologic Center in Casablanca (Centre Hospitalier Universitaire Ibn Rochd, Morocco) for cervical cancer symptoms, were screened for HPV DNA by polymerase chain reaction amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 45, and 59. Using very high stringency hybridization the HPV types could be easily distinguished. After preliminary clinical sorting, 92% (82/89) of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent 36.6% (30/82) of the positive samples, followed by HPV 18; 19.5% (16/82). Double or even multiple infections by the different HPV types were also detected (35.5% of the positive samples); dual infections were the more frequent, with the following combinations of HPVs: HPV16/HPV18 (21% of the positives samples) and HPV16/HPV45 (8.5%).

  2. [Mediastinal lymph node carcinoma of unknown primary site; report of a case].

    PubMed

    Miura, K; Yoshizawa, K; Tamaki, M; Okumura, K; Furukita, Y

    2009-03-01

    A 44-year-old woman was admitted to our hospital because of mediastinal mass. Serum levels of carcinoembryonic antigen (CEA) were found to be elevated. No preoperative examination could detect the primary lesion. The tumor was resected through right thoracotomy. Histological examination revealed poorly differentiated adenocarcinoma. She was diagonosed as metastatic mediastinal lymph node carcinoma of unknown primary site. She received radiotherapy and chemotherapy and is desease free 29 months after operation. Good results may be obtained by multimodality therapies for cancer in mediastinal lymph node of unknown primary site. PMID:19280962

  3. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

    PubMed

    Masai, Kyohei; Tsuta, Koji; Kawago, Mitsumasa; Tatsumori, Takahiro; Kinno, Tomoaki; Taniyama, Tomoko; Yoshida, Akihiko; Asamura, Hisao; Tsuda, Hitoshi

    2013-07-01

    Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

  4. Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient

    PubMed Central

    Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

    2016-01-01

    Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis. PMID:27721883

  5. Margins for cervical and vulvar cancer.

    PubMed

    Khanna, Namita; Rauh, Lisa A; Lachiewicz, Mark P; Horowitz, Ira R

    2016-03-01

    Surgery is the primary treatment for vulvar cancer as well as early-stage carcinoma of the cervix. This article reviews the significance of margin status after surgery on overall survival, need for further surgical intervention, and role for possible adjuvant therapy. It summarizes the abundant literature on margin status in vulvar cancer and highlights the need for further investigation on the prognostic significance of margins in cervical cancer. In addition, it reviews other important operative considerations.

  6. [Membrane type 1 matrix metalloproteinase (MT1-MMP) and the regulators of its activity as invasive factors in squamous cell cervical carcinomas].

    PubMed

    Timoshenko, O S; Gureeva, T A; Kugaevskaia, E V; Solov'eva, N I

    2014-01-01

    Membrane type 1 matrix metalloproteinase (MT1MMP) is one of matrix metalloproteinases (MMP), which play а key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of MT1MMP and endogenous regulators of its activity: the activator - furin and the inhibitor - TIMP-2, as invasive factors of squamous cell cervical carcinomas (SCC). The study was carried out using 11 specimens of SCC and 11 specimens of morphologically normal tissue adjacent to the tumor. It was shown that the increase of MT1-MMP and furin expression and low of TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. Moreover, substantial expression of MT1-MMP was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of the cervical tumor.

  7. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2016-11-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Vaginal Cancer

  8. Visual Inspection after Acetic Acid (VIA) Is Highly Heterogeneous in Primary Cervical Screening in Amazonian Peru

    PubMed Central

    Almonte, Maribel; Ferreccio, Catterina; Luciani, Silvana; Gonzales, Miguel; Delgado, Jose M.; Santos, Carlos; Alvarez, Manuel; Cuzick, Jack; Sasieni, Peter

    2015-01-01

    Background Conventional cytology (Pap) and visual inspection after the application of acetic acid (VIA) are currently used in primary screening in Peru. Studies suggest that the quality of VIA is highly variable. Over 36 000 women were screened with Pap and VIA in the TATI (Tamizaje y Tratamiento Inmediato de Lesiones Cervico-uterinas) project conducted in Amazonian Peru. Within a nested study to compare several screening techniques (C-TATI), a total of 5435 women were additionally screened with liquid-based cytology (LBC) and high-risk human papillomavirus testing (HR-HPV). We investigate the variation of positivity rates of VIA, Pap, LBC and HR-HPV in C-TATI and of VIA in the full TATI intervention. Methods At the screening visit, midwives collected three cervical samples for Pap, LBC and HC2 before performing VIA. The dispersion factor “D” (D = Pearson chi-square value/degrees-of-freedom) was used to measure the variability of tests results. Within C-TATI, the variability of positivity rates of VIA, Pap, LBC and HR-HPV was also graphically assessed with box- and scatter plots by midwife and month of screening. Funnel plots and smoothed scatter plots were used to correlate the variation of VIA by the number of examinations performed by each midwife over the full TATI intervention. Results Consistently over TATI, VIA results were highly variable, independently of the examiner, the time when the test was performed and the number of tests the examiner performed (D>6, p-values<0.001). In C-TATI, VIA results varied the most while those of HR-HPV varied the least (Ds>25, p-values<0.001 for VIA, Ds<1.6, p-values>0.05 for HR-HPV). No evidence for correlation between the number of VIAs done per midwife and the variability of VIA results was observed. Conclusion The lack of over-dispersion for HR-HPV detection suggests that the variable VIA results do not reflect true variation in underlying disease, but a lack of consistency in human judgement. PMID:25635965

  9. Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

    PubMed Central

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah; Ejegod, Ditte; Rygaard, Carsten; Lynge, Elsebeth

    2016-01-01

    In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing. PMID:26789267

  10. A colorectal carcinoma imitating a primary ovarian carcinoma in a postpartum woman

    PubMed Central

    Aiyer, Rohit; Sweetman, Kieran; Larsen-Disney, Peter; Fish, Andrew

    2013-01-01

    This is a case report of a 33-year-old woman who presented 5 days post-partum with abdominal distension, abdominal discomfort, increased bladder pressure and fatigue. These symptoms prompted a pelvic ultrasound and CT scan of the chest, abdomen and pelvis which showed a large 20 cm left-sided adnexal mass. Following this imaging, blood tests revealed elevated tumour markers CA-125 and lactate dehydrogenase, resulting in referral to and surgical intervention by the gynaecology oncology team. Pathology and immunohistochemistry indicated that the tumour was a metastasis from the colon, that prompted for colonoscopy which confirmed that the carcinoma was a metastases from the sigmoid. PMID:24275334

  11. Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.

    PubMed

    Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

    1999-01-01

    Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.

  12. Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

    PubMed Central

    Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

    1999-01-01

    Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. α2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because α2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35–60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2–IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented α2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and α2-macroglobulin (r = 0.75, P< 0.01, r = 0.78, P< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in α2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. © 1999 Cancer Research Campaign PMID:9888464

  13. Comparison of the Radiosensitizing Effect of ATR, ATM and DNA-PK Kinase Inhibitors on Cervical Carcinoma Cells.

    PubMed

    Vávrová, J; Zárybnická, L; Jošt, P; Tichý, A; Řezáčová, M; Šinkorová, Z; Pejchal, J

    2016-01-01

    Here, we compared the effects of inhibitors of three phosphatidylinositol-3-kinase-related kinases, ATM, ATR a DNA-PK, on radiosensitization of cervical carcinoma cells. We demonstrated that DNA-PK inhibitor NU7441 enhanced phosphorylation of Chk1 and Chk2 kinases 2 h after irradiation of HeLa cells at a dose of 8 Gy in contrast to ATM kinase inhibitor KU55933, which completely blocked the Chk2 kinase phosphorylation on threonine 68, and ATR kinase inhibitor VE-821, which blocked the Chk1 kinase phosphorylation on serine 345. Most HeLa cells were accumulated in G2 phase of the cell cycle 24 h after irradiation at a high dose of 15 Gy, which was even potentiated after adding the inhibitors NU7441 and KU55933. Compared to all other irradiated groups, inhibitor VE-821 increased the number of cells in S phase and reduced the number of cells in G2 phase 24 h after irradiation at the high dose of 15 Gy. HeLa cells entered the mitotic cycle with unrepaired DNA, which resulted in cell death and the radiosensitizing effect of VE-821. Short-term application of the inhibitors (2 h before and 30 min after the irradiation by the dose of 8 Gy) significantly decreased the colony-forming ability of HeLa cells. Using real-time monitoring of cell proliferation by the xCELLigence system we demonstrated that while the radiosensitizing effect of VE-821 (ATR inhibitor) is manifested early after the irradiation, the radiosensitizing effect of KU55933 (ATM inhibitor) and NU7441 (DNA-PK inhibitor) is only observed as late as 72 h after the irradiation. PMID:27643582

  14. Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

    SciTech Connect

    Klopp, Ann H.; Jhingran, Anuja Ramdas, Latha; Story, Michael D.; Broadus, Russell R.; Lu, Karen H.; Eifel, Patricia J.; Buchholz, Thomas A.

    2008-05-01

    Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified that were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.

  15. Sequence duplication and internal deletion in the integrated human papillomavirus type 16 genome cloned from a cervical carcinoma

    SciTech Connect

    Choo, Kongbung; Lee, Hsienhsiung; Pan, Chaochih; Wu, Sheuemei; Liew, Lipnyin; Cheung, Wingfai; Han, Shouhwa )

    1988-05-01

    Integrated human papillomavirus type 16 (HPV16) sequences were cloned from a cervical carcinoma and analyzed by restriction mapping and nucleotide sequencing. The viral integration sites were mapped within the E1 and E2 open reading frames (ORFs). The E4 and E5 ORFs were entirely deleted. An internal deletion of 376 base pairs (bp) was found disrupting the L1 and L2 ORFs. Sequencing analysis showed that an AGATGT/ACATCT inverted repeat marked the deletion junction with two flanking direct repeats 14 and 8 bp in length. A 1,330-bp sequence duplication containing the long control region (LCR) and the E6 and E7 ORFs was also found. The duplication junction was formed by two 24-bp direct repeats with 79% (19 of 24) homology located within the LCR and the E2 ORF of the prototype viral genome, respectively. This observation leads us to propose that the initial viral integration involved an HPV16 dimer in which the direct repeats in tandem units recombined, resulting in reiteration of only a portion of the original duplication. A guanosine insertion between nucleotides 1,137 and 1,138 created a continuous E1 ORF which was previously shown to be disrupted. Results from this study indicate that sequence reiteration and internal deletion in the integrated, and possibly in the episomal, HPV16 genome are influenced by specific nucleotide sequences in the viral genome. Moreover, reiteration of the LCR/E6/E7 sequences further supports the hypothesis that the E6/E7 ORFs may code for oncogenic proteins and that regulatory signals in the LCR may play a role in cellular transformation.

  16. Interleukin 1 alpha and tumor necrosis factor alpha stimulate autocrine amphiregulin expression and proliferation of human papillomavirus-immortalized and carcinoma-derived cervical epithelial cells.

    PubMed Central

    Woodworth, C D; McMullin, E; Iglesias, M; Plowman, G D

    1995-01-01

    Infection with multiple sexually transmitted agents has been associated with inflammation of the cervix and an increased risk of cervical cancer in women infected with human papillomaviruses (HPVs). Two proinflammatory cytokines, interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha), inhibited proliferation of normal epithelial cells cultured from human cervix. In contrast, both cytokines significantly stimulated proliferation of cervical cell lines (5 of 7) immortalized by transfection with HPV-16 or -18 DNAs or lines derived from cervical carcinomas (7 of 11). Stimulation was dose dependent from 0.01 to 1.0 nM and was blocked by specific inhibitors, such as the IL-1 receptor antagonist or the TNF type 1 or 2 soluble receptors. Growth stimulation by IL-1 alpha or TNF-alpha was accompanied by a 6- to 10-fold increase in RNA encoding amphiregulin, an epidermal growth factor (EGF) receptor ligand. Recombinant human amphiregulin (0.1 nM) was as effective as IL-1 alpha or TNF-alpha in promoting proliferation. Monoclonal antibodies that blocked signal transduction by the EGF receptor or that neutralized amphiregulin activity prevented mitogenic stimulation by IL-1 alpha or TNF-alpha. These studies indicate that IL-1 alpha and TNF-alpha stimulate proliferation of immortal and malignant cervical epithelial cells by an EGF receptor-dependent pathway requiring autocrine stimulation by amphiregulin. Furthermore, they suggest that chronic inflammation and release of proinflammatory cytokines might provide a selective growth advantage for abnormal cervical cells in vivo. Images Fig. 1 Fig. 4 PMID:7708734

  17. Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog

    PubMed Central

    Vieson, Miranda D.; Ramos-Vara, José A.; Moon-Larson, Martha; Saunders, Geoffrey

    2014-01-01

    This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized entity, it may be difficult to distinguish this mass from other thyroid neoplasms, necessitating immunohistochemical characterization. PMID:24690600

  18. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  19. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  20. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  1. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  2. Primary muco-epidermoid carcinoma arising in a parotid lymph node.

    PubMed

    Adkins, G F; Hinckley, D M

    1989-05-01

    A case of well-differentiated muco-epidermoid carcinoma in a parotid lymph node is described. This tumour apparently arose within and was confined to the lymph node. Salivary ductal and acinar inclusions are often found in parotid lymph nodes and these may occasionally give rise to salivary gland tumours, both benign and malignant. The finding of a malignant salivary gland tumour within such a site does not necessarily imply a metastasis from a primary neoplasm elsewhere in the parotid gland.

  3. Helical Tomotherapy Versus Conventional Intensity-Modulated Radiation Therapy for Primary Chemoradiation in Cervical Cancer Patients: An Intraindividual Comparison

    SciTech Connect

    Marnitz, Simone; Lukarski, Dusko; Koehler, Christhardt; Wlodarczyk, Waldemar; Ebert, Andreas; Budach, Volker; Schneider, Achim; Stromberger, Carmen

    2011-10-01

    Purpose: To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. Methods and Materials: Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiation (PEL) and 10 extended-field irradiation (EXT). For treatment planning, the simultaneously integrated boost (SIB) concept was applied. Tumor, pelvic, with or without para-aortic lymph nodes were defined as planning target volume A (PTV-A) with a prescribed dose of 1.8/50.4 Gy (28 fractions). The SIB dose for the parametrium (PTV-B), was 2.12/59.36 Gy. The lower target constraints were 95% of the prescribed dose in 95% of the target volume, and the upper dose constraint was 107%. The irradiated small-bowel volumes were kept as low as possible. For every HT plan, a conventional IMRT plan was calculated and compared with regard to dose-volume histogram, conformity index and conformity number, and homogeneity index. Results: Both techniques allowed excellent target volume coverage and sufficient SB sparing. Conformity index and conformity number results for both PTV-A and PTV-B, homogeneity index for PTV-B, and SB sparing for V45, V50, Dmax, and D1% were significantly better with HT. SB sparing was significantly better for conventional IMRT at low doses (V10). Conclusions: Both HT and conventional IMRT provide optimal treatment of cervical cancer patients. The HT technique was significantly favored with regard to target conformity, homogeneity, and SB sparing. Randomized trials are needed to assess the oncological outcome, toxicity, and clinical relevance of these differences.

  4. Cervical Lymph Node Metastasis in Adenoid Cystic Carcinoma of the Larynx: A Collective International Review.

    PubMed

    Coca-Pelaz, Andrés; Barnes, Leon; Rinaldo, Alessandra; Cardesa, Antonio; Shah, Jatin P; Rodrigo, Juan P; Suárez, Carlos; Eloy, Jean Anderson; Bishop, Justin A; Devaney, Kenneth O; Thompson, Lester D R; Wenig, Bruce M; Strojan, Primož; Hamoir, Marc; Bradley, Patrick J; Gnepp, Douglas R; Silver, Carl E; Slootweg, Pieter J; Triantafyllou, Asterios; Vander Poorten, Vincent; Williams, Michelle D; Skálová, Alena; Hellquist, Henrik; Teymoortash, Afshin; Medina, Jesus E; Robbins, K Thomas; Pitman, Karen T; Kowalski, Luiz P; de Bree, Remco; Mendenhall, William M; Takes, Robert P; Ferlito, Alfio

    2016-04-01

    Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended.

  5. Three-dimensional reconstruction and quantification of cervical carcinoma invasion fronts from histological serial sections.

    PubMed

    Braumann, Ulf-Dietrich; Kuska, Jens-Peer; Einenkel, Jens; Horn, Lars-Christian; Löffler, Markus; Höckel, Michael

    2005-10-01

    The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

  6. Patient-tailored conservative surgical treatment of invasive uterine cervical squamous cell carcinoma. A review.

    PubMed

    Menczer, J

    2013-08-01

    The aim of this paper was to review currently available data regarding the results of a more conservative, patient-tailored surgical approach in selected cases of early invasive uterine squamous cell carcinoma (SCC). A PubMed search of investigations in the English language published from January 2000 to September 2012 containing the terms conservative surgery, conservative treatment, trachelectomy, parametrectomy, lymphadenectomy, sentinel lymph node biopsy and fertility sparing surgery in combination with SCC was made. Conization only is optimal for women with stage Ia1 disease mainly in tumors without lymph vascular space involvement (LVSI). In stage Ib1 patients interested to maintain reproductive capacity, vaginal or abdominal radical trachelectomy are the procedures of choice. Patients with small tumors (<2 cm), no deep invasion, no LVSI, and negative pelvic nodes are at very low risk of parametrial involvement and parametrectomy may be omitted in them. Such patients may benefit from less radical surgery and may be candidates for simple hysterectomy, simple trachelectomy, or conization with pelvic lymphadenectomy. Sentinel lymph node (SLN) biopsy is apparently a good predictor of node metastases and allows the performance of lymphadenectomy only in SLN positive cases. Thus lymphadenectomy may also be omitted in some patients. In young women with locally advanced tumors, neoadjuvant chemotherapy followed by fertility-sparing surgery may also be a feasible treatment. A more conservative, patient-tailored surgical approach in selected cases of early SCC is possible resulting in lower morbidity and preservation of fertility without compromising the outcome. PMID:24051940

  7. Radiation Therapy for Primary Carcinoma of the Extrahepatic Biliary System

    PubMed Central

    Flickinger, John C.; Epstein, Alan H.; Iwatsuki, Shunzaburo; Carr, Brian I.; Starzl, Thomas E.

    2010-01-01

    From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival. PMID:2070327

  8. Simultaneous double primary clear cell carcinomas of liver and kidney: a case report and review of literature.

    PubMed

    Zhang, Wei; Wang, Qiang; Jiang, Yan-Xia; Lu, Qing; Yu, Wen-Juan; Liu, Yan; Liu, Yu-Lin; Zhao, Hui; Zhuang, Jie; Li, Yu-Jun

    2015-01-01

    Reported herein are simultaneous double primary clear cell carcinomas arising from liver and kidney. A 63-year-old man underwent a partial wedge nephrectomy of the right kidney in a surgical resection for hepatocellular carcinoma. Coincidently, on histology the tumors in liver and kidney were consisted of clear cancer cells, which arranged in haphazardly intermixed pattern without capsules. Immunohistochemically, the clear neoplastic cells in the liver were positive for HepPar-1, GPC3, and negative for nephrogenic markers; however, renal clear neoplastic cells were positive for CD10, RCC and Pax-8, but negative to liver-derived markers. These findings led to the diagnosis of simultaneous double primary clear cell carcinomas of kidney and liver. Multiple primary carcinomas of kidney and liver, especially both are primary clear cell carcinomas, are extremely rare neoplasms, only 1 case has been reported previously until now. To our knowledge, this is a report of multiple primary carcinomas arising from the liver and kidney and reminders us of differentiation diagnosis with carcinoma metastasis. PMID:25755808

  9. Age of Diagnosis of Squamous Cell Cervical Carcinoma and Early Sexual Experience

    PubMed Central

    Edelstein, Zoe R.; Madeleine, Margaret M.; Hughes, James P.; Johnson, Lisa G.; Schwartz, Stephen M.; Galloway, Denise A.; Carter, Joseph J.; Koutsky, Laura A.

    2009-01-01

    Background Given the established links between young age at first intercourse (AFI), number of sex partners, high-risk human papillomavirus infection, and squamous cell cervical cancer (SCC), we hypothesized that women diagnosed with SCC at younger ages would be more likely to report young AFI than women diagnosed later in life. Methods We performed a population-based investigation among invasive SCC cases who were diagnosed between 1986 and 2004, were 22 to 53 years old, and lived in the metropolitan Seattle-Puget Sound region (n=333). Using multivariate linear regression, we estimated coefficients and 95% confidence intervals (CI) to assess the association between age at SCC diagnosis and AFI (<15, 15–18, ≥19) and number of sex partners before age 20 (0, 1, 2–4, 5–14, 15+), accounting for birth year and other factors. Interactions were assessed using the likelihood ratio test. Results The interval between AFI and SCC diagnosis ranged from 4 to 35 years. In a multivariate model, compared to SCC cases reporting AFI≥19, the mean age of diagnosis was 3.1 years younger for SCC cases reporting AFI<15 (CI: −5.8, −0.5) and 2.6 years younger for SCC cases reporting AFI 15–18 years (CI: −4.6, −0.6). Although number of sex partners before age 20 was associated with age at SCC diagnosis in a crude analysis, the association was not independent of AFI. However, in the AFI≥19 and AFI<15 groups, differences in effect were seen by number of sex partners before age 20 (p for interaction=0.08), with the association remaining strong and significant only in the AFI<15 group that had 2 or more partners before age 20 (coefficient: −4.2, CI: −6.3, −2.1). Conclusion Among younger and middle-aged women with SCC, early age of diagnosis was associated with early AFI, though the effect appeared to be modified by number of sex partners before age 20. PMID:19318437

  10. Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

    PubMed Central

    2014-01-01

    Background To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases. Methods We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval). Results In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65–221 structural variations (SVs) in primary tumors and 60–232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis. Conclusions We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments. PMID:24405831

  11. "Mucin secreting" and "mucinous" primary thyroid carcinomas: pitfalls in mucin histochemistry applied to thyroid tumours.

    PubMed Central

    Rigaud, C; Bogomoletz, W V

    1987-01-01

    Forty primary carcinomas of the thyroid of different histological types were reviewed and studied histochemically, with the aim of identifying and assessing "mucin secretion". The patterns of extracellular "pure alcianophilia" and "mixed alcianophilia" were noted in 7.5% and about 50% of these tumours, respectively. A critical review of the pitfalls in methods and interpretation of mucin histochemistry--as performed in previously reported cases of "mucin secreting" or "mucinous" primary thyroid tumours--is presented. The apparent "mucin secretion" described in these unusual neoplasms could be due to histochemical staining of carbohydrate components or breakdown products of thyroglobulin and colloid. Images Fig 1 Fig 2 Fig 3 PMID:3654988

  12. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    PubMed Central

    Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case presented malignant transformation of the epithelial component showing foci of squamous cell carcinoma within the GCT. PMID:26266228

  13. Molecular basis of arsenite (As+3)-induced acute cytotoxicity in human cervical epithelial carcinoma cells

    PubMed Central

    Arshad, Muhammad Nauman; Nisar, Muhammad Atif; Khurshid, Mohsin; Hussain, Syed Zajif; Maqsood, Umer; Asghar, Muhammad Tahir; Nazir, Jawad

    2015-01-01

    Background Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3) on DNA biosynthesis and cell death. Methods After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion Our results indicate that sudden exposure of cells to arsenite (As+3) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases. PMID:25922308

  14. Intracranial hypertension as the primary symptom of gastric signet-ring cell carcinoma

    PubMed Central

    Pu, Jiali; Xu, Lingjia; Yin, Xinzhen; Zhang, Baorong

    2016-01-01

    Abstract Background: Intracranial hypertension (IH) is a neurological disorder characterized by increased intracranial pressure. It is a poorly understood syndrome that most commonly manifests nonspecific symptoms such as stroke-like headache, vision changes, nausea, vomiting, and papilledema. IH has been reported in young cancer patients but never in association with gastric signet-ring cell carcinoma. Methods: Here, we discuss the case of an 18-year-old girl with gastric signet-ring cell carcinoma in which IH was the primary symptom accompanied by the even rarer symptom of cutaneous metastases. We also present a review of the relevant literature. The patient experienced frequent headaches, vomiting, and blurred vision but showed no abnormal findings on cranial imaging studies. Further examination showed multiple skin nodules on the abdomen. Then pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules were done. Results: Pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules confirmed gastric signet-ring cell carcinoma with skin metastases. Conclusion: To our knowledge, this is the first reported case of gastric signet-ring cell carcinoma primarily presenting IH and accompanied by subcutaneous metastases. This case emphasizes the importance of excluding malignancy from the differential diagnosis of IH. PMID:27583897

  15. Primary squamous cell carcinoma of the seminal vesicle: A case report

    PubMed Central

    TANG, KAIFA; SUN, FA; TIAN, YUAN; XIAO, YUEHAI; SUN, CHAO; WANG, PENGFEI

    2016-01-01

    Primary squamous cell carcinoma (SCC) is extremely rare in the seminal vesicle. A 26-year-old male patient presented with complaints of difficulty in urination for 10 years and gross hematuria for 7 months. Ultrasonography and computed tomography imaging demonstrated a large mixed solid/cystic mass lesions in the rectovesical pouch. The mass was completely resected with the open approach and was verified as a primary SCC of the seminal vesicle by post-surgical histopathological examination. Pelvic metastases were detected 28 months after the surgery. This is the third reported case of primary SCC of the seminal vesicle, and the first one in a young patient. Early diagnosis and treatment are crucial for primary SCC of the seminal vesicle. PMID:26998295

  16. Functional and Quality-of-Life Outcomes of Transoral Robotic Surgery for Carcinoma of Unknown Primary

    PubMed Central

    Durmus, Kasim; Patwa, Hafiz S.; Gokozan, Hamza N.; Kucur, Cuneyt; Teknos, Theodoros N.; Agrawal, Amit; Old, Matthew O.; Ozer, Enver

    2014-01-01

    Objectives/Hypothesis To determine speech, eating, aesthetics, social disruption, and overall quality-of-life outcomes over a year period in patients who underwent transoral robotic surgery as part of carcinoma of unknown primary diagnosis and treatment. Study Design Observational prospective study. Methods Twenty-two patients who underwent transoral robotic surgery for the management of carcinoma of unknown primary were included. Patients prospectively completed the Head and Neck Cancer Inventory during a preoperative visit, and at 3-week, 3-month, 6-month, and 12-month postoperative visits. Patients’ demographic, pathological, and follow-up information were also collected. Results The mean follow-up time was 19.8 months. There were overall declines in all quality of life scores during treatment period, which was followed by a continuous recovery. The scores immediately after transoral robotic surgery (3 weeks) were significantly higher than the scores after conclusion of adjuvant therapy (3 months) in multiple domains (P <.05) and the 6-month scores in speech (P = .02) and eating (P = .008) domains. All scores, except for eating (P = .01) returned to pre-treatment levels at 1 year. Patients with detected primaries displayed similar quality-of-life scores compared to patients with occult primaries. Human papillomavirus status and type of adjuvant treatment had no significant impact on quality of life. Conclusions Transoral robotic surgery is a promising, minimally invasive procedure for the surgical management of carcinoma of unknown primary. Patients maintain high functional and quality-of-life status at 1 year after surgery. PMID:24706455

  17. Inactivation of the Human Papillomavirus E6 or E7 Gene in Cervical Carcinoma Cells by Using a Bacterial CRISPR/Cas RNA-Guided Endonuclease

    PubMed Central

    Kennedy, Edward M.; Kornepati, Anand V. R.; Goldstein, Michael; Bogerd, Hal P.; Poling, Brigid C.; Whisnant, Adam W.; Kastan, Michael B.

    2014-01-01

    ABSTRACT High-risk human papillomaviruses (HPVs), including HPV-16 and HPV-18, are the causative agents of cervical carcinomas and are linked to several other tumors of the anogenital and oropharyngeal regions. The majority of HPV-induced tumors contain integrated copies of the normally episomal HPV genome that invariably retain intact forms of the two HPV oncogenes E6 and E7. E6 induces degradation of the cellular tumor suppressor p53, while E7 destabilizes the retinoblastoma (Rb) protein. Previous work has shown that loss of E6 function in cervical cancer cells induces p53 expression as well as downstream effectors that induce apoptosis and cell cycle arrest. Similarly, loss of E7 allows increased Rb expression, leading to cell cycle arrest and senescence. Here, we demonstrate that expression of a bacterial Cas9 RNA-guided endonuclease, together with single guide RNAs (sgRNAs) specific for E6 or E7, is able to induce cleavage of the HPV genome, resulting in the introduction of inactivating deletion and insertion mutations into the E6 or E7 gene. This results in the induction of p53 or Rb, leading to cell cycle arrest and eventual cell death. Both HPV-16- and HPV-18-transformed cells were found to be responsive to targeted HPV genome-specific DNA cleavage. These data provide a proof of principle for the idea that vector-delivered Cas9/sgRNA combinations could represent effective treatment modalities for HPV-induced cancers. IMPORTANCE Human papillomaviruses (HPVs) are the causative agents of almost all cervical carcinomas and many other tumors, including many head and neck cancers. In these cancer cells, the HPV DNA genome is integrated into the cellular genome, where it expresses high levels of two viral oncogenes, called E6 and E7, that are required for cancer cell growth and viability. Here, we demonstrate that the recently described bacterial CRISPR/Cas RNA-guided endonuclease can be reprogrammed to target and destroy the E6 or E7 gene in cervical carcinoma

  18. E6 and E7 gene silencing results in decreased methylation of tumor suppressor genes and induces phenotype transformation of human cervical carcinoma cell lines

    PubMed Central

    Long, Jia; Shen, Danbei; Zhou, Wuqing; Zhou, Qiyan; Yang, Jia; Jiang, Mingjun

    2015-01-01

    In SiHa and CaSki cells, E6 and E7-targeting shRNA specifically and effectively knocked down human papillomavirus (HPV) 16 E6 and E7 at the transcriptional level, reduced the E6 and E7 mRNA levels by more than 80% compared with control cells that expressed a scrambled-sequence shRNA. E6 and E7 repression resulted in down-regulation of DNA methyltransferase mRNA and protein expression, decreased DNA methylation and increased mRNA expression levels of tumor suppressor genes, induced a certain apoptosis and inhibited proliferation in E6 and E7 shRNA-infected SiHa and CaSki cells compared with the uninfected cells. Repression of E6 and E7 oncogenes resulted in restoration of DNA methyltransferase suppressor pathways and induced apoptosis in HPV16-positive cervical carcinoma cell lines. Our findings suggest that the potential carcinogenic mechanism of HPV16 through influencing DNA methylation pathway to activate the development of cervical cancer exist, and maybe as a candidate therapeutic strategy for cervical and other HPV-associated cancers. PMID:26329329

  19. Expression of Girdin in primary hepatocellular carcinoma and its effect on cell proliferation and invasion.

    PubMed

    Cao, Ke; Lu, Can; Han, Shuang; Zou, Qiong; Li, Jingjing; Xie, Dingfang; He, Siqi; Yu, Li; Zhou, Jianda; Peng, Xiaowei; Cao, Peiguo

    2015-01-01

    Girdin has been proven to play a vital role in the process of proliferation, apoptosis, and invasion in various cancer cells, yet the underlying molecular mechanism in primary hepatocellular carcinoma (HCC) has not yet been clarified. Thereafter, we performed immunohistochemistry to detect the expression of Girdin in 40 primary HCC tissues and 30 matched adjacent tissues using hepatic carcinoma tissue microarray. Our data showed that the positive expression rate of Girdin in hepatocellular carcinoma tissues was 67.5%, higher than that found in adjacent tissues of 16.7% (P < 0.05). It closely correlates to tumor size, T stage, TNM stage and Edmondson-Steiner stage (P < 0.05) of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In summary, we suggest that the oncogenic role of Girdin could provide new molecular target for the treatment of HCC.

  20. An evidence on G2/M arrest, DNA damage and caspase mediated apoptotic effect of biosynthesized gold nanoparticles on human cervical carcinoma cells (HeLa)

    SciTech Connect

    Jeyaraj, M.; Arun, R.; Sathishkumar, G.; MubarakAli, D.; Rajesh, M.; Sivanandhan, G.; Kapildev, G.; Manickavasagam, M.; Thajuddin, N.; Ganapathi, A.

    2014-04-01

    Highlights: • Gold nanoparticles (AuNPs) have been synthesized using Podophyllum hexandrum L. • AuNPs induces the oxidative stress to cell death in human cervical carcinoma cells. • It activates the caspase-cascade to cellular death. • It is actively blocks G2/M phase of cell cycle. - Abstract: Current prospect of nanobiotechnology involves in the greener synthesis of nanostructured materials particularly noble metal nanoparticles for various biomedical applications. In this study, biologically (Podophyllum hexandrum L.) synthesized crystalline gold nanoparticles (AuNPs) with the size range between 5 and 35 nm were screened for its anticancereous potential against human cervical carcinoma cells (HeLa). Stoichiometric proportion of the reaction mixture and conditions were optimized to attain stable nanoparticles with narrow size range. Different high throughput techniques like transmission electron microscope (TEM), X-ray diffraction (XRD) and UV–vis spectroscopy were adopted for the physio-chemical characterization of AuNPs. Additionally, Fourier transform infrared spectroscopy (FTIR) study revealed that the water soluble fractions present in the plant extract solely influences the reduction of AuNPs. Sublimely, synthesized AuNPs exhibits an effective in vitro anticancer activity against HeLa cells via induction of cell cycle arrest and DNA damage. Furthermore, it was evidenced that AuNPs treated cells are undergone apoptosis through the activation of caspase cascade which subsequently leads to mitochondrial dysfunction. Thereby, this study proves that biogenic colloidal AuNPs can be developed as a promising drug candidature for human cervical cancer therapy.

  1. Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.

    PubMed

    Tornos, Carmen; Soslow, Robert; Chen, Shirley; Akram, Muzaffar; Hummer, Amanda J; Abu-Rustum, Nadeen; Norton, Larry; Tan, Lee K

    2005-11-01

    Metastatic breast carcinoma to the ovary is sometimes difficult to differentiate from primary ovarian carcinoma. This problem is often encountered in breast carcinoma patients who develop adnexal masses. ER and PR can be positive in a high percentage of breast and ovarian carcinomas, and therefore cannot be used in the differential diagnosis of these entities. WT1 and CA125 have been identified as possible markers for ovarian cancer. However, no studies have been done that specifically compare the immunophenotype of breast carcinoma metastatic to ovary with that of primary ovarian cancer. Thirty-nine cases of metastatic breast carcinoma to the ovary, 36 primary breast carcinomas, and 42 primary ovarian carcinomas were examined immunohistochemically for the expression of WT1, CA125, carcinoembryonic antigen, MUC2, MUC1, and GCDFP. The percentage of cells stained and the intensity of staining were recorded. Thirty-two ovarian carcinomas (76%) were positive for WT1, including 31 of 33 (94%) serous carcinomas. Most of them had strong and diffuse staining. None of the breast cancers either primary or metastatic to the ovary expressed WT1. Thirty-eight (90%) ovarian carcinomas were positive for CA125, most of them with strong and diffuse staining. Most breast carcinomas were negative for CA125, with only 6 (16%) of the primary ones and 5 (12%) of the metastatic showing weak and focal positivity. All ovarian carcinomas were negative for GCDFP. Five primary breast cancers (14%) and 17 (43%) metastatic to the ovary were positive for GCDFP. Nine (21%) ovarian carcinomas, 8 (22%) primary breast carcinomas, and 13 (33%) metastatic to the ovary were positive for carcinoembryonic antigen. Almost all tumors examined were positive for MUC1 (100% ovarian carcinomas, 100% primary breast carcinomas, and 95% metastatic breast carcinomas to ovary). MUC2 was positive in 10 (24%) ovarian carcinomas, 3 (8%) primary breast cancers, and 12 (30%) metastases to the ovary. The presence of

  2. Heat-activated thermosensitive liposomal cisplatin (HTLC) results in effective growth delay of cervical carcinoma in mice.

    PubMed

    Dou, Yannan N; Zheng, Jinzi; Foltz, Warren D; Weersink, Robert; Chaudary, Naz; Jaffray, David A; Allen, Christine

    2014-03-28

    Cisplatin (CDDP) has been identified as the primary chemotherapeutic agent for the treatment of cervical cancer, but dose limiting toxicity is a key issue associated with its clinical application. A suite of liposome formulations of CDDP has been developed in efforts to reduce systemic toxicity, but their therapeutic advantage over the free drug has been modest due to insufficient drug release at the tumor site. This report describes the development of a novel heat-activated thermosensitive liposome formulation containing CDDP (HTLC) designed to release approximately 90% of the loaded drug in less than 5min under mild heating conditions (42°C). Physico-chemical characteristics of HTLC were assessed in terms of gel to liquid crystalline phase transition temperature (Tm), drug loading efficiency, particle size, and stability. The pharmacokinetic profile and biodistribution of HTLC in non-tumor-bearing mice were evaluated over a 24h period. A sophisticated spatio-temporal elucidation of HTLC release in tumor-bearing mice was achieved by way of real-time monitoring using a magnetic resonance (MR) imaging protocol, wherein a custom-built laser-based conformal heat source was applied at the tumor volume to trigger the release of HTLC co-encapsulated with the MR contrast agent gadoteridol (Gd-HP-DO3A). MR thermometry (MRT) demonstrated that a relatively uniform temperature distribution was achieved in the tumor volume using the external laser-based heating setup. In mice bearing subcutaneously-implanted ME-180 cervical tumors, the combination of HTLC and heat resulted in a 2-fold increase in tumor drug levels at 1h post-administration compared to HTLC without heating. Furthermore, the overall tumor accumulation levels for the HTLC groups (with and without heat) at 1h post-injection were significantly higher than the corresponding free CDDP group. This translated into a significant improvement in therapeutic efficacy evaluated as tumor growth delay (p<0.05) for the heated

  3. Incidental finding of bilateral papillary thyroid carcinoma in a patient with primary hyperparathyroidism.

    PubMed

    Alavi, Mehr Sadat; Azarpira, Negar; Mojallal, Mehra

    2010-01-01

    Primary hyperparathyroidism (PHP) affects 0.5%-1% of the adult population and presents with classical signs of renal lithiasis, cholecystolithiasis, gastrointestinal ulcerations, depression, and osteoporosis. Parathyroid adenoma, hyperplasia and rarely carcinoma are the underlying pathology. Synchronous thyroid and parathyroid pathologies are described in multiple endocrine neoplasia. We report a case of a 47 years old woman with non-syndromic concomitant occurrence of bilateral non-medullary thyroid carcinoma diagnosed by histopathology, and with PHP confirmed by (99m)Tc-MIBI scintigraphy, hypercalcemia and elevated serum parathyroid hormone. A head and neck surgeon needs to be aware of the possible coexistence of thyroid and parathyroid lesions. To our knowledge, this is the first report of concomitant PHP and bilateral papillary thyroid cancer in the literature. In conclusion, it is optimal to remove both tumors in one operative procedure. Therefore careful thyroid evaluation should be considered for all patients with PHP.

  4. Get Vaccinated! and Get Tested! Developing Primary and Secondary Cervical Cancer Prevention Videos for a Haitian Kreyòl-Speaking Audience.

    PubMed

    Frett, Brigitte; Aquino, Myra; Fatil, Marie; Seay, Julia; Trevil, Dinah; Fièvre, Michèle Jessica; Kobetz, Erin

    2016-05-01

    Although routine screening reduces cervical cancer rates between 60% and 90%, thousands of women worldwide are diagnosed with the disease on an annual basis because of inadequate screening. Haitian women in South Florida experience a disproportionate burden of cervical cancer, with disease rates 4 times higher than the average for women in Miami. An ongoing community-based participatory research initiative to assess and reduce this burden has revealed that a complex interplay of factors contributes to a lack of access to screening in this community, including socioeconomics, language barriers, and traditional understandings of health and disease. In an effort to address some of these barriers and encourage uptake of primary and secondary cervical cancer prevention strategies, 2 videos on cervical cancer prevention were created using a community-based participatory research framework. The video screenplays were created by a Haitian screenwriter using evidence-based medical information provided by academic researchers. The films feature Haitian actors speaking a Haitian Kreyòl dialogue with a storyline portraying friends and family discussing human papillomavirus disease and vaccination, Papanicolaou testing, and cervical cancer. Focus groups held with Haitian women in South Florida suggested that the films are engaging; feature relatable characters; and impact knowledge about human papillomavirus, cervical cancer development, and current prevention recommendations.

  5. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  6. Merkel cell carcinoma of unknown primary site; case presentation and review of the literature.

    PubMed

    Kontis, Elissaios; Vezakis, Antonios; Pantiora, Eirini; Stasinopoulou, Sotiria; Polydorou, Andreas; Voros, Dionysios; Fragulidis, Georgios P

    2015-12-01

    Merkel cell carcinoma (MCC) is a rare skin malignancy associated with sun exposure and considered as a Neuroendocrine Tumor due to its characteristic histologic features. However there is increasing number of reports of Unknown Primary MCC's (UPMCC). Although initially UPMCC was considered a variant of known primary MCC, there is growing evidence that it could represent a different clinical entity. We present the case of a 60 year-old male patient who was referred to our department for surgical management of lymph node disease for UPMCC. The patient had undergone excisional biopsy of an inguinal lump, which was found to be an infiltrated lymph node by MCC. The patient underwent full imaging staging including a PET/CT, which failed to identify a primary site, and revealed only intra-abdominal lymph node disease. The patient underwent extended retroperitoneal and inguinal lymph node dissection and remains free of recurrence 16 months postoperatively. PMID:26904196

  7. Primary adenoid cystic carcinoma of the trachea with thyroid invasion: a case report and literature review

    PubMed Central

    Qi, Dianjun; Feng, Liang; Li, Jian; Liu, Bing; Zhang, Qingfu

    2016-01-01

    Primary adenoid cystic carcinoma (ACC) of the trachea with thyroid invasion is very rare. In this report, we present a 46-year-old man with primary ACC of the trachea with thyroid invasion. ACC invasion of the thyroid is very rare and is easily misdiagnosed. The patient sought consultation due to a 6-month history of dysphagia and associated dyspnea. A contrast-enhanced computed tomography scan obtained at the time of admission revealed bilateral thyroid masses and tracheal wall thickening. The thyroid masses were fused to the trachea and the esophagus without discernible borders, intraoperatively. Frozen pathology suggested poorly differentiated cancer, and a bilateral partial thyroidectomy was performed. Postoperative pathology revealed primary tracheal ACC with thyroid invasion. The patient died 1 month after surgery. We have also summarized the literature on the clinical presentation, diagnosis, and treatment of thyroid-invasive ACC. PMID:27785076

  8. Clinical outcome of primary small cell carcinoma of the urinary bladder

    PubMed Central

    Hou, Chen-Pang; Lin, Yu-Hsiang; Chen, Chien-Lun; Chang, Phei-Lang; Tsui, Ke-Hung

    2013-01-01

    Purpose Primary small cell carcinoma of the urinary bladder is a rare malignant disease. It accounts for less than 1% of all urinary bladder carcinomas. The purpose of this study is to review the clinical features, the treatment modalities, and the overall survival of these patients. We also compare the clinical outcomes between patients of bladder small cell carcinoma (SCC) and bladder urothelial carcinoma (UC). Materials and methods We reviewed the charts of patients with bladder tumors from January 1995 to December 2012 in the Chang Gung Memorial Hospital. A total of 2421 malignant bladder tumor patients were reviewed and there were 18 patients who were diagnosed with primary bladder SCC. The patients’ characteristics, including age, gender, smoking history, presented symptoms, tumor size, locations, clinical stages, treatment modalities, pathology appearance, recurrence conditions, and survival conditions were all recorded. We also compared the clinical outcomes and the overall survival rates between patients with bladder SCC and those with UC. Results Bladder SCC accounted for about 0.74% of all bladder malignancies in our institution. The mean age at diagnosis was 70.67 years, and the male-to-female ratio was 2.6:1. Thirteen patients had a history of cigarette smoking. All patients presented with symptoms of gross hematuria, and three of them had bladder tamponade requiring blood clot evacuation by cystoscopy. Only one patient had T1 disease, ten patients had stage III disease, and seven patients had lymph node or distant metastasis (stage IV disease). The mean tumor size was 4.29 cm in diameter. For the majority (61.11%) of patients, SCC coexisted with UC components. The average survival time was 10.92 months. Patients with bladder SCC had worse overall survival rates than those of stage III and stage IV bladder UC. Performing radical cystectomy does not significantly improve their overall survival rates. None of the clinicopathologic parameters, including

  9. Fascin upregulation in primary head and neck squamous cell carcinoma is associated with lymphatic metastasis

    PubMed Central

    PAPASPYROU, KONSTANTINOS; BROCHHAUSEN, CHRISTOPH; SCHMIDTMANN, IRENE; FRUTH, KAI; GOUVERIS, HARALAMPOS; KIRCKPATRICK, JAMES; MANN, WOLF; BRIEGER, JUERGEN

    2014-01-01

    Fascin is an actin-bundling protein that is associated with cellular motility and cancer-cell invasion. The present study aimed to examine the expression of fascin in head and neck squamous cell carcinoma (HNSCC) and its potential use as a biomarker. In a prospective study with a median follow-up time of 48.8 months, tumor tissues, adjacent healthy tissues and cervical lymph node metastases were collected from 25 patients and analyzed by immunohistochemistry. The specimens were scored according to the intensity of fascin staining and the percentage of tumor cells stained using a semi-quantitative scoring approach; the data were analyzed and correlated with clinical follow-up observations. All of the investigators were blinded to the origin of the specimens. The expression levels of fascin were significantly increased in the tumor tissues (P=0.03) and lymph node metastases (P=0.03) compared with that of the normal tissues. The high expression level of fascin in the tumor tissues was correlated with the N-status, however, not with overall survival. Therefore, fascin may be a suitable marker for the prediction of regional lymphatic metastasis in HNSCC. PMID:24932286

  10. Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI Measurements.

    PubMed

    Zhang, H; Zhang, G; Oudkerk, M

    2012-03-01

    This study evaluated the roles of different dynamic susceptibility contrast magnetic imaging (DSC MRI) measurements in discriminating between brain metastases derived from four common primary carcinomas. Thirty-seven patients with brain metastases were enrolled. Relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor and peritumoral edema were measured. Metastases were grouped by their primary tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and peritumoral edema of all brain metastases (n=37) were 2.79 ± 1.73, 2.56 ± 2.11, 1.21 ± 0.48 and 1.05 ± 0.53, 0.86 ± 0.40, 1.99 ± 0.41, respectively. The tumoral rCBV (5.26 ± 1.89) and rCBF (5.32 ± 3.28) of renal metastases were greater than those of the other three metastases (P<0.05). The tumoral rMTT (1.58 ± 0.77) of breast metastases was statistically greater than that (0.96 ± 0.31) of gastrointestinal metastases (P=0.013). No statistical difference was found between peritumoral rCBV, rCBF and rMTT (P>0.05). Evaluating various DSC MRI measurements can provide complementary hemodynamic information on brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate between brain metastases originating from different primary carcinomas. The peritumoral DSC MRI measurements had limited value in discriminating between brain metastases.

  11. Hepatic Resection in Primary Liver Carcinoma: Prolonged Survival in Two Nigerian Patients

    PubMed Central

    Awojobi, O. A.; Ayoola, E. A.; Junaid, T. A.

    1982-01-01

    Two Nigerian patients with primary liver carcinoma (PLC) who had wedge resection with prolonged survival are described. The localization of their tumors to the right hepatic lobe and their polypoidal nature were favorable factors that allowed early detection and treatment. The surgical treatment of PLC is reviewed. It is suggested that suitable African patients with PLC be offered resection as a modality of treatment coupled with adequate follow-up to detect and deal with recurrence early. ImagesFigure 1Figure 2 PMID:7120488

  12. Primary intraosseous squamous cell carcinoma derived from a maxillary cyst: A case report and literature review

    PubMed Central

    MORITA, TAKUMA; YAMASHIRO, MASASHI; KAYAMORI, KOU; MIZUTANI, MIHO; NAKAKUKI, KOICHI; MICHI, YASUYUKI; UZAWA, NARIKAZU; IZUMO, TOSHIYUKI; HARADA, KIYOSHI

    2016-01-01

    Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant central jaw tumor derived from odontogenic epithelial remnants. PIOSCC predominantly affects the mandible, although both jawbones may be involved. This case report describes a PIOSCC type 2 of the maxilla in a 37-year-old man, treated by partial maxillectomy. Histopathologically, the tumor was diagnosed as PIOSCC derived from an odontogenic cyst. Postoperatively, the patient has been followed up for 53 months, with no recurrence of the disease. We herein describe the clinical details, treatment results and histopathological characteristics of a rare case of PIOSCC derived from a maxillary odontogenic cyst with reference to the relevant literature. PMID:27073661

  13. Primary hyperparathyroidism caused by a parathyroid carcinoma in a 16-year-old male neutered cat with concurrent chronic kidney disease.

    PubMed

    Faucher, Mathieu R; Freiche, Valérie; Bongrand, Yannick; German, Alexander J

    2014-01-01

    A 16-year-old domestic shorthaired cat with chronic kidney disease was presented with a subacute history of weakness and anorexia. Severe hypercalcaemia was identified and attributed to a cervical mass, diagnosed as a parathyroid carcinoma after surgery. Renal function, as evaluated by plasma creatinine, initially worsened during hypercalcaemia but fully returned to previously documented values two months post-operatively.

  14. Cost-effectiveness in the diagnosis and treatment of carcinoma of unknown primary origin

    PubMed Central

    Levine, Mark N.; Drummond, Michael F.; Labelle, Roberta J.

    1985-01-01

    Between 2% and 9% of patients with cancer present with metastatic nonsquamous cell carcinoma of unknown primary origin. Traditionally, a series of investigations is undertaken to locate the primary origin of the tumour, although many of these tests are often painful or distressing to patients, unsuccessful in locating the primary site and costly to the health care system. Moreover, even if a tumour is found it usually cannot be treated surgically. However, a small number of cancers of unknown primary origin can be cured, arrested or effectively palliated with systemic treatment. This study compares the costs and outcomes of the current practice of comprehensively searching for the primary tumour with those of an alternative, limited approach that identifies only the primary tumours for which relatively effective systemic therapy exists. Decision trees were constructed for the two diagnostic approaches and their associated therapeutic options. Costs and probabilities were integrated with published data on the survival of patients with each type of cancer. The results indicate that the comprehensive diagnostic strategy may increase 1-year survival rates from 11.0% to 11.5%. On the basis of Ontario cost data it is calculated that the additional costs of a comprehensive search for 1000 patients will range from approximately $2 million to $8 million, depending on the subsequent treatment strategy. PMID:3933808

  15. Nephron sparing endoscopic treatment for primary carcinoma of the renal calyx: A case report and literature review

    PubMed Central

    WANG, QI; OU, TONG-WEN; XU, JIA-WEI; LI, JIN; BORAZJANI, ALI; JIA, CHUN-SONG; WANG, XU; YAN, HAO

    2016-01-01

    Primary carcinoma of the renal calyx is extremely rare. The present study reported nephron sparing endoscopic treatment for primary carcinoma of the renal calyx. An 81-year-old female presented with a 1-year history of intermittent painless gross hematuria. Computed tomography and X-ray of the urinary tract were unable to definitively identify any lesion. Flexible ureteroscopic examination revealed a tumor with epicenter in the lower calyx of the right kidney, with additional involvement around the calyx. Biopsies were obtained and pathology revealed low-grade urothelial carcinoma. Considering additional co-morbidities, the patient elected to undergo endoscopic management with thulium laser. The present report described the feasibility of flexible ureteroscopic thulium laser resection for the treatment of renal calyx carcinoma. PMID:27330785

  16. Long-Term Survival After Local Resection of Cervical Esophageal Cancer.

    PubMed

    Ali Mohammad, Farah Hanif; Go, Pauline; Ghanem, Tamer; Stachler, Robert; Hammoud, Zane

    2015-06-01

    Squamous cell carcinoma of the esophagus may be seen in patients with history of head and neck malignancies. Anatomic factors may limit management options. We present a case of second primary early cervical esophageal squamous cell cancer managed by local resection with reconstruction using a radial forearm flap. PMID:26046877

  17. HPV Genotypes in High Grade Cervical Lesions and Invasive Cervical Carcinoma as Detected by Two Commercial DNA Assays, North Carolina, 2001–2006

    PubMed Central

    Hariri, Susan; Steinau, Martin; Rinas, Allen; Gargano, Julia W.; Ludema, Christina; Unger, Elizabeth R.; Carter, Alicia L.; Grant, Kathy L.; Bamberg, Melanie; McDermott, James E.; Markowitz, Lauri E.; Brewer, Noel T.; Smith, Jennifer S.

    2012-01-01

    Background HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Methods Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. Findings LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. Conclusions We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction. PMID:22479516

  18. Pure Primary Squamous Cell Carcinoma of the Breast Arising from the Epithelium of a Complex Mammary Cyst: A Case Report.

    PubMed

    Tihan, Deniz; Hepgul, Gülcin; Kucukyilmaz, Meltem; Sar, Mehmet; Guven, Hakan

    2011-04-01

    As an uncommon desease, pure primary squamous cell carcinoma (SCC) of the breast is a malign and aggressive tumoral lesion. A 47 year-old woman was admitted to our clinic complaining of mastalgy and a mass in her right breast. Ultrasound examinations revealed 4 cm heterogenic cystic mass. Wherefore the magnetic resonance imaging showed suspicious malignity, total excision of the mass was performed. Histopathologic examimation revealed squamous cell carcinoma. PMID:21461996

  19. Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada

    PubMed Central

    Popadiuk, C.; Gauvreau, C.L.; Bhavsar, M.; Nadeau, C.; Asakawa, K.; Flanagan, W.M.; Wolfson, M.C.; Coldman, A.J.; Memon, S.; Fitzgerald, N.; Lacombe, J.; Miller, A.B.

    2016-01-01

    Background In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. Methods We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. Results Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. Conclusions Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes. PMID:26985148

  20. Squamous cell carcinoma arising from an unknown primary site metastasizing to the stomach: A case report

    PubMed Central

    WANG, GUANGYAO; CHEN, PING; SHI, LEI; ZHAO, WEI

    2014-01-01

    Primary squamous cell carcinoma (SCC) may originate elsewhere in the body, including the head, neck, lung, bronchus, cervix uteri, esophagus and cardia, and metastasize to the stomach. In the present report, a case is presented of an SCC, which arose from an unknown primary site and metastasized to the stomach of a 59-year-old male. The tumor was located in the interspace between the liver and the stomach. It involved the placenta percreta, lamina muscularis and submucosa, however, had already metastasized to a regional lymph node at the time of surgery. No SCC was observed in other organs on physical examination, which included positron emission tomography-computed tomography. In the follow-up period, there was no evidence of additional malignant tumors in the patient; therefore, the origin of the tumor was speculative. To the best of our knowledge, this is the first case report regarding a tumor of this type. PMID:24944669

  1. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers

    PubMed Central

    Qiu, Zhixin; Zou, Keke; Zhuang, Liping; Qin, Jianjie; Li, Hong; Li, Chao; Zhang, Zhengtao; Chen, Xiaotao; Cen, Jin; Meng, Zhiqiang; Zhang, Haibin; Li, Yixue; Hui, Lijian

    2016-01-01

    Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine. PMID:27273737

  2. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers.

    PubMed

    Qiu, Zhixin; Zou, Keke; Zhuang, Liping; Qin, Jianjie; Li, Hong; Li, Chao; Zhang, Zhengtao; Chen, Xiaotao; Cen, Jin; Meng, Zhiqiang; Zhang, Haibin; Li, Yixue; Hui, Lijian

    2016-06-07

    Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.

  3. Thallium-201-chloride and technetium-99m-MIBI SPECT of primary and metastatic lung carcinoma.

    PubMed

    Kashitani, N; Makihara, S; Maeda, T; Eda, R; Takeyama, H; Hiraki, Y

    1999-01-01

    We compared technetium-99m-MIBI (Tc-99m MIBI) with thallium-201-chloride (Tl-201) SPECT imaging in patients with lung carcinoma. In addition, we compared the imaging characteristics of Tl-201 and Tc-99m MIBI after radiation therapy. Thirty-seven patients with primary lung carcinoma were evaluated with SPECT imaging for metastasis to the mediastinal lymph nodes and brain. Patients were imaged with Tl-201 chloride images 10 and 180 min after injection. Patients were also imaged 10 min after injection of Tc-99m MIBI. The sensitivity of Tl-201 SPECT for the primary lesion and brain metastasis was 97.1% and 70.0% respectively at 10 min and 97.1% and 60.0% at 180 min. The sensitivity of Tc-99m MIBI SPECT was 97.1% (for the identification of the primary lesion) and 50.0% (for the detection of brain metastasis) at 10 min. The uptake ratios (count in tumor/count in normal lung or brain) at 10 min on the Tl-201 SPECT and on the Tc-99m MIBI SPECT were not significantly different for the primary tumor or for brain metastasis. The uptake ratios were better for Tc-99m MIBI than for Tl-201 [2.82 vs. 1.99 (p<0.05)] for mediastinal lymph nodes. Decreasing uptake ratios and retention index with both agents after radiation therapy are concordant to the follow-up clinical course. Tc-99m MIBI SPECT is more sensitive in the detection of metastasis to mediastinal lymph nodes than Tl-201 SPECT.

  4. Randomized Comparison of Intra-Arterial Chemotherapy Versus Intra-Arterial Chemotherapy and Gelfoam Embolization for Treatment of Advanced Cervical Carcinoma

    SciTech Connect

    Ikeda, O. Mizukami, N.; Murata, Y.; Arakawa, A.; Katabuchi, H.; Okamoto, H.; Yasunaga, T.; Tsunawaki, A.; Yamashita, Y.

    2005-12-15

    Purpose:We evaluated the effects of intra-arterial infusion therapy by comparing the results obtained with a combination of intra-arterial anticancer drugs with and without transcatheter arterial embolization (TAE) in patients with cervical cancer.Methods:Between April 1999 and March 2003, intra-arterial therapy was administered to 45 patients (mean age 49 years) with cervical cancer. Of these, 18 had stage IIb , 4 had stage IIIa, 19 had stage IIIb, and 4 had stage IVb cancer; the histopathologic types were squamous cell carcinoma (n = 35), adenocarcinoma (n = 8), and adenosquamous carcinoma (n = 2). A total of 45 patients gave their informed consent and were randomized on a continuous basis into one of three groups according to the therapeutic protocols: group A consisted of 15 patients who received cisplatin, group B consisted of 17 patients who received cisplatin, mitomycin, doxorubicin hydrochloride, and 5-fluorouracil, and group C consisted of 13 patients who received cisplatin and TAE. Each protocol was administered twice with a 3 week interval between treatments. The efficacy of treatment was evaluated on the basis of the tumor reduction ratio (%) using MR imaging and the side effects were analyzed.Results:In groups A, B, and C, the tumor reduction ratio was 54%, 84%, and 86%, respectively; it was significantly greater in groups B and C than in group A (p < 0.01). The difference between groups B and C was not statistically significant. Although all group C patients developed severe pain after TAE, the pain was controlled with analgesics. Thrombocytopenia occurred in 6 of 17 (35%) group B patients.Conclusion:Group B and C patients had better tumor reduction than those in group A. Fewer hematologic complications occurred in group C patients compared with group B.

  5. Quantum dots (QDs) restrain human cervical carcinoma HeLa cell proliferation through inhibition of the ROCK-c-Myc signaling.

    PubMed

    Chen, Liqun; Qu, Guangbo; Zhang, Changwen; Zhang, Shuping; He, Jiuyang; Sang, Nan; Liu, Sijin

    2013-03-01

    Cancers often cause significant morbidity and even death to patients. To date, conventional therapies, such as chemotherapy, radiation and surgery, are often limited; meanwhile, novel anticancer therapeutics are urgently needed to improve clinical treatments. Rapid application of nanotechnology and nanomaterials represents a promising vista for the development of anti-cancer therapeutics. However, how to integrate the novel properties of nanotechnology and nanomaterials into cancer treatment warrants close investigation. In the current study, we report a novel finding about the inhibitory effect of CdSe quantum dots (QDs) on Rho-associated kinase (ROCK) activity in cervical carcinoma HeLa cells associated with the attenuation of the ROCK-c-Myc signaling. We mechanistically demonstrated that QD-conducted ROCK inhibition greatly diminished c-Myc protein stability due to reduced phosphorylation, and also suppressed its activity in transcribing target genes (e.g. HSPC111). Thus, the treatment of QDs greatly restrained HeLa cell growth by inducing cell cycle arrest at G1 phase due to the reduced ability of c-Myc in driving cell proliferation. Additionally, since HSPC111, one of the c-Myc targets, is involved in regulating cell growth through ribosomal biogenesis and assembly, the downregulation of HSPC111 could also contribute to diminished proliferation in HeLa cells upon QD treatment. These results together suggested that inhibition of ROCK activity or ROCK-mediated c-Myc signaling in tumor cells upon QD treatment might represent a promising strategy to restrain tumor progression for human cervical carcinoma.

  6. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report

    PubMed Central

    2016-01-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect.

  7. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report.

    PubMed

    Kim, Tae-Hwan; Kim, Chul-Hwan

    2016-08-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect. PMID:27595090

  8. Spindle cell carcinoma of the tongue combined with double primary cancer of the thyroid gland: a case report

    PubMed Central

    2016-01-01

    Spindle cell carcinoma (SpCC) is referred to as a variant of oral squamous cell carcinoma. It is also known as "sarcomatoid squamous cell carcinoma" because it consists of normal squamous carcinoma cells with spindle-shaped cells that appear similar to a sarcoma. The term, "second primary tumor" (SPT) or "double primary tumor", is proposed for a second tumor that develops independently from the first. SPTs can present as either synchronous or metachronous lesions. Synchronous SPTs are defined as tumors occurring simultaneously or within 6 months after the first tumor. The patient in this case, whose primary tumor was in the tongue, was diagnosed with SpCC with metastases to both neck lymph nodes. This case also exhibited a second primary cancer as a synchronous lesion in the thyroid gland, which is uncommon. All carcinomas, both in the tongue and thyroid gland, were removed surgically, and especially in the tongue, an anterolateral thigh free flap was performed successfully to replace the defect. PMID:27595090

  9. Evaluation of histomorphological and immunohistochemical parameters as biomarkers of cervical lymph node metastasis in squamous cell carcinoma of oral cavity: A retrospective study

    PubMed Central

    Suresh, TN; Hemalatha, A; Harendra Kumar, ML; Azeem Mohiyuddin, SM

    2015-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) is seen worldwide but is more common in India. Lymph node (LN) metastasis has been shown to be the strongest prognostic factor in OSCC. Many histopathological and immunohistochemical markers have been studied to predict the LN metastasis. Aims: To identify clinicopathological factors and immunohistochemical (IHC) biomarkers which predict cervical metastasis in OSCC patients. Study and Design: A total of 105 cases of OSCC were taken up for our study. Histopathological parameters such as tumor thickness, depth, degree of differentiation, pattern of invasion (POI), lymphovascular and neural invasion were assessed. IHC was done on all cases using antibodies against Ki-67, cyclin D, E-cadherin, p53, CD31 and each antibody was assessed according to the standard protocol. Statistical Analysis: To calculate the relation between clinical, histopathological parameter, IHC marker and the occurrence of LN metastasis, chi-square test was used. Variables were tested using multivariate logistic regression method to assess the predictive significance. Results: Out of 105 cases studied, 29 cases showed LN metastasis. Maximum numbers of cases affected were females with involvement of buccal mucosa. We found significant association of cervical LN metastasis with high grade of differentiation, lack of E-cadherin expression, high Ki-67 and cyclin D1 expression. In our study; tumor depth, thickness, extent of peritumoral lympho-plasmacytic infiltration, presence of eosinophils, tumor nest type, p53 and microvessel density (MVD) showed no significant correlation. Conclusion: Significant association of cervical LN metastasis with high grade of differentiation, lack of E-cadherin expression, high Ki-67 and cyclin D1 expression was seen. PMID:26097301

  10. HPV16 E2 is an immediate early marker of viral infection, preceding E7 expression in precursor structures of cervical carcinoma.

    PubMed

    Xue, Yuezhen; Bellanger, Sophie; Zhang, Wenying; Lim, Diana; Low, Jeffrey; Lunny, Declan; Thierry, Françoise

    2010-07-01

    The viral E2 gene product plays a crucial role in the human papillomavirus (HPV) vegetative cycle by regulating both transcription and replication of the viral genome. E2 is a transcriptional repressor of the E6 and E7 viral oncogenes for HPV types 16 and 18, which are involved in cervical cancers. Using new polyclonal antibodies against the HPV16 E2 protein, we showed that E2 is expressed at various precursor stages of cervical carcinoma by immunohistochemistry on paraffin-embedded clinical samples. E2 was found to be highly expressed in the nuclei and cytoplasm of cells forming the intermediate and upper layers of cervical intraepithelial neoplasia (CIN). We could show that the expressions of E2 and p16(INK4a) (surrogate marker for oncogenic E7 expression) were exclusive in most of the cases, thus implying that E2 is not expressed together with high levels of E7. Moreover, we found that E2 is expressed in a subset of columnar cells adjacent to the CIN. We could show that expression of E2 is topologically distinct from the proliferation markers p63 and Ki67, whereas it coincides with the expression of cytokeratin K13, a marker of squamous cell differentiation. Expression of E2 also topologically coincides with episomal amplification of viral genomes in the upper layers of CIN1. These in vivo data thus validate previous assumptions of the crucial role of E2 in the early steps of HPV infection and of its negative link with expression of the viral E6 and E7 oncogenes.

  11. Alterations of MicroRNA Expression Patterns in Human Cervical Carcinoma Cells (Ca Ski) toward 1′S-1′-Acetoxychavicol Acetate and Cisplatin

    PubMed Central

    Phuah, Neoh Hun; In, Lionel LA; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah

    2013-01-01

    The aims of this study were to investigate the combined effects of a natural compound 1′S-1′-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski—low cisplatin sensitivity and HeLa—high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes. PMID:23012319

  12. Alterations of microRNA expression patterns in human cervical carcinoma cells (Ca Ski) toward 1'S-1'-acetoxychavicol acetate and cisplatin.

    PubMed

    Phuah, Neoh Hun; In, Lionel L A; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Nagoor, Noor Hasima

    2013-05-01

    The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.

  13. CD40L induces matrix-metalloproteinase-9 but not tissue inhibitor of metalloproteinases-1 in cervical carcinoma cells: imbalance between NF-kappaB and STAT3 activation.

    PubMed

    Smola-Hess, S; Schnitzler, R; Hadaschik, D; Smola, H; Mauch, C; Krieg, T; Pfister, H

    2001-07-15

    Matrix-metalloproteinases (MMPs) are essentially required for tumor cell invasion and metastasis. Production of precursor enzymes is regulated on transcriptional level, while activation of the pro-enzymes is tightly controlled by posttranscriptional mechanisms. The enzyme activity can be blocked by specific tissue inhibitors of MMPs (TIMPs). In cervical carcinomas strong up-regulation of the type IV collagenase MMP-9 had been demonstrated. We show that activation of CD40, a receptor highly expressed on cervical carcinomas, induces MMP-9 in cervical carcinoma cells, whereas TIMP-1 production inhibiting MMP-9 activity was not affected. This gene induction pattern corresponded to the differential activation of the transcription factor nuclear factor kappaB (NF-kappaB) regulating MMP-9, but not signal transducer and activator of transcription 3 (STAT3), which is involved in TIMP-1 gene regulation. Transient expression of the CD40-inducible NF-kappaB subunit p65 was sufficient for MMP-9 induction. Agents that suppressed CD40-mediated NF-kappaB activation also reduced MMP-9 induction, further supporting an important role of NF-kappaB in CD40-mediated MMP-9 induction. Our data suggest that CD40 expression in carcinoma cells might convert a CD40L-dependent immunological defense signal into a tumor-promoting signal. Selective CD40-mediated signaling through NF-kappaB but not STAT3 correlates to a shift of the balance between MMP-9 and TIMP-1 toward the protease.

  14. Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

    PubMed Central

    Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

    2016-01-01

    Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model. PMID:27807506

  15. Primary intraosseous squamous cell carcinoma arising in dentigerous cyst: Report of 2 cases and review of the literature

    PubMed Central

    Camps-Font, Octavi; López-Ramírez, Marta; Vidal-Bel, August

    2015-01-01

    Dentigerous cysts are one of the most common odontogenic cysts of the oral cavity. Odontogenic cysts can give rise to a variety of neoplasms. Carcinoma arising in a dentigerous cyst is extremely rare, with a review of literature showing near 30 cases. The present report describes 2 cases of primary intraosseous squamous cell carcinoma originated from a dentigerous cyst. The first one refers to a 57-year old female with a persistent lesion in the left retromolarregion and diagnosed with squamous cell carcinoma originated fromthe incomplete excision of the lower third molar follicle during its surgical extraction. The second case describes the case of an 18-year old male with an impacted upper canine with previous history of infection and swelling of the oral cavity. The histopathological study revealed the malignization of the follicle surrounding the dental crown. These two cases confirmed the importance of the histopathological study of all the tissue samples obtained from surgical procedures. Although the development of a malignant lesion from a dentigerous cyst is rare and its clinical-radiological features are apparently innocuous, this entity should be considered as a differential diagnosis. Key words:Dentigerous cyst, odontogenic cyst, squamous cell carcinoma, primary intraosseous squamous cell carcinoma, odontogenic carcinoma. PMID:26644846

  16. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China.

    PubMed

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin; Zhang, Guohong

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou. PMID:27610364

  17. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China

    PubMed Central

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou. PMID:27610364

  18. Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China

    PubMed Central

    Wang, Yuanyuan; Wang, Shaohong; Shen, Jinhui; Peng, Yanyan; Chen, Lechuan; Mai, Ruiqin

    2016-01-01

    Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou.

  19. Primary Lymphoepithelioma-Like Carcinoma of the Prostate Gland: A Review of the Literature.

    PubMed

    Venyo, Anthony Kodzo-Grey

    2016-01-01

    Background. Primary lymphoepithelioma-like carcinoma of the prostate gland (PLELCP) is rare with hardly any information on its diagnostic features and biological behaviour. Aim. To review the literature. Method. Various Internet data bases were searched. Literature Review. PLELCP is extremely rare and there are hardly any pictures of the tumour involving the prostate; hence it would appear that clinicians would need to use their knowledge of the microscopic and immunohistochemical characteristics of the tumour in the nasopharynx and urinary bladder as diagnostic aid. PLELCP on microscopy mimics nasopharyngeal LELC. The LELC component of the tumour is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. The stroma may be densely infiltrated by lymphoid cells admixed with some plasma cells and neutrophils and at times prominent infiltration of eosinophils. PLELCPs tend to have adenocarcinoma, either as the only pattern or with additional ductal components or adenosquamous carcinoma. PLELCPs stain positively with PSA, PSAP, AMACR/P504S, EMA, and cytokeratins AE1/AE3, 7, 8, and 20. There is no consensus on treatment of PLECP. The reported prognosis has been poor. Conclusions. PLELCPs should be entered into a multicenter trial to determine the biological behaviour and to find the best treatment option that would improve the prognosis. PMID:26881187

  20. Diagnostic Challenges in Primary Hepatocellular Carcinoma: Case Reports and Review of the Literature

    PubMed Central

    Pazgan-Simon, Monika; Serafinska, Sylwia; Janocha-Litwin, Justyna; Simon, Krzysztof; Zuwala-Jagiello, Jolanta

    2015-01-01

    Hepatocellular carcinoma is the fifth most common malignancy and the third leading mortality cause worldwide. It typically develops secondarily to liver cirrhosis, due to hepatitis B or C infection, alcohol abuse, metabolic disease, and so forth. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, which constitute diagnostic standards, the diagnosis of primary hepatocellular carcinoma (HCC) should be based on contrast-enhanced imaging. Lesion hyperenhancement should be observed throughout the arterial phase, followed by the washout during the venous phase. The diagnosis can also be based on the histopathological evaluation of liver biopsy specimen. Although the standards are clear, we often see patients with advanced HCC in clinical practice, who cannot be offered any effective treatment. Patients with chronic liver disease, presenting with inconclusive and changeable test results, constitute a separate problem. In such cases the diagnostic process is typically long-term and delayed. In this paper we present three case reports where the diagnosis could not be made promptly and the patients died as a result of a delayed diagnostic process. PMID:25922775

  1. Adenocarcinoma of the cervical stump

    SciTech Connect

    Goodman, H.M.; Niloff, J.M.; Buttlar, C.A.; Welch, W.R.; Marck, A.; Feuer, E.J.; Lahman, E.A.; Jenison, E.; Knapp, R.C. )

    1989-11-01

    Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

  2. Primary papillary carcinoma in thyroglossal cysts. Case reports and literature review.

    PubMed

    Chala, Andrés; Álvarez, Andrés; Sanabria, Álvaro; Gaitán, Alejandro

    2016-01-01

    The thyroglossal cyst can exceptionally appear as a primary cyst carcinoma. We discuss a series of 6 adult patients, assessed for long-lasting asymptomatic suprahyoid or lateral-to-larynx mass. The images showed a heterogeneous mass invading adjacent soft tissues. Fine needle aspiration biopsy did not contribute to diagnosis. We performed a Sistrunk procedure in all cases, 3 combined with total thyroidectomy and 1 with neck dissection. The postoperative course was favourable. No additional treatment was required, without evidence of recurrence in follow-up. The management is controversial due to the limited number of cases reported. Some classifications based on size and extent have been proposed to define the surgical treatment of such cysts.

  3. Primary signet ring cell carcinoma of the prostate treated by radical cystoprostatectomy and chemoradiotherapy

    PubMed Central

    Kim, Sun Wook; Kim, Woohyun; Cho, Yong-Hyun; Kim, Tae-Jung; Woo, Insuk; Sohn, Dong Wan

    2016-01-01

    Primary signet ring cell carcinoma (SRCC) of the prostate is very rare. Although SRCC is primarily found in the stomach and colon, it can also be found in the pancreas, breast, thyroid, bladder, and prostate. We recently diagnosed and treated a case of primary SRCC of the prostate. A 56-year-old Korean man was referred to our institution for evaluation of a one-month history of hematuria and recently identified bladder mass. Transurethral resection of the bladder tumour was performed and histological and immunohistochemical evaluation revealed a diagnosis of SRCC with tumour invading into the outer half of the deep muscularis propria. After three weeks, the patient had radical cystoprostatectomy with ileal conduit. Tumour involved both prostate and bladder, but the centre of the tumour was located in the prostate. Duodenoscopy and colon fibroscopy both indicated no evidence of tumour origin in the gastrointestinal (GI) tract. Overall, this tumour was regarded as primary SRCC of the prostate. Concurrent chemoradiotherapy (CCRT) using leucovorin and fluorouracil was initiated two months later. The patient eventually developed bone and liver metastases and died of hepatopathy.

  4. Primary fallopian tube carcinoma associated with ovulation induction; a case report.

    PubMed

    Deliveliotou, A; Hassiakos, D; Fotiou, S; Karvouni, E; Creatsas, G

    2008-01-01

    The potential relationship between ovulation induction and gynecological cancer has been raised recently. Primary fallopian tube carcinoma (PFTC) is an uncommon malignancy, not previously associated with fertility drugs use. We describe a case of a 38-year-old woman with primary infertility and a history of three ovulation inductions with gonadotropin-releasing hormone agonist and gonadotrophins, referred for treatment of bilateral ovarian cysts, which were discovered in the beginning of the last cycle. During laparotomy, bilateral adnexal masses were identified, presumed to be of ovarian origin, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and retroperitoneal lymph nodes sampling were performed. Histologic examination showed a primary right fallopian tube endometrioid adenocarcinoma and bilateral adnexal endometriosis. Surgery was followed by six cycles of combination chemotherapy using paclitaxel and carboplatin without significant complications. Although evidence of a direct causal link between ovarian stimulation and PFTC does not yet exist, this case highlights the importance for careful evaluation of all discovered adnexal masses in women undergoing ovulation induction treatment.

  5. Ipsilateral Irradiation for Oral and Oropharyngeal Carcinoma Treated With Primary Surgery and Postoperative Radiotherapy

    SciTech Connect

    Vergeer, Marije R.; Doornaert, Patricia; Jonkman, Anja; Kaanders, Johannes H.A.M.; Ende, Piet L.A. van den; Jong, Martin A. de; Leemans, C. Rene; Langendijk, Johannes A.

    2010-11-01

    Purpose: The purpose was to evaluate the contralateral nodal control (CLNC) in postoperative patients with oral and oropharyngeal cancer treated with ipsilateral irradiation of the neck and primary site. Late radiation-induced morbidity was also evaluated. Methods and Materials: The study included 123 patients with well-lateralized squamous cell carcinomas treated with surgery and unilateral postoperative irradiation. Most patients had tumors of the gingiva (41%) or buccal mucosa (21%). The majority of patients underwent surgery of the ipsilateral neck (n = 102 [83%]). The N classification was N0 in 73 cases (59%), N1 or N2a in 23 (19%), and N2b in 27 cases (22%). Results: Contralateral metastases developed in 7 patients (6%). The 5-year actuarial CLNC was 92%. The number of lymph node metastases was the only significant prognostic factor with regard to CLNC. The 5-year CLNC was 99% in N0 cases, 88% in N1 or N2a cases, and 73% in N2b cases (p = 0.008). Borderline significance (p = 0.06) was found for extranodal spread. Successful salvage could be performed in 71% of patients with contralateral metastases. The prevalence of Grade 2 or higher xerostomia was 2.6% at 5 years. Conclusions: Selected patients with oral or oropharyngeal carcinoma treated with primary surgery and postoperative ipsilateral radiotherapy have a very high CLNC with a high probability of successful salvage in case of contralateral metastases. However, bilateral irradiation should be applied in case of multiple lymph node metastases in the ipsilateral neck, particularly in the presence of extranodal spread. The incidence of radiation-induced morbidity is considerably lower as observed after bilateral irradiation.

  6. Detection of MYB Alterations and Other Immunohistochemical Markers in Primary Cutaneous Adenoid Cystic Carcinoma.

    PubMed

    North, Jeffrey P; McCalmont, Timothy H; Fehr, André; van Zante, Annemieke; Stenman, Göran; LeBoit, Philip E

    2015-10-01

    Adenoid cystic carcinoma (ACC) can arise in several organs, and prognosis is highly dependent on the primary tumor site. Primary cutaneous ACC has an excellent prognosis compared with salivary or lacrimal ACC. Activation of MYB by gene fusion or other mechanisms has been found in salivary, breast, and lacrimal ACCs but has not been described in cutaneous ACC. We analyzed the histopathologic and immunohistochemical features of 19 primary cutaneous ACCs, 2 periorbital ACCs, and 12 salivary gland ACCs and assessed for MYB activation in primary cutaneous ACC by immunohistochemistry and molecular methods. The presence of perineural invasion differed significantly among ACCs of various sites (83% salivary, 50% eyelid, 11% skin, P=0.0002). Over 90% of all ACCs were grade 1 or 2 and exhibited diffuse (>50%) positivity with CD117, SOX-10, and smooth muscle actin immunostains. CK15 and vimentin showed diffuse positivity in 36% and 57% of cutaneous ACCs, respectively, and were negative or only focally positive in all salivary ACCs (P=0.04 and 0.002). Six of the 11 cutaneous and periorbital ACCs tested with reverse transcriptase polymerase chain reaction and/or fluorescence in situ hybridization had MYB rearrangements including 2 cases that expressed MYB-NFIB fusion transcripts. Diffuse expression of MYB protein assessed by immunostaining was present in 8 of 9 cutaneous ACCs, including cases both with and without MYB rearrangements. These results indicate that cutaneous ACCs possess the same types of MYB alterations as ACCs of other anatomic sites. Vimentin and CK15 appear to have some discriminatory value in differentiating between primary cutaneous and salivary gland ACCs. PMID:26076064

  7. Primary Pulmonary Mucoepidermoid Carcinoma: Histopathological and Moleculargenetic Studies of 26 Cases

    PubMed Central

    Li, Ji; Li, Shanqing; Wu, Shafei; Liu, Yuanyuan; Luo, Yufeng; Cao, Jinling; Zeng, Xuan; Liang, Zhiyong

    2015-01-01

    cases were located in the lung. p63 and TTF-1 were positive in all cases (8/8), p40 was positive in 5 cases (5/8), and ALK was positive in 5 cases (5/8). No cases of MAML2 rearrangement were detected, but there were 5 cases of ALK rearrangement. Conclusions PMEC is a primary malignant pulmonary tumor with a relatively good prognosis that is historically characterized by the presence of mucous cells and a lack of keratinization. There are distinct differences between PMEC and MEC-like pulmonary carcinoma in tumor location preference, immunophenotype, and molecular genetics, and the differential diagnosis is critical due to the therapeutic and prognostic considerations. PMID:26575266

  8. Primary care provider practices and beliefs related to cervical cancer screening with the HPV test in Federally Qualified Health Centers

    PubMed Central

    Roland, K.B.; Benard, V.B.; Greek, A.; Hawkins, N.A.; Manninen, D.; Saraiya, M.

    2015-01-01

    Objective Cervical cancer screening using the human papillomavirus (HPV) test and Pap test together (co-testing) is an option for average-risk women ≥30 years of age. With normal co-test results, screening intervals can be extended. The study objective is to assess primary care provider practices, beliefs, facilitators and barriers to using the co-test and extending screening intervals among low-income women. Method Data were collected from 98 providers in 15 Federally Qualified Health Center (FQHC) clinics in Illinois between August 2009 and March 2010 using a cross-sectional survey. Results 39% of providers reported using the co-test, and 25% would recommend a three-year screening interval for women with normal co-test results. Providers perceived greater encouragement for co-testing than for extending screening intervals with a normal co-test result. Barriers to extending screening intervals included concerns about patients not returning annually for other screening tests (77%), patient concerns about missing cancer (62%), and liability (52%). Conclusion Among FQHC providers in Illinois, few administered the co-test for screening and recommended appropriate intervals, possibly due to concerns over loss to follow-up and liability. Education regarding harms of too-frequent screening and false positives may be necessary to balance barriers to extending screening intervals. PMID:23628517

  9. Protocol consisting of cisplatin, etoposide and irinotecan induced complete pathological remission of primary small cell carcinoma of the bladder.

    PubMed

    Kawahara, Takashi; Nishiyama, Hiroyuki; Yamamoto, Shingo; Kamoto, Toshiyuki; Ogawa, Osamu

    2006-09-01

    A 73-year-old man with primary small-cell carcinoma of the bladder was treated by radical cystectomy with neoadjuvant chemotherapy. Pathological complete remission was achieved by combination chemotherapy composed of cisplatin, etoposide and irinotecan. The patient is free of disease 19 months after surgery.

  10. Detection of cervical lymph node micrometastasis and isolated tumor cells in oral squamous cell carcinoma using immunohistochemistry and serial sectioning

    PubMed Central

    Dhawan, Isha; Sandhu, Simarpreet V; Bhandari, Rajat; Sood, Neena; Bhullar, Ramanpreet Kaur; Sethi, Neerja

    2016-01-01

    Introduction: Oral squamous cell carcinoma (OSCC) comprises one of the largest subsets of cancers with a tendency for regional metastasis. Nodal status is a key prognostic indicator in patients with OSCC, particularly with N0 neck. Occult metastasis in the form of micrometastasis (MM) and isolated tumor cells (ITCs), often goes undetected by routine hematoxylin and eosin (H&E) examination using 1–2 sections for analysis. This limitation could be overcome by combining serial sectioning (SS) with immunohistochemistry (IHC) for the detection of MM and ITC. Pan-cytokeratin (pan-CK) (AE1/AE3) is particularly a useful marker to detect these deposits as their presence has resulted in varied interpretations and different applications of the tumor-node-metastasis system. Objectives: The objective of the study was to identify a suitable method for detecting MM and ITC in lymph nodes (LNs) of OSCC by combining SS and IHC and to compare it with conventional H&E staining. Materials and Methods: This laboratory-based, prospective study was conducted on 133 LNs harnessed from ten patients treated with radical neck dissection for primary OSCC. The LNs were subjected to SS at 100 μm intervals. The sections were stained with routine H&E staining, pan-CK and analyzed for MM and ITC according to criteria laid by Hermanek et al. Statistical Analysis: The obtained data were subjected to statistical analysis using Chi-square test. Results: The application of combination of SS and IHC using pan-CK (AE1/AE3) in our study revealed the presence of MM and ITC in 2.25% of the LNs diagnosed as negative on routine H&E examination. The detection of these occult metastatic deposits resulted in upstaging of 33.33% of the patients. Conclusion: In the view of crucial role of occult LN metastasis in prognosis and survival of OSCC patients with N0 neck, diagnostic tools such as IHC staining, particularly with pan-CK (AE1/AE3), combined with SS should be preferred over conventional methods as they

  11. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.

    PubMed

    Dürst, M; Gissmann, L; Ikenberg, H; zur Hausen, H

    1983-06-01

    DNA from one biopsy sample of invasive cancer of the cervix contained sequences hybridizing with human papillomavirus (HPV) type 11 DNA only under nonstringent conditions. This DNA was molecularly cloned in lambda phage. Under stringent conditions of hybridization it cross-hybridized to a minor extent (less than 0.1%) with HPV types 10, 14, and 15 and showed no homology with DNA of other human HPV types. We therefore propose to designate it tentatively as HPV 16. HPV 16 DNA was used as a probe to test additional cancer biopsy samples from cervical, vulval, and penile cancer, as well as benign genital warts (condylomata acuminata) and cervical dysplasias for the presence of homologous sequences. In 61.1% (11/18) of cervical cancer samples from German patients sequences were found hybridizing with HPV 16 DNA under conditions of high stringency. In contrast, only 34.8% (8/23) of cancer biopsy samples from Kenya and Brazil revealed this DNA. Vulval and penile cancer biopsy samples hybridized to 28.6% (2/7) or 25% (1/4), respectively. Only 2 out of 33 condylomata acuminata contained HPV 16 DNA. Both positive tumors harbored in addition HPV 6 or HPV 11 DNA. The data thus indicate that HPV 16 DNA prevails in malignant tumors, rendering an accidental contamination with papillomavirus DNA from adjacent papillomas rather unlikely. The rare presence in benign genital papillomas in addition to common genital papillomaviruses suggests a dependence of HPV 16 replication on helper virus. PMID:6304740

  12. Nuclear Protein of the Testis Midline Carcinoma Masquerading as a Primary Mediastinal Seminoma

    PubMed Central

    Sayapina, Maria S.; Savelov, Nikita A.; Karseladze, Apollon I.; Bulanov, Anatoly A.; Tryakin, Alexey A.; Nosov, Dmitry A.; Garin, Avgust M.; Tjulandin, Sergey A.

    2016-01-01

    Nuclear protein of the testis (NUT) midline carcinomas are rare aggressive carcinomas characterized by chromosomal rearrangements that involve the gene encoding the NUT. This article reviews the clinicopathologic features and the differential diagnosis of these malignancies. PMID:27441078

  13. NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas

    PubMed Central

    Asch-Kendrick, Rebecca J.; Samols, Mark A.; Lilo, Mohammed T.; Subhawong, Andrea P.; Sharma, Rajni; Illei, Peter B.; Argani, Pedram; Cimino-Mathews, Ashley

    2015-01-01

    Aims NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status. Methods Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity. Results Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1–100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age. Conclusions This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas. PMID:24996432

  14. Head & Neck Squamous Cell Carcinoma of Unknown Primary: Neck Dissection and Radiotherapy or Definitive Radiotherapy

    PubMed Central

    Koukourakis, Georgios V.; Gutfeld, Orit; Prince, Mark E.; Bradford, Carol R.; Wolf, Gregory T.; McLean, Scott; Worden, Francis P.; Chepeha, Douglas B.; Schipper, Matthew J.; McHugh, Jonathan B.

    2014-01-01

    Background Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (ND+RT) or definitive RT both commonly used. We aimed to characterize HNCUP and retrospectively compare outcomes for patients treated with ND+RT versus definitive RT. Methods From 1994-2009, 41 HNCUP patients underwent either ND+RT (n=22) or definitive RT+ concurrent chemotherapy (n=19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test. Results There were no differences between patients treated with ND+RT and definitive RT in overall survival (OS), progression-free survival (PFS), or locoregional-relapse-free survival, freedom-from-locoregional failure, or freedom-from-distant failure. Among 17 ND+RT patients for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended towards improved OS (p=0.06)and PFS (p=0.15). Conclusions Neck dissection and post-op RT resulted in similar outcome as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers. PMID:23996575

  15. Developing in vitro models of human ductal carcinoma in situ from primary tissue explants.

    PubMed

    Brown, Daniel D; Dabbs, David J; Lee, Adrian V; McGuire, Kandace P; Ahrendt, Gretchen M; Bhargava, Rohit; Davidson, Nancy E; Brufsky, Adam M; Johnson, Ronald R; Oesterreich, Steffi; McAuliffe, Priscilla F

    2015-09-01

    Because there are currently no reliable predictors for progression of ductal carcinoma in situ (DCIS) to invasive disease, nearly all patients receive comprehensive therapy, leading to over-treatment in many cases. Few in vitro models for studying DCIS progression have been developed. We report here the successful culture and expansion of primary DCIS from surgical specimens using a conditional reprogramming protocol. Patients with percutaneous core-needle biopsy demonstrating DCIS were enrolled in a tissue banking protocol after informed consent was received. Fresh tissue was taken from lumpectomy or mastectomy specimens, mechanically and enzymatically dissociated, cultured in medium conditioned by irradiated mouse fibroblasts and supplemented with rho-associated protein kinase (ROCK) inhibitor, and characterized by immunocytochemistry. Out of 33 DCIS cases, 58% (19) were expanded for up to 2 months in culture, and 42% (14) were frozen immediately after mechanical dissociation for future growth. The cultures are almost exclusively composed of cytokeratin 8- and EpCAM-positive luminal and cytokeratin 14-, cytokeratin 5-, and p63-positive basal mammary epithelial cells, suggesting maintenance of heterogeneity in vitro. Furthermore, as assessed by luminal and basal marker expression, these cells retain their cellular identities both in the "conditionally reprogrammed" proliferative state and after conditioned media and ROCK inhibitor withdrawal. When grown to 100 % confluency, the cultures organize into luminal and basal layers as well as luminal compartments surrounded by basal cells. Primary cultures of DCIS derived directly from patient tissues can be generated and may serve as in vitro models for the study of DCIS.

  16. Primary Squamous Cell Carcinoma of the Remnant Stomach after Subtotal Gastrectomy

    PubMed Central

    Kim, Min Sung; Kim, Dong Hee; Park, Seulkee; You, Ji Young; Han, Joon Kil; Kim, Seong Hwan; Lee, Ho Jung

    2016-01-01

    Primary squamous cell carcinoma (SCC) of the stomach is a very rare disease. However, the pathogenesis, clinical characteristics, and prognosis of gastric SCC are controversial and remain to be elucidated. Herein, we report a case of primary gastric SCC of the remnant stomach after subtotal gastrectomy. A 65-year-old man was admitted to our hospital due to epigastric discomfort and dizziness. He had undergone subtotal gastrectomy 40 years previously for gastric ulcer perforation. Endoscopy revealed a normal esophagus and a large mass in the remnant stomach. Abdominal computed tomography revealed enhanced wall thickening of the anastomotic site and suspected metachronous gastric cancer. Endoscopic biopsy revealed SCC. Total gastrectomy was performed with Roux-en-Y esophagojejunostomy. A 10-cm tumor was located at the remnant stomach just proximal to the previous area of anastomosis. Pathologic examination showed well-differentiated SCC extended into the subserosa without lymph node involvement (T3N0M0). The patient received adjuvant systemic chemotherapy with 6 cycles of 5-FU and cisplatin regimen, and he is still alive at the 54-month follow-up. According to the treatment principles of gastric cancer, early detection and radical surgical resection can improve the prognosis. PMID:27433399

  17. Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

    PubMed

    Hoyo, C; Cousins, D S; Bisgrove, E Z; Gaines, M M; Schwingl, P J; Fortney, J A

    2004-12-01

    Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study. PMID:15816269

  18. Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

    PubMed

    Hoyo, C; Cousins, D S; Bisgrove, E Z; Gaines, M M; Schwingl, P J; Fortney, J A

    2004-12-01

    Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.

  19. Analysis of the Prevalence of HTLV-1 Proviral DNA in Cervical Smears and Carcinomas from HIV Positive and Negative Kenyan Women.

    PubMed

    He, Xiaotong; Maranga, Innocent O; Oliver, Anthony W; Gichangi, Peter; Hampson, Lynne; Hampson, Ian N

    2016-01-01

    The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some countries although its prevalence and relationship with other sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in genomic DNA extracted from liquid based cytology (LBC) cervical smears and invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus-positive (HIV+ve) and HIV-negative (HIV-ve) Kenyan women. Patient sociodemographic details were recorded by structured questionnaire and these data analysed with respect to HIV status, human papillomavirus (HPV) type (Papilocheck(®)) and cytology. This showed 22/113 (19.5%) of LBC's from HIV+ve patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV-ve women (p = 0.0002; odds ratio (OR) = 6.42 (2.07-26.56)). Only 1/37 (2.7%) of HIV+ve and none of the 44 HIV-ve ICC samples were positive for HTLV-1. There was also a significant correlation between HTLV-1 infection, numbers of sexual partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC samples was unexpected and the reasons for this are unclear. PMID:27608036

  20. Analysis of the Prevalence of HTLV-1 Proviral DNA in Cervical Smears and Carcinomas from HIV Positive and Negative Kenyan Women

    PubMed Central

    He, Xiaotong; Maranga, Innocent O.; Oliver, Anthony W.; Gichangi, Peter; Hampson, Lynne; Hampson, Ian N.

    2016-01-01

    The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some countries although its prevalence and relationship with other sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in genomic DNA extracted from liquid based cytology (LBC) cervical smears and invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus-positive (HIV+ve) and HIV-negative (HIV−ve) Kenyan women. Patient sociodemographic details were recorded by structured questionnaire and these data analysed with respect to HIV status, human papillomavirus (HPV) type (Papilocheck®) and cytology. This showed 22/113 (19.5%) of LBC’s from HIV+ve patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV−ve women (p = 0.0002; odds ratio (OR) = 6.42 (2.07–26.56)). Only 1/37 (2.7%) of HIV+ve and none of the 44 HIV−ve ICC samples were positive for HTLV-1. There was also a significant correlation between HTLV-1 infection, numbers of sexual partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC samples was unexpected and the reasons for this are unclear. PMID:27608036

  1. Primary Squamous Cell Carcinoma of Kidney Associated With Large Calculus in Non-functioning Kidney: A Case Report.

    PubMed

    Kumar, Sanjay; Tomar, Vinay; Yadav, Sher S; Udawat, Hema; Priyadarshi, Shivam; Vyas, Nachiket; Agarwal, Neeraj

    2016-09-01

    Primary squamous cell carcinoma (SCC) of renal pelvis is a rare neoplasm. A 75-year old male presented with history of chronic dull aching pain in left flank region for last 10-years with history of left pyelolithotomy about 30-years back. After proper workup, large calculus with heterogeneous density mass detected in nonfunctioning left kidney. After radical nephrectomy, histopathological examination revealed squamous cell carcinoma of renal pelvis. SCC should be suspected in a patient with long history of renal calculous and associated mass in non functioning kidney. PMID:27313983

  2. Extrauterine epithelioid trophoblastic tumors presenting as primary lung carcinomas: morphologic and immunohistochemical features to resolve a diagnostic dilemma.

    PubMed

    Lewin, Sharyn N; Aghajanian, Carol; Moreira, Andre L; Soslow, Robert A

    2009-12-01

    Our objective was to describe the clinicopathologic features of epithelioid trophoblastic tumors (ETTs) in a series of patients who presented with elevated beta-human chorionic gonadotrophin (hCG) levels and extrauterine lesions resembling primary lung carcinomas. Clinical and pathologic materials were reviewed and Shih and Kurman's diagnostic criteria were applied. Three parous women (38, 49, and 34 y of age) with elevated beta-hCG levels had nondiagnostic gynecologic evaluations, including negative dilation and curettage specimens. Imaging revealed isolated pulmonary lesions, 2 to 8.5 cm in size, resembling primary lung carcinomas. Two patients received multiagent chemotherapy consisting of etoposide, methotrexate, dactinomycin, alternating with cisplatin and etoposide, and all underwent pulmonary resection. Histologically, the cytologic features, epithelioid growth pattern, and hyaline-like material simulated the appearance of nonsmall cell lung carcinoma, but overall, the histologic features along with the immunophenotype supported classification as ETT. Follow-up hysterectomy specimens were histologically normal. All 3 patients are alive and well. The rarity of ETT and its resemblance to squamous and pleomorphic carcinomas of lung have led to diagnostic difficulties. When reproductive-age women present with elevated beta-hCG levels, a pulmonary lesion, and no apparent intrauterine disease, primary pulmonary ETT should be considered. Correlating clinical indices with specific morphologic and immunohistochemical features can ensure diagnostic accuracy and appropriate treatment for favorable outcomes.

  3. Endobronchial metastasis of a primary transitional-cell and signet-ring cell carcinoma of the urinary bladder.

    PubMed

    Cekmen, Nedim; Açiksöz, Sonay; Serdaroğlu, Hacer; Erdemli, Ozcan; Inan, Tansel

    2011-07-01

    Endobronchial metastasis is generally a late finding of primary tumor or may be determined before the diagnosis of primary tumor. We present a rare case of primary transitional and signet-ring cell carcinoma of the urinary bladder that occurred with malignant pleural effusion and endobronchial metastasis. A 71-year-old man complained of dyspnea and hematuria. He was admitted to the intensive care unit (ICU) with a prediagnosis of acute respiratory failure. He had decreased respiratory sounds and fine rales bilaterally at the lung bases. Respiratory failure worsened, and he was placed on mechanical ventilation. Radiograph and computed tomogram revealed bilateral effusion and metastatic nodules in the lung parenchyma. Subsequent abdominal computed tomogram revealed a mass in the urinary bladder, and transurethral biopsy indicated transitional epithelial carcinoma (modified Bergvist grade IIIB, and World Health Organization/International Society of Urological Pathology higher-grade urothelial papillary carcinoma) and signet-ring cell carcinoma, with lymphovascular invasion, consistent with the pathology findings. Our treatment plan was radical cysto-prostatectomy, followed by chemotherapy and radiotherapy, but because of his very poor medical status, the operation was not performed. On the 5th ICU day he died from severe respiratory failure, despite intensive supportive therapy. This case highlights the need to rule out malignancies in other organs in patients admitted with severe respiratory symptoms.

  4. Diagnosis and treatment in primary bladder small cell carcinoma: Literature review.

    PubMed

    Celik, Orcun; Ekin, Gokhan; Ipekci, Tumay; Budak, Salih; Ilbey, Yusuf Ozlem

    2016-03-01

    Small cell bladder carcinoma is a rare and frequently fatal disease. It can be distinguished from classical urothelial carcinoma microscopically and immunohistochemically. Small cell bladder carcinoma has histologically similar properties with other small cell carcinomas in other organs. It has a worse prognosis when compared to urothelial bladder cancer. Multimodal treatments are recommended although there is no widely accepted consensus regarding to the treatment algorithm because of its rarity. In this review, clinical properties and diagnosis of small cell bladder carcinoma, its histopathological and immunohistochemical properties and treatment modalities are examined. PMID:27072176

  5. Sonographic Evaluation of Cervical Lymphadenopathy; Comparison of Metastatic and Reactive Lymph Nodes in Patients With Head and Neck Squamous Cell Carcinoma Using Gray Scale and Doppler Techniques

    PubMed Central

    Ghafoori, Mahyar; Azizian, Amin; Pourrajabi, Zahra; Vaseghi, Hamed

    2015-01-01

    Background: Cervical lymphadenopathy could be seen in several pathologic processes. An accurate differentiation between these conditions is of utmost importance to select an appropriate therapy and assess the prognosis. Gray scale and Doppler are appropriate sonographic techniques for evaluating internal and external features of lymph nodes. Although, various criteria have been proposed to differentiate metastatic lymph nodes from benign ones, the most valuable and specific sonographic features are still under dispute. Objectives: The present study was designed to determine valuable sonographic features for differentiating metastasis from benign nodes using gray scale and Doppler sonography. Patients and Methods: A prospective diagnostic study was performed on 63 patients with head and neck squamous cell carcinoma (SCC) treated and referred to surgery clinic of Hazrat Rasoul Akram hospital from November 2010 to June 2012 with complaint of palpable cervical lymph node. All patients’ necks were scanned multidirectionally by gray-scale and Doppler techniques. After sonography, lymph nodes were biopsied and investigated to find out whether they were metastatic or reactive. Finally, demographic, sonographic and pathologic data were statistically analyzed by SPSS ver. 16 software using t-test, a nonparametric test and ROC analysis. Ninety five percent confidence interval was considered for all parameters. Results: The study included 41 males and 22 females with a mean age of 57.56 ± 13.79 years. The number of metastatic lymph nodes was 47, while the remaining 16 were reactive. There were significant differences in length (P = 0.037), width (P = 0.001), resistance index (P < 0.001), pulsatility index (P < 0.001) and systolic velocity (P < 0.001) of metastatic and reactive lymph nodes. Cut points for resistive and pulsatility indexes and systolic velocity were calculated as 0.695, 1.35 and 16.5, respectively. The most valuable factor for defining a lymph node as

  6. Mammographycally occult high grade ductal carcinoma in situ (DCIS) as second primary breast cancer, detected with MRI: a case report

    PubMed Central

    Zebic-Sinkovec, Marta; Kadivec, Maksimiljan; Podobnik, Gasper; Skof, Erik; Snoj, Marko

    2010-01-01

    Background Contralateral breast cancer (CLB) is the most common second primary breast cancer in patients diagnosed with breast cancer. The majority of patients harbouring CLB tumours develop the invasive disease. Almost all invasive carcinomas are believed to begin as ductal carcinoma in situ (DCIS) lesions. The sensitivity of MRI for DCIS is much higher than that of mammography. Case report We report the case of a woman who was treated with breast conserving therapy 10 years ago. At that time the invasive medullary carcinoma was diagnosed in the left breast. Ten years later mammographically occult DCIS was diagnosed with MRI-guided core biopsy in contralateral breast. Conclusions There might be a potential role of MRI screening as part of an annual follow-up for patients diagnosed with breast cancer. PMID:22933920

  7. Solid-type primary intraosseous squamous-cell carcinoma in the mandible: Report of a rare case.

    PubMed

    Alotaibi, Ohoud; Al-Zaher, Nabil; Alotaibi, Faiza; Khoja, Hatim; Qannam, Ahmed

    2016-09-01

    Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that has an exquisitely exclusive affection to the jawbone. It is defined as squamous cell carcinoma arising within the jaw and developing from residual odontogenic epithelium or from a preexisting odontogenic cyst or tumor. The solid-type of this tumor is a central jaw carcinoma arising de novo and has no initial connection with the oral mucosa. Herein, we report a case of solid-type PIOSCC involving the mandible in a 37-year-old male patient elucidating its histopathological and imaging findings. The patient underwent surgical resection followed by post-operative adjuvant radiotherapy. The close 2-year follow up of the patient revealed neither locoregional nor distant metastasis. PMID:26802621

  8. High-dose-rate Intracavitary Radiotherapy in the Management of Cervical Intraepithelial Neoplasia 3 and Carcinoma In Situ Presenting With Poor Histologic Factors After Undergoing Excisional Procedures

    SciTech Connect

    Kim, Yong Bae; Kim, Young Tae; Cho, Nam Hoon; Koom, Woong Sub; Kim, Sunghoon; Kim, Sang Wun; Nam, Eun Ji; Kim, Gwi Eon

    2012-09-01

    Purpose: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. Methods and Materials: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%). All patients were treated with HDR-ICR using Co{sup 60} or Ir{sup 192} at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. Results: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. Conclusions: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.

  9. The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas.

    PubMed

    Graflund, Marianne; Sorbe, B; Bryne, M; Karlsson, M

    2002-01-01

    This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients. PMID:11975674

  10. Primary squamous cell carcinoma of the rectum: An update and implications for treatment

    PubMed Central

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-01-01

    AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC’s are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the

  11. Antitumor activity of crude polysaccharides isolated from Solanum nigrum Linne on U14 cervical carcinoma bearing mice.

    PubMed

    Li, Jian; Li, Qingwang; Feng, Tao; Zhang, Tao; Li, Kun; Zhao, Rui; Han, Zengsheng; Gao, Dawei

    2007-09-01

    Solanum nigrum Linne (SNL) has been used in traditional Chinese medicine for centuries because of its diuretic and antipyretic effects. The present study examined the effect of the crude polysaccharides isolated from Solanum nigrum Linne (SNL-P) on tumor growth. SNL-P had a significant growth inhibition effect on cervical cancer (U14) of tumor-bearing mice. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl-2 and mutant p53 decreased dramatically in cervical cancer sections after oral administration of SNL-P for 12 days. Moreover, SNL-P treatment decreased the level of blood serum TNF-alpha. These results indicated that the tumor growth inhibition of SNL-P administration might correlate with the reduction of TNF-alpha level of blood serum, which resulted in a massive necrosis in tumor tissues and the up-regulation of Bax and down-regulation of Bcl-2 and mutant p53 gene expression, which triggered apoptosis in tumor cells. These findings demonstrated that the SNL-P is a potential antitumor agent. PMID:17486683

  12. Digital-Direct-RT-PCR: a sensitive and specific method for quantification of CTC in patients with cervical carcinoma

    PubMed Central

    Pfitzner, Claudia; Schröder, Isabel; Scheungraber, Cornelia; Dogan, Askin; Runnebaum, Ingo Bernhard; Dürst, Matthias; Häfner, Norman

    2014-01-01

    The detection of circulating tumour cells (CTC) in cancer patients may be useful for therapy monitoring and prediction of relapse. A sensitive assay based on HPV-oncogene transcripts which are highly specific for cervical cancer cells was established. The Digital-Direct-RT-PCR (DD-RT-PCR) combines Ficoll-separation, ThinPrep-fixation and one-step RT-PCR in a low-throughput digital-PCR format enabling the direct analysis and detection of individual CTC without RNA isolation. Experimental samples demonstrated a sensitivity of one HPV-positive cell in 500,000 HPV-negative cells. Spike-in experiments with down to 5 HPV-positive cells per millilitre EDTA-blood resulted in concordant positive results by PCR and immunocytochemistry. Blood samples from 3 of 10 CxCa patients each contained a single HPV-oncogene transcript expressing CTC among 5 to 15*105 MNBC. Only 1 of 7 patients with local but 2 of 3 women with systemic disease had CTC. This highly sensitive DD-RT-PCR for the detection of CTC may also be applied to other tumour entities which express tumour-specific transcripts. Abbreviations: CTC – circulating tumour cells, CxCa – cervical cancer, DD-RT-PCR – Digital-Direct Reverse Transcriptase PCR, HPV – Human Papilloma Virus, MNBC – mononuclear blood cells, ICC – immunocytochemistry. PMID:24496006

  13. PTEN as a molecular marker to distinguish metastatic from primary synchronous endometrioid carcinomas of the ovary and uterus.

    PubMed

    Ricci, Romeo; Komminoth, Paul; Bannwart, Fridolin; Torhorst, Joachim; Wight, Edward; Heitz, Philipp U; Caduff, Rosmarie F

    2003-06-01

    The distinction between two primary carcinomas on the one hand and a metastatic disease on the other hand in patients suffering from synchronous endometrioid carcinomas of the uterus and ovary is difficult. Exclusive histopathologic analysis appears to be insufficient and sometimes misleading. The tumor suppressor PTEN was found to be important in early neoplastic transformation in endometrioid carcinomas of the uterus. In this study, we screened synchronous endometrioid carcinomas of the uterus and ovary of 10 patients for loss of heterozygosity using seven different microsatellite markers at 10q23.3 and for mutations in the entire coding region of PTEN. Point mutations or microdeletions/insertions were found in six patients. Allelic loss at 10q23.3 was detected in eight patients. Based on conventional histology, a metastatic disease was diagnosed in seven patients and a concomitant uterine and ovarian carcinoma in three patients. After molecular analysis, the histopathologic diagnosis of three patients had to be revised. Histopathology represents the standard method to process tumor specimens from these patients. Nevertheless, mutation screen for PTEN and LOH analysis at 10q23.3 provide helpful genetic tools to establish a correct final diagnosis, which is important in view of prognosis and therapeutic implications.

  14. Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review.

    PubMed

    Hellquist, Henrik; Skálová, Alena; Barnes, Leon; Cardesa, Antonio; Thompson, Lester D R; Triantafyllou, Asterios; Williams, Michelle D; Devaney, Kenneth O; Gnepp, Douglas R; Bishop, Justin A; Wenig, Bruce M; Suárez, Carlos; Rodrigo, Juan P; Coca-Pelaz, Andrés; Strojan, Primož; Shah, Jatin P; Hamoir, Marc; Bradley, Patrick J; Silver, Carl E; Slootweg, Pieter J; Vander Poorten, Vincent; Teymoortash, Afshin; Medina, Jesus E; Robbins, K Thomas; Pitman, Karen T; Kowalski, Luiz P; de Bree, Remco; Mendenhall, William M; Eloy, Jean Anderson; Takes, Robert P; Rinaldo, Alessandra; Ferlito, Alfio

    2016-03-01

    Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.

  15. Development and evaluation of an anchorage-independent agar-based clonal assay for human primary breast carcinoma cells

    SciTech Connect

    Besch, G.J.

    1985-01-01

    The development and evaluation of an anchorage-independent clonal cytotoxic assay for primary human breast carcinoma cells is described in this thesis. This assay was developed in three stages which include: (1) the optimization of the production of a monodispersed cell suspension from solid breast carcinomas, (2) the systematic development of a growth medium for the clonal growth of these cells, and (3) the adaptation of these methods for use in the quantitation of cytotoxicity. The results of these studies indicated that hydrocortisone, fetal bovine serum and red blood cells stimulated the clonal growth of breast carcinoma cells. The optimal concentrations of these three factors were simultaneously determined using response surface methodology. These culture conditions were then used to develop radiation-cytotoxicity assays for both primary and recurrent breast carcinomas. The methodology developed and evaluated in this thesis may be useful to: (1) study the biology and radiobiology of human breast cancer, (2) customize the treatment of individual breast cancer patients, and (3) identify and/or develop new drugs and/or other treatment modalities for breast cancer.

  16. An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using Podophyllum hexandrum on human cervical carcinoma cells.

    PubMed

    Jeyaraj, Murugaraj; Rajesh, Manoharan; Arun, Renganathan; MubarakAli, Davoodbasha; Sathishkumar, Gnanasekar; Sivanandhan, Ganeshan; Dev, Gnanajothi Kapil; Manickavasagam, Markandan; Premkumar, Kumpati; Thajuddin, Nooruddin; Ganapathi, Andy

    2013-02-01

    Now-a-days synthesis and characterization of silver nanoparticles (AgNPs) through biological entity is quite interesting to employ AgNPs for various biomedical applications in general and treatment of cancer in particular. This paper presents the green synthesis of AgNPs using leaf extract of Podophyllum hexandrum Royle and optimized with various parameters such as pH, temperature, reaction time, volume of extract and metal ion concentration for synthesis of AgNPs. TEM, XRD and FTIR were adopted for characterization. The synthesized nanoparticles were found to be spherical shaped with average size of 14 nm. Effects of AgNPs were analyzed against human cervical carcinoma cells by MTT Assay, quantification of ROS, RT-PCR and western blotting techniques. The overall result indicates that AgNPs can selectively inhibit the cellular mechanism of HeLa by DNA damage and caspase mediated cell death. This biological procedure for synthesis of AgNPs and selective inhibition of cancerous cells gives an alternative avenue to treat human cancer effectively.

  17. Expression of cancer stem markers could be influenced by silencing of p16 gene in HeLa cervical carcinoma cells.

    PubMed

    Wu, H; Zhang, J; Shi, H

    2016-01-01

    Effect of the tumor suppression gene p16 on the biological characteristics of HeLa cervical carcinoma cells was explored. The expression of p16 protein was increased in HeLa tumor sphere cells, and no significant difference in tumor spheres from the first to the fourth passages. Compared with those of parental HeLa cells, the proportion of CD44+/CD24- and ABCG2+ cells increased significantly in tumor spheres. However after the cells were silenced by the p16-sh289 vector, expression of P16 protein and the cell number of CD44+/CD24- and ABCG2+ decreased. Moreover, HeLa cells with p16 gene silencing showed decreased abilities of sphere formation and matrigel invasion. More HeLa cells with p16 gene silence were needed for tumor formation in nude mice. Tumor size and weight in mouse model established with p16 gene silenced HeLa cells were less than those with HeLa parental cell model. The present results indicate that silencing of the p16 gene inhibits expression of cancer stem cell markers and tumorigenic ability of HeLa cells.

  18. Adjuvant Therapeutic Modalities in Primary Small Cell Carcinoma of Esophagus Patients

    PubMed Central

    Zou, Bingwen; Li, Tao; Zhou, Qiang; Ma, Daiyuan; Chen, Yongshun; Huang, Meijuan; Peng, Feng; Xu, Yong; Zhu, Jiang; Ding, Zhenyu; Zhou, Lin; Wang, Jin; Ren, Li; Yu, Min; Gong, Youling; Li, Yanying; Chen, Longqi; Lu, You

    2016-01-01

    Abstract To evaluate the treatment pattern and survival of patients receiving radical resection for primary small cell carcinoma of the esophagus (PSCCE). This retrospective study included 150 patients who received radical resection of PSCCE. Data were retrieved from 4 centers in Western China. Thirty-nine of 150 patients received postoperative chemo-radiotherapy, 62 received postoperative chemotherapy, and 49 received radical resection only. The median radiation dosage was 50 Gy. The chemotherapeutic regimen was platinum-based and lasted for 2 to 6 cycles (median, 3). Median disease-free survival (mDFS) and overall survival (mOS) were 12.0 and 18.3 months, respectively. Subgroup analysis revealed that postoperative therapy did not improve survival in limited stage I (LSI) disease, whereas postoperative chemotherapy improved survival in limited stage II (LSII) disease. Relative to chemotherapy alone, chemoradiotherapy did not improve survival in patients with completely resected LSII disease. A multivariate analysis indicated an association of no postoperative chemotherapy with shorter DFS (P = 0.050) and OS (P = 0.010). Higher lymph node stage and length of disease longer than 3 cm were poor prognostic factors for both DFS and OS. Adjuvant chemotherapy improves survival in PSCCE patients with completely resected LSII disease. Adjuvant treatment with postoperative chemotherapy alone or postoperative chemo-radiotherapy does not increase survival in completely resected LSI disease. PMID:27124057

  19. Anti-human AFP variant monoclonal antibody in radioimmunodetection of primary hepatocellular carcinoma

    PubMed Central

    Liu, Yang; Wu, Meng-Chao; Chen, Han; Zhang, Bai-He; Qian, Guang-Xiang; Pan, Wen-Zhou; Qiang, Mei-Yu

    1997-01-01

    AIM: To investigate the affinity of AFP-R-LCA monoclonal antibody (AFP-R-LCA McAb) for AFP-positive primary hepatocellular carcinoma (HCC) cells. METHODS: AFP-R-LCA McAb was labeled by 131I. Eleven cases of HCC with AFP positivity, 6 with AFP negativity, and 4 with hepatitis B-related cirrhosis were investigated by radioimmunodetection. RESULTS: The 131I-AFP-R-LCA McAb immunoreacted with 9 of the HCC AFP-positive cases (9/11), but with none of the 6 AFP negative HCC cases or of the 4 cirrhosis patients. 131I-AFP-R-LCA McAb at a small dose (7.4 × 107 Bq/300 μg) was associated with no side effects as determined by the liver function test, prothrombin time (Pt) test and thyroid gland function test (P > 0.05). Two cases of AFP-positive HCC were not imaged because of large tumor size (diameter > 10 cm) and higher AFP concentration in serum (20000 μg/L). CONCLUSION: AFP-R-LCA McAb has a strong and special affinity to AFP-positive HCC cells and may be useful as a carrier for radioimmunodetection and radioimmunotherapy. PMID:27053873

  20. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival.

    PubMed

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60-4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  1. Primary mucinous adenocarcinoma of the renal pelvis with carcinoma in situ in the ureter.

    PubMed

    Abbas, Mahmoud; Kramer, Mario W; Spieker, Tilmann; Herrman, Thomas R W; Merseburger, Axel S; Müller, Klaus-Michael; Kuczyk, Marcus A; Becker, Jan U; Kreipe, Hans-Heinrich

    2014-03-01

    Primary epithelial tumor of the renal pelvis is rare and only 100 cases are reported in the literature [1]. Histological examination of the tumor showed glands, cysts, and papillae lined by pseudostratified columnar epithelium with hyperchromatic nuclei. Scattered signet ring-type cells were also seen floating in large pools of extracellular mucin. Sections from the ureter showed a component of adenocarcinoma in situ. No invasive tumor was identified in ureteric tissue. One case was reported with carcinoma in situ of the ureter (2). Immunohistochemically: The tumor showed positivity for CK7, CK20, CK8/18, GATA-3, MSH-2, MSH-6, MLH-1, Ber-EP4, and S-100-P with focal positivity for CDX-2, weak positivity for PMS-2 and negativity in TTF-1 and Her-2. Molecular pathological analysis revealed microsatellite stability and without mutation in K-ras-gene. Thus, a diagnosis of mucinous adenocarcinoma of the renal pelvis with in situ adenocarcinoma of the ureter was made. PMID:24565683

  2. Recombinant soluble gp130 protein reduces DEN-induced primary hepatocellular carcinoma in mice

    PubMed Central

    Hong, Jing; Wang, Hang; Shen, Guoying; Lin, Da; Lin, Yanxue; Ye, Nanhui; Guo, Yashan; Li, Qiaoling; Ye, Nanhui; Deng, Chengjun; Meng, Chun

    2016-01-01

    IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Soluble gp130 (sgp130) is known to be a natural inhibitor of the trans-signaling pathway. In the present study, our goal was to investigate whether recombinant sgp130 could suppress the initiation and progression of HCC in mouse models. Our results demonstrate that sgp130 induced an apoptosis of HepG2 cells and inhibited the clonogenicity of HepG2 in vitro. Moreover, the IL-6 trans-signaling pathway is significantly suppressed by sgp130 as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. In the DEN-induced HCC mouse model, intravenous injection of sgp130 attenuated hepatic fibrosis at 16 weeks and reduced the initiation and progression of primary HCC at 36 weeks. Furthermore, our results also demonstrate that intravenous administration of sgp130 significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice. PMID:27080032

  3. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival

    PubMed Central

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60–4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  4. Pre-operative mediastinal evaluation in primary bronchial carcinoma--a review of staging investigations.

    PubMed Central

    Elliott, J. A.

    1984-01-01

    A review of staging investigations in the preoperative evaluation of mediastinal involvement in primary bronchial carcinoma is presented. The following conclusions are offered as guidelines for the use of mediastinal staging procedures in clinical practice: Surgical staging methods have the over-riding advantage of superior specificity over indirect imaging techniques. Where 67Ga-imaging or CT scanning are not available, routine pre-operative mediastinoscopy or, when appropriate, mediastinotomy will identify most patients with non-resectable disease but this approach entails a high proportion of true negative examinations. Radioisotope ventilation and perfusion lung imaging has no place in the pre-operative staging of lung cancer. Where the techniques are available, 67Ga-imaging and CT scanning have a use in selecting patients for mediastinal exploration. A negative mediastinal 67Ga scan or a negative CT examination suggest that mediastinal exploration will be unrewarding in the vast majority of cases and may be omitted prior to thoracotomy. A positive mediastinal 67Ga scan or the demonstration of abnormal mediastinal nodes by CT is an indication for mediastinal exploration which, if negative should be followed by thoracotomy. PMID:6369288

  5. Clinicopathological Characteristics, Treatment, and Prognosis of 21 Patients with Primary Gastric Squamous Cell Carcinoma

    PubMed Central

    Xu, Feng; Cao, Yidan; Gu, Xingting; Wan, Yuming

    2016-01-01

    We performed a retrospective analysis of 21 patients with primary gastric squamous cell carcinoma (PGSCC) who were admitted to our hospital from October 2008 to October 2014. The median age was 67 years and male predominance was observed, the most common tumor locations were the upper third of the stomach, most of the clinical manifestations were identical to those of other types of gastric tumors, and the tumor cells had positive immunoreactivity for p63 and CK5/6. In terms of treatments, surgery (R0 resection) is the main treatment; the effect of other treatments is unclear. The median survival time for the surgery group and nonsurgery group was 46 and 4.5 months, respectively. Probably due to limited number of cases, no significant difference in median survival time was observed between the surgery alone group and the surgery plus adjuvant therapy group (46 versus 51 months, P = 0.310). A standard chemotherapy regimen for this disease has not yet been established; the choice of its chemotherapy regimens tends to follow the principle of the treatment of gastric adenocarcinoma or esophageal cancer. PGSCC generally had a poor prognosis, and early detection, early diagnosis, and early surgical treatment are beneficial to patients. PMID:27478431

  6. Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients

    PubMed Central

    Peng, Hao; Chen, Lei; Tang, Ling-Long; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared. PMID:26934649

  7. A rare case of primary peripheral epithelial myoepithelial carcinoma of lung

    PubMed Central

    Shen, Cheng; Wang, Xin; Che, Guowei

    2016-01-01

    Abstract Background: Primary salivary gland–type tumors of lung are rare. Epithelial–myoepithelial carcinoma (EMC) of the lung is a minor salivary gland–type tumor subtype. Methods: We report a very rare case of EMC located in the peripheral left lower lobe that was diagnosed in a 58-year-old man and this is the first study in which we summarize all the patients with primary peripheral lung EMC concerned with the clinical features. Informed consent was obtained from the patient. Results: Chest computed tomography displayed an anomalous soft tissue mass with slightly lobular borders in the peripheral segment of the left lower lobe and closed to the visceral pleura. The surgery was performed by using video-assisted thoracic surgery. Grossly, the tumor was solitary, well-circumscribed, and unencapsulated endobronchial lesion. A microscopic examination revealed that it was circumscribed, although the tumor borders may show single cells or clusters of cells proliferating away from the main tumor mass. The inner tubular layer showed epithelial cell characteristics, whereas the outer layer exhibited myoepithelial cell characteristics. Immunostaining for P40, P63, and cytokeratin 5/6 was positive. However, the anaplastic lymphoma kinase-V, thyroid transcription factor-1, synaptophysin, chromogranin A and napsin A were negative. Conclusions: Literature review showed that most of patients with peripheral EMC were asymptomatic. Computed tomography and magnetic resonance imaging scans are able to indicate the presence of peripheral EMC. Pathological analysis is an effective method to clarify the diagnosis. Surgery is a regular treatment method. To facilitate the preoperative diagnosis and avoid the misdiagnosis of such a rare disease, more cases will need to be reported. PMID:27583848

  8. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma

    PubMed Central

    Liu, Hui; Li, Peng; Zhai, Yun; Qu, Chun-Feng; Zhang, Li-Jie; Tan, Yu-Fen; Li, Ning; Ding, Hui-Guo

    2010-01-01

    AIM: To evaluate the diagnostic value of glypican-3 (GPC3) in serum and liver for primary hepatocellular carcinoma (HCC). METHODS: Serum levels of GPC3 and α-fetoprotein (AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis. Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining. RESULTS: When the cut-off value of serum GPC3 was set at 300 ng/L, its sensitivity and specificity for HCC were 47.0% and 93.5%, respectively. Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system, the serum GPC3 level was higher than 300 ng/L in 50% (7/14) patients, the serum AFP level was not ≥ 400 μg/L in any patient. Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC. The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors. Among the 58 HCC patients, the GPC3 was expressed in 100% (28/28) patients with their serum AFP level ≥ 400 μg/L, and in 90% (27/30) patients with their AFP level < 400 μg/L, respectively. The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples. AFP positive HCC cells were only found in 1 out of the 58 HCC patients. CONCLUSION: GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC. Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells. PMID:20845507

  9. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

    PubMed Central

    Baine, Marina K.; Turcu, Gabriela; Zito, Christopher R.; Adeniran, Adebowale J.; Camp, Robert L.; Chen, Lieping

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. PMID:26317902

  10. Poor Prognosis Associated With Human Papillomavirus α7 Genotypes in Cervical Carcinoma Cannot Be Explained by Intrinsic Radiosensitivity

    SciTech Connect

    Hall, John S.; Iype, Rohan; Armenoult, Lucile S.C.; Taylor, Janet; Miller, Crispin J.; Davidson, Susan; Sanjose, Silvia de; Bosch, Xavier; Stern, Peter L.; West, Catharine M.L.

    2013-04-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity. Methods and Materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA{sub 25}) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays. Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14). Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.

  11. Cervical Laminoplasty

    MedlinePlus

    ... Treatments for Spinal Pain Surgical Options Anterior Cervical Fusion Artificial Disc Replacement Bone Graft Alternatives Bone Morphogenetic ... Discectomy Percutaneous Vertebral Augmentation Posterior Cervical Foraminotomy Spinal Fusion ... Medicine Cervical Laminoplasty What is ...

  12. DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase

    PubMed Central

    Srinivas, Kalanghad Puthankalam; Viji, Remadevi; Dan, Vipin Mohan; Sajitha, Indira Sukumaran; Prakash, Rajappan; Rahul, Puthan Valappil; Santhoshkumar, Thankayyan R.; Lakshmi, Subhadra; Pillai, Madhavan Radhakrishna

    2016-01-01

    DEPTOR is an endogenous inhibitor of mTOR complexes, de-regulated in cancers. The present study reveals a vital role for DEPTOR in survival of cervical squamous cell carcinoma (SCC). DEPTOR was found to be overexpressed in both cervical SCC cells and tissues and it's silencing in cervical SCC cells induced apoptosis, mainly by up-regulation of p38 MAPK and by inhibiting PI3K/AKT pathway via a feed-back inhibition from mTORC1-S6K. DEPTOR silencing resulted in reduced expression of the nitric oxide synthases iNOS and eNOS, as well as increased activation of ERK1/2 and p38 MAP kinases. Activation of AKT signaling by overexpression of constitutively active-AKT (CA-AKT) failed to overcome the apoptosis caused by DEPTOR silencing. Similarly pharmacological inhibition of ERK also failed to control apoptosis. However pharmacological inhibition of p38 MAPK rescued the cells from apoptosis, indicating the major role of p38 MAPK in cell death induced by DEPTOR silencing. DEPTOR was also found to regulate ERK1/2 in an AKT dependent manner. DEPTOR knockdown induced cell death in SiHa cells overexpressing the anti-apoptotic Bcl-2 and Bcl-xL, indicating strong survival role of DEPTOR in these cells. DEPTOR overexpression activated PI3K/AKT by relieving the negative feed-back inhibition from mTORC1-S6K. DEPTOR regulation was also observed to be independent of HPV E6/E7 oncoproteins, but it might be a molecular co-factor contributing to cervical carcinogenesis. In summary, DEPTOR is found to promote survival of cervical SCC cells and its reduction induced apoptosis via differential effects on PI3K/AKT and p38 MAPK and can be a potential target in cervical SCC. PMID:26992219

  13. Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit S.; Surude, Ravindra G.; Pawar, Vinay B.; Udgirkar, Suhas; Rathi, Pravin M.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making. PMID:27721663

  14. Testicular Signet-Ring Cell Metastasis from a Carcinoma of Unknown Primary Site: A Case Report and Literature Review

    PubMed Central

    Kollas, Aristomenes; Zarkavelis, George; Goussia, Anna; Kafantari, Aikaterini; Batistatou, Anna; Sintou, Eva

    2016-01-01

    Signet-ring cell carcinoma is a highly malignant adenocarcinoma consisting of cells characterized as cytoplasmic vacuoles filled with mucin. The most common primary location of this type of cancer is the stomach, but it may also be found in other organs such as prostate, testis, bladder, ovaries, or colon. To date, metastatic signet-ring cell carcinoma of unknown primary (CUP) site to the testis is an extremely rare entity in daily practice. Reviewing the literature, we have been able to detect only three cases of testicular metastases from CUP, two with histological diagnosis of a signet-ring cell carcinoma and one with an adenocarcinoma. In this short paper, we report a case of a 56-year-old man who presented to our Department with testicular mass and ascites. Following a standard diagnostic approach no primary tumor could be identified. CUP was the final clinical diagnosis, histologically characterized as poorly differentiated adenocarcinoma with signet-ring cells involving the peritoneum and the testicular structures. PMID:27504206

  15. Testicular Signet-Ring Cell Metastasis from a Carcinoma of Unknown Primary Site: A Case Report and Literature Review.

    PubMed

    Kollas, Aristomenes; Zarkavelis, George; Goussia, Anna; Kafantari, Aikaterini; Batistatou, Anna; Evangelou, Zoi; Sintou, Eva; Pavlidis, Nicholas

    2016-01-01

    Signet-ring cell carcinoma is a highly malignant adenocarcinoma consisting of cells characterized as cytoplasmic vacuoles filled with mucin. The most common primary location of this type of cancer is the stomach, but it may also be found in other organs such as prostate, testis, bladder, ovaries, or colon. To date, metastatic signet-ring cell carcinoma of unknown primary (CUP) site to the testis is an extremely rare entity in daily practice. Reviewing the literature, we have been able to detect only three cases of testicular metastases from CUP, two with histological diagnosis of a signet-ring cell carcinoma and one with an adenocarcinoma. In this short paper, we report a case of a 56-year-old man who presented to our Department with testicular mass and ascites. Following a standard diagnostic approach no primary tumor could be identified. CUP was the final clinical diagnosis, histologically characterized as poorly differentiated adenocarcinoma with signet-ring cells involving the peritoneum and the testicular structures. PMID:27504206

  16. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion.

    PubMed

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Michael Tuttle, R; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-09-01

    ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47-72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6-NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long

  17. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

    PubMed Central

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Tuttle, R Michael; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-01-01

    ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated

  18. Cervical cancer.

    PubMed

    Shepherd, John H

    2012-06-01

    Standard treatment for invasive cervical cancer involves either radical surgery or radiotherapy. Childbearing is therefore impossible after either of these treatments. A fertility-sparing option, however, by radical trachelectomy has been shown to be effective, provided that strict criteria for selection are followed. Fertility rates are high, whereas recurrence is low, indicating that a more conservative approach to dealing with early small cervical tumours is feasible. Careful preoperative assessment by magnetic resonance imaging scans allows accurate measurement of the tumour with precise definition to plan surgery. This will ensure an adequate clear margin by wide excision of the tumour excising the cervix by radical vaginal trachelectomy with surrounding para-cervical and upper vaginal tissues. An isthmic cerclage is inserted to provide competence at the level of the internal orifice. A primary vagino-isthmic anastomosis is conducted to restore continuity of the lower genital tract. Subsequent pregnancies require careful monitoring in view of the high risk of spontaneous premature rupture of the membranes. Delivery by classical caesarean section is necessary at the onset of labour or electively before term. Over 1100 such procedures have been carried out vaginally or abdominally, resulting in 240 live births. Radical vaginal trachelectomy with a laparoscopic pelvic-node dissection offers the least morbid and invasive route for surgery, provided that adequate surgical skills have been obtained. PMID:22353492

  19. Carcinoma of the oral cavity: on the prognostic significance of the primary tumour site (by levels and areas).

    PubMed

    Fries, R; Platz, H; Wagner, R; Strickler, A; Grabner, H; Kränzl, B; Krekeler, G; Kriens, O; Leijhanec, J; Mennert, H; Scharf, F; Schroll, K; Schulz, P; Vinek, G; Waldhart, E; Wepner, F; Zisser, G

    1979-02-01

    The prognostic significance of primary tumour site in carcinomas of the oral cavity was investigated in a series of 585 cases. For the subsamples (levels and areas of oral cavity) studied, the numerical distribution of TNM categories, life tables and life table comparisons were computed. This produced the following results: Given an identical extension and analogous metastazising rate, there is no computationally demonstrable difference in prognosis between primary tumours sited at different levels and areas of the oral cavity. The exception are the T1Nx categories, for which a difference exists between precanine and retromolar sites. These results should be re-examined on the basis of a larger series. PMID:285996

  20. A Functional Polymorphism in the Promoter of MiR-143/145 Is Associated With the Risk of Cervical Squamous Cell Carcinoma in Chinese Women

    PubMed Central

    Liang, Yundan; Sun, Ruifen; Li, Lijuan; Yuan, Fang; Liang, Weibo; Wang, Li; Nie, Xinwen; Chen, Peng; Zhang, Lin; Gao, Linbo

    2015-01-01

    Abstract MiR-143/145 is down-regulated in cervical cancer, which may serve as a tumor suppressor by targeting KRAS and Ras-responsive element-binding protein (RREB1). Activated KRAS leads to down-regulation of miR-143/145 transcription in a RREB1-dependent manner, establishing a miR-143/145-KRAS-RREB1 feedback loop. A polymorphism rs4705343C/T in the promoter of miR-143/145 might influence the binding of TATA-binding protein. We hypothesized that the miR-143/145 rs4705343 and KRAS rs712 may be related to the occurrence of cervical squamous cell carcinoma (CSCC). In this study, we genotyped the 2 polymorphisms in 415 patients with CSCC and 504 controls using polymerase chain reaction–restriction fragment length polymorphism. The promoter activities were measured by the Dual-Luciferase Reporter Assay System. We found that the rs4705343TC genotype was associated with an increased risk of CSCC (adjusted odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.05–1.80). The significantly increased association was also observed in a dominant genetic model (adjusted OR = 1.32; 95% CI, 1.01–1.72). Combined analysis showed that individuals carrying the genotypes of rs4705343 TC/CC and rs712GT/TT had a 1.47-fold increased risk of CSCC (adjusted OR = 1.47; 95% CI, 1.01–2.15). By using multifactor dimensionality reduction software method, we identified a significant interaction between the miR-143/145 rs4705343 and KRAS rs712. Dual-Luciferase Reporter Assay showed that the luciferase activity was significantly lower in cells transfected with the rs4705343C allele than that of the rs4705343T allele. These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of CSCC in Chinese women. PMID:26252302

  1. A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study

    PubMed Central

    Clayton, Erica Fan; Furth, Emma Elizabeth; Ziober, Amy; Xu, Theodore; Yao, Yuan; Hwang, Pil Gyu; Bing, Zhanyong

    2012-01-01

    The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was composed of sheets of medium-to-large cells with foamy and reticulated cytoplasm and small-to-medium sized nuclei with variably prominent nucleoli. Oil red O stain showed abundant intracellular lipid. Periodic Acid-Schiff stain confirmed the presence of abundant glycogen deposition. Immunohistochemically the tumor cells were positive for Hep Par1, negative for epithelial membrane antigen, steroidogenic factor-1, HMB45, melan A, CK7 and CK20. Electron microscopy study was performed, which was first done in a clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without elevation of liver function tests. Ultrastructural evaluation of the clear cells showed scarce cellular organelles, cytoplasmic lipid vacuoles and swollen mitochondria. PMID:22826786

  2. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma

    PubMed Central

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-01-01

    Abstract Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent. The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC. Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies. A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65–0.68), 0.88 (95% CI: 0.87–0.90), 7.13 (95% CI: 5.73–8.87), and 0.33 (95% CI: 0.29–0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies. PMID:27124038

  3. A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin

    PubMed Central

    Huang, Chen-Yang; Lu, Chang-Hsien; Yang, Chan-Keng; Hsu, Hung-Chih; Kuo, Yung-Chia; Huang, Wen-Kuan; Chen, Jen-Shi; Lin, Yung-Chang; Chia-Yen, Hung; Shen, Wen-Chi; Chang, Pei-Hung; Yeh, Kun-Yun; Hung, Yu-Shin; Chou, Wen-Chi

    2015-01-01

    Abstract Carcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients. We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated. The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ≤3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively. In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments. PMID:26632736

  4. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma.

    PubMed

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-04-01

    Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent.The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC.Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies.A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65-0.68), 0.88 (95% CI: 0.87-0.90), 7.13 (95% CI: 5.73-8.87), and 0.33 (95% CI: 0.29-0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies.

  5. Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

    SciTech Connect

    Kelly, Patrick; Das, Prajnan; Varadhachary, Gauri R.; Fontanilla, Hiral P.; Krishnan, Sunil; Delclos, Marc E.; Jhingran, Anuja; Eifel, Patricia J.; Crane, Christopher H.

    2012-04-01

    Objectives: Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis. Patients and Methods: Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed. Results: The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities. Conclusions: The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.

  6. Incidence and Outcomes of Patients With Oral Cavity Squamous Cell Carcinoma and Fourth Primary Tumors

    PubMed Central

    Adel, Mohamad; Liao, Chun-Ta; Lee, Li-Yu; Hsueh, Chuen; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Huang, Shiang-Fu; Kang, Chung-Jan; Fang, Ku-Hao; Wang, Yu-Chien; Chang, Kai-Ping; Fang, Tuan-Jen; Yang, Lan Yan; Yen, Tzu-Chen

    2016-01-01

    Abstract The aim of this study was to explore the incidence and outcomes of patients with oral cavity squamous cell carcinoma (OSCC) and fourth primary tumors (PTs) in a betel-chewing endemic area. We retrospectively examined the records of 1836 OSCC patients who underwent radical tumor resection between 1996 and 2014. The outcome measures included the incidence and number of multiple PTs, the main risk factors, and their associations with overall survival (OS). Of the 1836 patients, 1400 (76.3%) had a single PT, 344 (18.7%) a second PT, 67 (3.6%) a third PT, and 25 (1.4%) a fourth PT. Univariate analyses (log-rank test) identified the following factors as significantly associated with a fourth PT: simultaneous first and second PTs, betel quid chewing, buccal subsite, and pT3–4 status. After allowance for the potential confounding effect of other risk factors, all of these factors retained their independent prognostic significance in stepwise multivariate analyses, the only exception being betel chewing. The incidences of second, third, and fourth PTs at 5 and 10 years were 20.2%/34.6%, 4.0%/8.6%, and 1.0%/2.3%, respectively. The 5 and 10-year OS rates (calculated from the diagnosis of each PTs) for patients with a single, second, third, and fourth PTs were 68%/61%, 43%/37%, 45%/39%%, and 30%/30%, respectively (P < 0.0001). Among patients with a fourth PT, those who underwent radical surgery showed a significantly higher 3-year OS than those who did not (57% vs 13%; P = 0.0442). Fourth PTs are rarely observed in OSCC patients in a betel quid-chewing endemic area. Long-term survival rates of patients treated with radical surgery seems acceptable, being 4-fold higher than their counterparts. PMID:27015170

  7. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma.

    PubMed

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-04-01

    Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent.The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC.Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies.A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65-0.68), 0.88 (95% CI: 0.87-0.90), 7.13 (95% CI: 5.73-8.87), and 0.33 (95% CI: 0.29-0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies. PMID:27124038

  8. Intracardiac metastasis from known cervical cancer: a case report and literature review.

    PubMed

    Byun, Seung Won; Park, Sung Taek; Ki, Eun Young; Song, Hyun; Hong, Suk Hee; Park, Jong Sup

    2013-05-23

    Cardiac metastasis from known cervical cancer is rare. Even through a routine check-up, this type of metastasis can present as pulmonary emboli. Suspicion of this diagnosis in an oncology patient with complicating pulmonary emboli but no evidence of deep vein thrombosis is important, especially in cervical cancer patients with extensive pelvic lymph node metastasis and vascular invasion of a primary tumor. Early recognition may aid in improving the prognosis. We present a case of intracardiac metastasis arising from a squamous carcinoma of the cervix in a patient with pulmonary tumor emboli and review other cases from the literature.

  9. Ovarian and cervical cancer.

    PubMed Central

    Williams, C.

    1992-01-01

    Death rates from cervical cancer have already fallen this century and for patients with invasive cervical cancer five year survival rates are greater than for most solid tumours. Better screening for premalignant changes may further reduce the incidence of invasive cancer; indeed, it has been claimed that the reduction in mortality could be as high as 90%, though estimates of screening efficacy have varied greatly. For those with advanced invasive carcinoma neoadjuvant chemotherapy may reduce the risk of relapse and improve survival. Images FIG 2 p1504-a PMID:1611377

  10. Multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects of a population of more than 5,000

    SciTech Connect

    Niibe, Yuzuru . E-mail: joe-n@hkg.odn.ne.jp; Kenjo, Masahiro; Kazumoto, Tomoko; Michimoto, Koichi; Takayama, Makoto; Yamauchi, Chikako; Kataoka, Masaaki; Suzuki, Kazunori; Ii, Noriko; Uno, Takashi; Takanaka, Tsuyoshi; Higuchi, Keiko; Yamazaki, Hideya; Tokumaru, Sunao; Oguchi, Masahiko; Hayakawa, Kazushige

    2006-12-01

    Purpose: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study. Patients and Methods: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanese hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7-2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25-60 Gy). Results: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% (p = 0.018). Three-year overall survival rates of the total dose {>=}51 Gy and that of {<=}50 Gy were 58.0% and 42.8%, respectively (p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity. Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.

  11. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    PubMed Central

    Takatori, Eriko; Shoji, Tadahiro; Takada, Anna; Nagasawa, Takayuki; Omi, Hideo; Kagabu, Masahiro; Honda, Tatsuya; Miura, Fumiharu; Takeuchi, Satoshi; Sugiyama, Toru

    2016-01-01

    Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass.

  12. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    PubMed Central

    Takatori, Eriko; Shoji, Tadahiro; Takada, Anna; Nagasawa, Takayuki; Omi, Hideo; Kagabu, Masahiro; Honda, Tatsuya; Miura, Fumiharu; Takeuchi, Satoshi; Sugiyama, Toru

    2016-01-01

    Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass. PMID:27695343

  13. The diagnostic value of 1.5-T diffusion-weighted MR imaging in detecting 5 to 10 mm metastatic cervical lymph nodes of nasopharyngeal carcinoma

    PubMed Central

    Jin, Guan Qiao; Yang, Jun; Liu, Li Dong; Su, Dan Ke; Wang, Duo Ping; Zhao, Sheng Fa; Liao, Zhi Ling

    2016-01-01

    Abstract The aim of the study was to prospectively assess the diagnostic accuracy of 1.5 T diffusion-weighted imaging (DWI) for 5 to 10 mm metastatic cervical lymph nodes of patients with nasopharyngeal carcinoma (NPC). All patients with histopathologically confirmed NPC underwent DWI with 2 b values of 0 and 800 s/mm2 were enrolled. The shortest axial diameter and mean apparent diffusion coefficient (ADC) value were recorded when lymph nodes with a shortest axial diameter from 5 to 10 mm were measured. The correlation between the pathological diagnoses and mean ADC values in the benign and metastatic lymph nodes were compared using the Z test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of DWI. Three hundred fourteen nodes of 52 patients with NPC consisted of 46.5% (146/314) metastatic lymph nodes and 53.5% (168/314) benign lymph nodes. The mean ADC value (×10–3 mm2/s) of benign lymph nodes was (1.110 ± 0.202), which was significantly higher than that of metastatic nodes (0.878 ± 0.159) (P < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value, accuracy for differentiating metastatic from benign lymph nodes using a cutoff ADC value of 0.924 × 10–3 mm2/s was 83.56%, 82.74%, 80.79%, 85.28%, and 82.80%, respectively. The area under the ROC curve was 0.851 (95% confidence intervals: 0.807–0.889). This study demonstrated that DWI is helpful in detecting 5 to 10 mm metastatic lymph nodes of patients with NPC. PMID:27512841

  14. Anticancer Activity of Certain Herbs and Spices on the Cervical Epithelial Carcinoma (HeLa) Cell Line.

    PubMed

    Berrington, Danielle; Lall, Namrita

    2012-01-01

    Acetone extracts of selected plant species were evaluated for their in vitro cytotoxicity against a noncancerous African green monkey kidney (Vero) cell line and an adenocarcinoma cervical cancer (HeLa) cell line. The plants studied were Origanum vulgare L. (Oregano), Rosmarinus officinalis L. (Upright and ground cove rosemary), Lavandula spica L. (Lavender), Laurus nobilis L. (Bay leaf), Thymus vulgaris L. (Thyme), Lavandula x intermedia L. (Margaret Roberts Lavender), Petroselinum crispum Mill. (Curly leaved parsley), Foeniculum vulgare Mill. (Fennel), and Capsicum annuum L. (Paprika). Antioxidant activity was determined using a quantitative DPPH (1,1-diphenyl-2-picryl hydrazyl) assay. The rosemary species exhibited effective radical scavenging capacity with 50% inhibitory concentration (IC(50)) of 3.48 ± 0.218 μg/mL and 10.84 ± 0.125 μg/mL and vitamin C equivalents of 0.351 g and 1.09 g for McConnell's Blue and Tuscan Blue, respectively. Cytotoxicity was measured using XTT (Sodium 3'-[1-(phenyl amino-carbonyl)-3,4-tetrazolium]-bis-[4-methoxy-6-nitro] benzene sulfonic acid hydrate) colorimetric assay. Only L. nobilis and O. vulgare exhibited pronounced effects on the HeLa cell line. Dose-dependent studies revealed IC(50) of 34.46 ± 0.48 μg/mL and 126.3 ± 1.00 μg/mL on the HeLa cells and on the Vero cells 124.1 μg/mL ± 18.26 and 163.8 μg/mL ± 2.95 for L. nobilis and O. vulgare, respectively. Light (eosin and haematoxylin staining) and confocal microscopy (Hoechst 33342, acridine orange, and propidium iodide staining) were used to evaluate the cytotoxic mechanism of action for L. nobilis and O. vulgare. PMID:22649474

  15. Recurrence patterns and prognostic factors in Chinese patients with squamous cell carcinoma of the vulva treated with primary surgery.

    PubMed

    Cheng, Xi; Zang, Rongyu; Wu, Xiaohua; Li, Ziting; Cai, Shumo; Zhang, Zhiyi

    2009-01-01

    The purpose of this study was to identify the prognostic factors for disease-free survival (DFS) and recurrence patterns in Chinese women with squamous cell carcinoma of the vulva treated with primary surgery. From 1980 through 2002, 100 patients with invasive squamous cell carcinoma of the vulva treated with primary surgery were included in this retrospective study. Survival analyses included the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. The 5- and 10-year DFS rates were 66.5% and 45.2%, respectively. Among all the tumor-related variables age, International Federation of Gynecology and Obstetrics stage, lymphovascular space invasion, and lymph node status were found to be significant predictors of DFS for the univariate analysis. Multivariate analysis proved that age (risk ratio, 6.572; 95% confidence interval, 1.759-24.546) and lymph nodes metastasis (risk ratio, 4.178; 95% confidence interval, 1.358-12.855) were the most significant prognostic factors of DFS (P < 0.05). The overall recurrence rate was 34.0% (34/100). Among the patients with recurrences, the locations of the recurrent disease were as follows: local recurrence in 20 (58.8%), groin recurrence in 2 (5.9%), local and groin in 1 (2.9%), distant metastases in 5 (14.7%), and local recurrence and distant metastases in 5 (14.7%); data were missing for 1 (2.9%) patients. Older age and lymph nodes metastases were the independent predictors of poor prognosis for patients with invasive squamous cell carcinoma of the vulva treated with primary surgery. Local recurrence was the main recurrence pattern after primary surgery which would be improved by multidisciplinary treatment.

  16. Prognostic Value of the Sum of Metabolic Tumor Volume of Primary Tumor and Lymph Nodes Using 18F-FDG PET/CT in Patients With Cervical Cancer

    PubMed Central

    Hong, Jin Hwa; Min, Kyung Jin; Lee, Jae Kwan; So, Kyeong A; Jung, Un Suk; Kim, Sungeun; Eo, Jae Seon

    2016-01-01

    Abstract This is an observational study to determine the most relevant parameter of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence in cervical cancer. Fifty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer who underwent pretreatment 18F-FDG PET/CT were enrolled. PET parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of both primary tumor and pelvic and/or para-aortic lymph nodes were analyzed. SUVmax-S was defined as the sum of the SUVmax of primary tumor and the higher SUVmax of either pelvic or para-aortic lymph nodes. MTV-S was defined as the sum of the MTV of primary tumor and pelvic and para-aortic lymph nodes. TLG-S was calculated in the same way as MTV-S. We evaluated the relationship between these PET parameters and recurrence-free survival (RFS). Univariate analysis revealed that higher FIGO stage (hazard ratio [HR] = 5.61, 95% confidence interval [CI]: 1.68–18.68, P = 0.005), lymph node metastasis (HR = 3.42, 95% CI: 1.08–10.84, P = 0.037), MTV of primary tumor >47.81 cm3 (HR = 6.20, 95% CI: 1.35–28.48, P = 0.019), TLG of primary tumor >215.02 (HR = 11.82, 95% CI: 1.52–91.96, P = 0.018), MTV-S > 59.01 cm3 (HR = 8.24, 95% CI: 1.80–37.77, P = 0.007), and TLG-S > 224.15 (HR =  13.09, 95% CI: 1.68–101.89, P = 0.014) were associated with RFS. In multivariate analysis, FIGO stage (HR = 4.87, 95% CI: 1.38–17.18, P = 0.014) and MTV-S > 59.01 cm3 (HR = 7.37, 95% CI: 1.54–35.16, P = 0.012) were determined to be independent predictive factors for RFS. Our preliminary results reveal that MTV-S is an independent prognostic factor for RFS in patients with cervical cancer treated by definitive chemoradiotherapy. PMID:26945420

  17. XH1--a new cervical carcinoma cell line and xenograft model of tumour invasion, 'metastasis' and regression.

    PubMed Central

    Han, X.; Lyle, R.; Eustace, D. L.; Jewers, R. J.; Parrington, J. M.; Das, A.; Chana, T.; Dagg, B.; Money, S.; Bates, T. D.

    1991-01-01

    A new cell line, XH1, has been derived from an invasive focally keratinising adenosquamous carcinoma of the cervix in a 32 year old patient. It has been maintained in long term monolayer culture for 26 months, and passaged over 100 times (much greater than 300 population doublings). It is aneuploid with a mean chromosome number of 78. Examination using two minisatellite hypervariable DNA probes has shown it to be different from other cell lines maintained in this laboratory and from HeLa. Two sublines, XH1a and XH1b, show marked differences in monolayer culture, growth in soft agar, and xenograft formation. XH1 and XH1a cells readily form subcutaneous xenografts, and lung colonies can be established by their intravenous injection. Subcutaneous injection of XH1b cells results in rapid cell growth for a few days after which the tumour undergoes degeneration and then regresses completely. The XH1 karyotype has many rearranged chromosomes. Parental XH1 cells and both sublines show integration of HPV16 into the genome. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 9 Figure 7 Figure 8 Figure 10 Figure 13 Figure 14 Figure 11 Figure 12 Figure 15 Figure 16 Figure 17 Figure 18 PMID:1911212

  18. Sensitivity of cervical carcinoma cells to vesicular stomatitis virus-induced oncolysis: potential role of human papilloma virus infection.

    PubMed

    Le Boeuf, Fabrice; Niknejad, Nima; Wang, Jiahu; Auer, Rebecca; Weberpals, Johanne I; Bell, John C; Dimitroulakos, Jim

    2012-08-01

    High-risk carcinogenic subtypes of human papilloma virus (HPV) are associated with the development of squamous cell carcinomas of the cervix (CC) and a subset of head and neck (HNSCC). Recurrent metastatic diseases of these sites display a dismal prognosis. Therefore, there is an urgent need to uncover innovative therapeutic strategies in this clinical setting. Oncolytic viruses, including vesicular stomatitis virus (VSV), were identified due to their ability to specifically target tumor cells that generally display defects in interferon (IFN) signaling. HPV expressed proteins can inhibit IFN signaling; therefore, HPV-infected cells may be particularly sensitive to VSV oncolysis. In this study, we evaluated the sensitivity of four CC (HPV+) and four HNSCC (HPV-) derived cell lines to VSV oncolysis. Interestingly, the CC cell lines were consistently more sensitive to VSV cytotoxicity than the HNSCC cell lines tested. Exogenous IFN addition or infection with two attenuated VSV variants that are more susceptible to IFN inhibition failed to attenuate VSV oncolysis in hypersensitive CC cell lines. Furthermore, the expression of HPV-E6, that inhibits IFN receptor signaling, in the VSV-resistant HNSCC cell line SCC25 attenuated VSV-induced IFN response and significantly enhanced VSV cytotoxicity. Finally, differential VSV infection and replication was confirmed in xenograft murine tumor models and explant tumor tissues from two patients with CC. Taken together, these results demonstrate that HPV-infected cells are susceptible to oncolytic virus therapy and that this approach may represent a novel therapeutic approach in HPV positive CC and HNSCC patients.

  19. Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany

    PubMed Central

    Sroczynski, Gaby; Schnell-Inderst, Petra; Mühlberger, Nikolai; Lang, Katharina; Aidelsburger, Pamela; Wasem, Jürgen; Mittendorf, Thomas; Engel, Jutta; Hillemanns, Peter; Petry, Karl Ulrich; Krämer, Alexander; Siebert, Uwe

    2010-01-01

    Background Persistent infections with high-risk types of human papillomavirus (HPV) are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. Research questions What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained) of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG) of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? Methods A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER). The perspective of the third party payer and 3% annual discount rate were adopted. Extensive

  20. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    PubMed

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  1. A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma

    SciTech Connect

    Devereux, Thomas; Pham, Daniel; Kron, Tomas; Foroudi, Farshad; Supple, Jeremy; Siva, Shankar

    2015-04-01

    This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dose to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30 cm{sup 3} of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30 cm{sup 3} of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.

  2. A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma.

    PubMed

    Devereux, Thomas; Pham, Daniel; Kron, Tomas; Foroudi, Farshad; Supple, Jeremy; Siva, Shankar

    2015-01-01

    This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dose to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30cm(3) of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30cm(3) of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.

  3. Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

    PubMed Central

    2014-01-01

    Background To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. Methods One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Results Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). Conclusions PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor

  4. Primary squamous cell carcinoma with mucormycosis in a diabetic foot ulcer.

    PubMed

    Mandal, Palash Kumar; Bhattacharyya, Nirmal Kumar; Mookerjee, Sekhar Kumar; Chaudhuri, Bhaskarnarayan

    2013-02-01

    The diabetic foot ulcer is one of the major complications of diabetes mellitus leading to prolonged hospital stay. Non-healing foot ulcers in diabetes may be due to peripheral neuropathy and/or vasculopathy. Non-healing occurs following a trivial trauma due to loss of local immunity and increased infection by bacteria and fungus. Candida and mucormycosis are common fungal infection in diabetic foot ulcer. Squamous cell carcinoma in any non-healing ulcer is a common occurrence. But squamous cell carcinoma in non-healing diabetic foot ulcer is rarely reported. Here, mucormycosis in a diabetic foot ulcer which turned into squamous cell carcinoma is reported in a 62-year-old male with poor glycaemic control for last 21 years who presented with a non-healing ulcer of 8 months' duration over dorsum of left forefoot. Microbiological examination revealed presence of mucormycosis infection and histopathology of ulcer showed infiltrating well-differentiated squamous cell carcinoma. The clinicians and pathologists should be aware of these combinations because only eradication of mucormycosis may not cure the ulcer, rather presence of squamous cell carcinoma may be ignored that may be an immediate threat to the patient's life.

  5. Incidence of cervical lymph node metastasis and its association with outcomes in patients with adenoid cystic carcinoma. An international collaborative study

    PubMed Central

    Amit, Moran; Binenbaum, Yoav; Sharma, Kanika; Ramer, Naomi; Ramer, Ilana; Agbetoba, Abib; Glick, Joelle; Yang, Xinjie; Lei, Delin; Bjørndal, Kristine; Godballe, Christian; Mücke, Thomas; Wolff, Klaus-Dietrich; Fliss, Dan; Eckardt, André M.; Copelli, Chiara; Sesenna, Enrico; Palmer, Frank; Ganly, Ian; Patel, Snehal; Gil, Ziv

    2016-01-01

    Background The patterns of regional metastasis in adenoid cystic carcinoma (ACC) of the head and neck and its association with outcome is not established. Methods We conducted a retrospective multicentered multivariate analysis of 270 patients who underwent neck dissection. Results The incidence rate of neck metastases was 29%. The rate observed in the oral cavity is 37%, and in the major salivary glands is 19% (p = .001). The rate of occult nodal metastases was 17%. Overall 5-year survival rates were 44% in patients undergoing therapeutic neck dissections, and 65% and 73% among those undergoing elective neck dissections, with and without nodal metastases, respectively (p = .017). Multivariate analysis revealed that the primary site, nodal classification, and margin status were independent predictors of survival. Conclusion Our findings support the consideration of elective neck treatment in patients with ACC of the oral cavity. PMID:25060927

  6. Impact of cervical disease and its definitive radiotherapeutic management on survival: Experience in 2013 patients with squamous cell carcinomas of the oropharynx and pharyngolarynx

    SciTech Connect

    Bataini, J.P.; Bernier, J.; Jaulerry, C.; Brunin, F.; Pontvert, D. )

    1990-07-01

    Two thousand thirteen patients with squamous cell carcinoma of oropharynx and pharyngolarynx were reviewed with regard to neck disease presentation and disease-free survival after radical radiotherapy. All patients were staged according to both the AJCC 1976 and the UICC 1978 classifications. Causes of failure, disease-free survival, and complication rates were assessed. Sixty percent had a clinically positive neck. The 3-year disease-free survival rates were 58%, 44%, 38%, and 25% for AJCC N0, N1, N2, and N3 cases, respectively. Corresponding UICC figures were 58%, 46%, 26%, and 29%. Analyzed parameters were nodal stage, size, site and fixity, and location of primary. Complications attributed to neck disease did not exceed 3%. A critical appraisal of the nodal staging systems is derived from these sets of data.

  7. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells.

    PubMed

    Matthew, Elizabeth M; Zhou, Lanlan; Yang, Zhaohai; Dicker, David T; Holder, Sheldon L; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J; Lamparella, Nicholas E; Truica, Cristina I; El-Deiry, Wafik S

    2016-01-26

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing.

  8. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells

    PubMed Central

    Yang, Zhaohai; Dicker, David T.; Holder, Sheldon L.; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J.; Lamparella, Nicholas E.; Truica, Cristina I.; El-Deiry, Wafik S.

    2016-01-01

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing. PMID:26695546

  9. Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

    SciTech Connect

    Wootton, Jeffery H.; Hsu, I-Chow Joe; Diederich, Chris J.

    2011-02-15

    Purpose: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Methods: Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 deg.), bisectored (2x180 deg.), or trisectored (3x120 deg.) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. Results: The CTV in HDR brachytherapy plans extends 20.5{+-}5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4{+-}7.3 mm from the tandem. Simulations indicate that for 60

  10. BILATERAL SUPERFICIAL CERVICAL BLOCKS AS THE PRIMARY ANESTHETIC FOR THE PATIENT UNDERGOING AN EVACUATION OF NECK HEMATOMA AFTER PARATHYROID SURGERY.

    PubMed

    Heller, Benjamin; Levine, Adam

    2015-10-01

    This is the case of an 80-year-old female who presented for evacuation of a neck hematoma on POD#3 after a parathyroidectomy. Her medical history included coronary artery disease with a drug-eluding stent, off aspirin for 2 weeks. She had a significant hematoma from the hyoid bone extending down to below the suprasternal notch. She reported hoarseness. The anesthesiology team provided regional anesthesia with bilateral superficial cervical blocks, supplemented with minimal sedation for patient compliance. The surgical team used no adjuvant local anesthetic. A deep exploration was performed and significant clot was evacuated. The patient went home safely from the PACU. PMID:26860031

  11. Primary adrenal sarcomatoid carcinoma metastatic to the lung: Case report and review of the literature

    PubMed Central

    ZHU, CHUANGZHI; ZHENG, AIPING; MAO, XIANGMING; SHI, BENTAO; LI, XIANXIN

    2016-01-01

    Adrenal sarcomatoid carcinoma is a rare adrenal carcinoma. To the best of our knowledge, only 11 cases have been reported since 1987. Adrenal sarcomatoid carcinoma presents a diagnostic challenge due to its atypical symptoms and histological patterns. At the time of diagnosis, a large percentage of patients are already at the metastatic stage and succumb within a few months. The present study reports a case of a 59-year-old man presenting with asthenia and weight loss with adrenal sarcomatoid carcinoma metastatic to the lung. A computed tomography (CT) scan and ultrasonography of the patient's abdomen suggested a large homogeneous mass in the right adrenal gland, and a CT scan of his chest suggested lung metastasis. Right adrenalectomy was performed. Histological examination revealed that the tumor was composed of sarcomatous and carcinomatous differentiation elements. Immunohistochemical examination revealed tumor cell positivity for vimentin and cytokeratin. At the 6-month follow-up the patient exhibited no disease progression and refused further proposed treatment. The patient was alive at the time of writing the current report. The present case report additionally reviews the literature, for the purpose of raising awareness of these rare lesions and assisting in achieving accurate diagnoses and effective treatment. PMID:27123074