Ganesh Bakshi

Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer

BackgroundInfertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro.MethodsThe study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs.ResultsHematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule.ConclusionsThe present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular tissue in young pre-pubertal boys for restoring spermatogenesis in adulthood is still in experimental stages.

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.

Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma.

Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

Clinical impact of prostate specific antigen (PSA) inter-assay variability on management of prostate cancer

PURPOSE To evaluate the inter-assay variability of six commercially available prostate specific antigen (PSA) assays, its clinical impact in prostate cancer (PCa) and comparison of automated versus manual assays. PATIENTS AND METHODS Sera from 495 patients (425 with PCa and 70 men with Benign Prostatic Hyperplasia (BPH), were measured with six different assays [three automated assays (a-PSA) and three manual ELISA based assay (m-PSA)]. Variability, agreement and bias were measured and compared among assays using Bland Altman plots and Passing and Bablok regression analysis. The possible impact of inter-assay variability on important clinical scenarios was also studied. RESULTS All the assays were well correlated (r: 0.88-0.98); however there was significant disagreement and bias between the systems, which were more pronounced among the a-PSA assays. The Bland Altman plot showed that the variability was high between the m-PSA assays and the standard Abbott system with mean difference of 3.8-5.8ng/ml. In contrast, the a-PSA had better agreement with mean difference of 0.8-2.3ng/ml. Beckman Coulter showed the best agreement to the institutional reference (slope-1.097; 95% CI: 1.06-1.14; p<0.05, and intercept-0.20; 95% CI-0.38-0.58; p<0.05, Passing Bablok). It led to significant variability in PCa risk stratification and failure to detect biochemical failure in more than 50% cases. CONCLUSIONS The discrepancies between the assays lead to significant clinical misinterpretation with risk group migration and detection of biochemical failure post radiotherapy. There are significant discordances between automated and ELISA based assays.

Sunitinib in metastatic renal cell carcimoma: a single-center experience.

INTRODUCTION Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine-kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS Fifty-nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose-modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression-free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand-foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow-up is essential for optimum therapy.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study.

PURPOSE The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. METHODS AND MATERIALS Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]10 = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). RESULTS Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. CONCLUSIONS Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.

Bilateral testicular metastasis from prostatic adenocarcinoma mimicking an intertubular pattern of seminoma and expressing Rhamm

Adenocarcinoma of prostate metastasizing to testis is a rare occurrence and is incidentally detected in orchiectomy specimens. The pattern of metastasis may mimic a primary neoplasm of testis like a seminoma or lymphoma and pose a diagnostic difficulty for the pathologist. A rare case of bilateral testicular metastasis of prostatic adenocarcinoma is presented wherein the metastatic cells expressed CD168, a receptor for hyaluronan mediated motility (Rhamm), implicated in the development of androgen independence in prostate cancer.

Pelvic periprostatic symplastic leiomyoma: An unusual case necessitating a radical surgery

Most pelvic smooth muscle tumors are believed to be malignant, leiomyomas are extremely rare; more so in male patients. Very few cases of symplastic leiomyomas have been described in males. We report an extremely unusual case of a soft tissue mass of periprostatic and periseminal vesicle region in a young adult, which necessitated a radical surgery. Histologically, tumor comprised of smooth muscle bundles with numerous bizarre tumor cells which were immunoreactive with smooth muscle actin (SMA), desmin and h-caldesmon. The diagnostic and treatment dilemmas of these unusual tumors are discussed.

Genitourinary cancers: Summary of Indian data

Tumors of the genitourinary system are one of the most common tumors encountered in clinical practice. The associated morbidity and mortality and the significant proportion of affected middle-age individuals have a major bearing on the death-adjusted life years compared to other malignancies. Genitourinary system tumors encompass a very broad spectrum with regard to age, location, histology, and clinical outcomes. Advances in diagnostic imaging, surgical techniques, radiotherapy equipment, and generation of newer chemotherapeutic and targeted agents over the past few years have helped improving treatment outcome. Several focused groups within India have been working on a range of topics related to genitourinary system tumors, and a significant body of work from India in the recent years is being increasingly recognized throughout the world. The present article summarizes the key published work related to the epidemiology of genitourinary system tumors in the Indian setting. A PubMed search was made for locating and selecting articles relevant to the topic.

Current evidence and the evolving role of sunitinib in the management of renal cell carcinoma.

The development of targeted agents has expanded the anticancer arsenal available to oncologists and revolutionized the field of cancer treatment. In patients with advanced renal cell carcinoma (RCC), small molecule targeted therapies have improved clinical outcomes compared with cytokine-based treatments. Sunitinib malate is one such drug that has demonstrated clinical efficacy in patients with metastatic renal cell carcinoma (mRCC). This oral, multi-targeted tyrosine kinase inhibitor is approved for use in multiple countries for the treatment of advanced RCC and gastrointestinal stromal tumor patients who have progressed on imatinib therapy. In patients with advanced RCC, sunitinib significantly improves clinical outcomes with a favorable safety profile compared with conventional treatment with interferon-a. The clinically proven treatment and safety outcomes have led investigators to evaluate the merits of sunitinib therapy in the adjuvant and neoadjuvant setting in patients with mRCC. In the neoadjuvant setting, preliminary data suggest that sunitinib can effectively reduce the primary tumor and facilitate surgical resection in patients with locally advanced and mRCC. Post-operative complications were observed in some patients, but the overall safety profile and efficacy suggests that mRCC patients with surgically inoperable tumors may benefit from neoadjuvant sunitinib therapy. Ongoing clinical trials should provide insight into the value of sunitinib as adjuvant therapy.