Hemant B. Tongaonkar

Newer Insights Into Premeiotic Development of Germ Cells in Adult Human Testis Using Oct-4 as a Stem Cell Marker:

The transcription factor octamer-binding transforming factor 4 (Oct-4) is central to the gene regulatory network responsible for self-renewal, pluripotency, and lineage commitment in embryonic stem (ES) cells and induced pluripotent stem cells (PSCs). This study was undertaken to evaluate differential localization and expression of two major transcripts of Oct-4, viz. Oct-4A and Oct-4B, in adult human testis. A novel population of 5- to 10-μm PSCs with nuclear Oct-4A was identified by ISH and immunolocalization studies. Besides Oct-4, other pluripotent markers like Nanog and TERT were also detected by RT-PCR. Adark spermatogonial stem cells (SSCs) were visualized in pairs and chains undergoing clonal expansion and stained positive for cytoplasmic Oct-4B. Quantitative PCR and Western blotting revealed both the transcripts, with higher expression of Oct-4B. It is proposed that PSCs undergo asymmetric cell division and give rise to Adark SSCs, which proliferate and initiate lineage-specific differentiation. The darkly stained nuclei in Adark SSCs may represent extensive nuclear reprogramming by epigenetic changes when a PSC becomes committed. Oct-4B eventually disappeared in mature germ cells, viz. spermatocytes, spermatids, and sperm. Besides maintaining normal testicular homeostasis, PSCs may also be implicated in germ cell tumors and ES-like colonies that have recently been derived from adult human testicular tissue. (J Histochem Cytochem 58:1093–1106, 2010)

Primitive Neuroectodermal Tumor of the Kidney : A Single Institute Series of 16 Patients

OBJECTIVES Primitive neuroectodermal tumor (PNET) of the kidney is a rare entity, the diagnosis usually being made at histopathology. Few cases reported in literature revealed a variable presentation and an aggressive behavior. The purpose of our study was to review our experience in diagnosis and the management of patients with renal PNET. METHODS The records of 16 patients of renal PNET treated between 1995 and 2003 were reviewed retrospectively and our data compared with the literature. RESULTS There were 10 male and 6 female patients with median age of 27 years. At presentation, 10 patients (63%) had localized disease, 5 (31%) had metastatic disease and 1 (6%) had locally advanced disease. The presence of Homer-Wright type rosettes on hematoxylin and eosin staining and CD99 (cluster differentiation) products positivity on immunohistochemistry supported the diagnosis. Radical nephrectomy was performed in operable cases and all patients received chemotherapy. Nine patients received adjuvant radiotherapy to the renal bed. Median follow-up was 31 months (range 4 to 92). Overall median survival was 40 months with 3- and 5-year survival of 60% and 42%, respectively. CONCLUSIONS The diagnosis of renal PNET must be considered in young patients presenting with renal mass. Standard therapy consists of combination of surgical resection, postoperative irradiation and chemotherapy. Chemotherapy regimen used is either RCT II (round cell tumor) protocol or EFT 2001 (Ewings family of tumors) protocol. However, further studies are required to validate the appropriate chemotherapy protocol.

Management of renal cell carcinoma with solitary metastasis

BackgroundDistant metastasis are common in Renal cell carcinoma (RCC) nearly one forth of the patients have metastasis at presentation while another 50% develop metastasis during the follow-up. A small percentage of these are solitary metastasis. We describe survival after surgical excision or radiotherapy of solitary metastatic lesion from renal cell carcinomaPatients and methodsBetween 1988–2001, 43 patients with solitary metastasis to different sites from renal cell carcinoma underwent either surgical excision or radiotherapy were analyzed. The solitary nature of the lesions was confirmed by investigations. All patients have had radical nephrectomy for the primary lesion. Survival analysis was carried out by Kaplan Meier Method.ResultsAll solitary metastatic lesions were treated with intent of cure either by excision or radiotherapy. Of these, 13 patients had solitary metastasis at the time of presentation in whom 3-year overall median survival was 26 months. The survival of those who developed solitary metastases during follow-up after nephrectomy for primary was 45 months. The patients with long interval between diagnosis and development of metastasis, early stage and low grade of the primary tumor had better prognosis.ConclusionComplete resection of either synchronous or metachronous solitary metastases from renal cell carcinoma is justified and can contribute to a long-term survival in this select group of patients.

Adenocarcinoma of bladder

Forty-eight patients with adenocarcinoma (21 urachal and 27 non-urachal) of the bladder were treated at the Tata Memorial Hospital between 1976 and 1992. The study group consisted of 32 men and 16 women. The urachal tumours were more common in younger patients (mean age: 49 years) than were non-urachal tumours (mean age: 58 years). The overall 5-year survival in this series was 37%. Stage and grade were powerful predictors of outcome. Patients with non-urachal tumours showed an overall survival rate of 29.9% compared with 45.7% in patients with urachal tumours (P= 0.14). Radical cystectomy was the most common treatment modality in patients with non-urachal tumours and yielded an overall 5-year survival of 35%. Patients with urachal tumours were treated with either partial cystectomy or radical cystectomy. The 5-year survival following partial cystectomy was 56.3% compared with 25.9% following a radical cystectomy and the difference between the two was not statistically significant (P = 0.76).

Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India.

Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.

Accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms: Experience at a tertiary oncology center

BackgroundEpithelial ovarian neoplasms are an important cause of morbidity and mortality in women. The surgical management of ovarian neoplasms depends on their correct categorization as benign, borderline or malignant. This study was undertaken to evaluate the accuracy of intra-operative frozen section in the diagnosis of various categories of ovarian neoplasms.MethodsIntraoperative frozen section diagnosis was retrospectively evaluated in 217 patients with suspected ovarian neoplasms who underwent surgery as primary line of therapy at our institution. This was compared with the final histopathologic diagnosis on paraffin sections.ResultsIn 7 patients (3.2%) no opinion on frozen section was possible. In the remaining 210 patients frozen section report had a sensitivity of 100%, 93.5% and 45.5% for benign, malignant and borderline tumors. The corresponding specificities were 93.2%, 98.3% and 98.5% respectively. The overall accuracy of frozen section diagnosis was 91.2%. The majority of cases of disagreement were in the mucinous and borderline tumors.ConclusionIntraoperative frozen section has high accuracy in the diagnosis of suspected ovarian neoplasms. It is a valuable tool to guide the surgical management of these patients and should be routinely used in all major oncology centers.

Role of paclitaxel and platinum-based adjuvant chemotherapy in high-risk penile cancer

Aim: To study the efficacy and safety of paclitaxel and platinum doublet chemotherapy in penile cancer patients with high-risk features of local failure. Materials and Methods: Retrospective analysis was done of patients with 19 carcinoma of the penis who were offered adjuvant chemotherapy with paclitaxel and platinum combination. The data regarding the surgical details, high-risk features for which chemotherapy was offered, chemotherapy toxicity details (in accordance with CTCAE vs 3), failure pattern, and survival data were noted. SPSS version 16 was used for statistical analysis. Descriptive and Kaplan–Meier survival analysis was performed. Results: Median age of patients was 48 years. Fifteen patients received paclitaxel in combination with cisplatin and four received paclitaxel with carboplatin in view of their low serum creatinine clearance. The treatment was completed by 12 patients (63.2%). Of 79 planned cycles, 50 were taken. The treatment was well tolerated with grade 3-4 gastrointestinal toxicity was seen in 1 patient, grade 3 neurological toxicity in one and grade 5 neutropenia in one patient. Treatment related death occured in one patient. The median follow-up was 15.33 months and 6 loco-regional relapsed had taken place. The estimated median DFS was 16.2 months and the estimated median OS was not reached. The estimated DFS for treatment completed patients was 23.13 months as against 2.16 months for patients not completing treatment. Conclusion: The platinum and taxane doublet chemotherapy was found to be safe and effective.

RADICAL CYSTOPROSTATECTOMY: AN EXTRAPERITONEAL RETROGRADE APPROACH

PURPOSE We describe a new technical approach for the surgical management of bladder cancer. MATERIALS AND METHODS Patients with invasive bladder cancer underwent radical cystoprostatectomy using a technically different approach than the conventional method. The important features of this modification include a small infraumbilical incision, completely extraperitoneal dissection to maintain the bowel loops away from the operating field, urethral dissection performed earlier in the operation rather than at the end to preserve the striated urethral sphincter with the neurovascular bundles, completely retrograde dissection of the rectovesical plane for increased safety and reperitonealization done at completion to isolate the urinary anastomoses from the bowel anastomosis. RESULTS More than 50 consecutive patients with early bladder cancer underwent this operation during a 2-year period. The technique was safe and satisfactory. CONCLUSIONS Radical retrograde extraperitoneal cystoprostatectomy is based on a finer knowledge of anatomy. It requires accurate dissection, making it inherently superior to the conventional method.

Region-wise distribution of high-risk human papillomavirus types in squamous cell carcinomas of the cervix in India.

Hypothesis: Assessment of the prevalence and type distribution of human papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines in the country and to find out additional types that might be needed to be incorporated in second-generation vaccines. Methods: High-risk (HR) HPVs were genotyped from 667 histopathologically confirmed cases of SCC from 6 different centers representing 4 regions across India: Advanced Centre for Treatment, Research and Education in Cancer, Mumbai; All India Institute of Medical Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain reaction and reverse dot blot assay. Results: Overall viral prevalence across India was not different; 92.1% of 667 cases harbored HPV; 8% were negative. Infection with single HR type was seen in 86.8%: predominant types being HPV-16 followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26, and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other types comprised 12.4%. Conclusions: Prophylactic HPV-16/18-L1 vaccines would provide greater than 75% protection against SCC in India. Ranking and frequencies of non-16/18 types were different from earlier reports. Hence, considering the possibility of promotion of persistence of nonvaccine types in the vaccinees due to original antigenic sin and the lack of organized screening programs in India, a broad-based vaccine approach would be appropriate.

Clinical outcome of 36 male patients with primary urethral carcinoma: A single center experience

Aim:  Retrospective analysis of male urethral carcinoma to assess the best therapeutic approach to the management of this tumor.