Role of Surgery in locally advanced prostate cancer

A significant proportion of patients present with locally advanced prostate cancer with inherent higher risk of local recurrence and systemic relapse after initial treatment. Recent literature favors combination of radiation therapy and extended hormonal therapy for this subset of patients. The effectiveness of Radical prostatectomy (RP) alone for locally advanced prostate cancer is controversial and is a focus of debate. However, it can decrease the tumor burden and allows the accurate and precise pathological staging with the need for subsequent treatment. Comparison of RP and other treatment modalities is difficult and incorrect because of inherent selection bias. RP as a part of multi-modality treatment (with neo-adjuvant hormonal therapy (HT) and with adjuvant or salvage radiation therapy (RT)/HT) can provide long term overall and cancer specific survival. Surgical treatment (such as transurethral resection (TUR), JJ stenting and percutaneous nephrostomy (PCN) placement etc.) can also provide symptomatic improvement and palliative care to improve quality of life of patients with advanced prostate cancer

Functional and clinical outcome of ileal (Studer) neo-bladder reconstruction: Single centre experience from Pakistan

Objective: To determine the medium and long-term outcome of orthotopic continent urinary diversion with ileal (Studer) neo-bladder following radical cystectomy. Study Design: Case series. Place and Duration of Study: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 1998 to September 2010. Methodology: Thirty eight patients underwent radical cystectomy for invasive bladder tumor with ileal neo-bladder (Studer type) reconstruction. Peri-operative and late complications, functional outcome of neo-bladder, urinary continence, metabolic and upper urinary tract status and overall survival were evaluated in all patients. Results: A total of 29 patients (23 males and 6 females) with mean age of 59 ± 12 years were included for the final analysis. The mean duration of surgery (both radical cystectomy and urinary diversion) was 520 ± 70 minutes. Perioperative complication rate was 24% (n=7) with surgical site infection in 4 patients, sepsis in 1 patient and 2 had ureteroileal leak. At 6 months follow-up, 22 patients were fully continent while 7 patients had minimal stress / nocturnal incontinence. The continence rate was 93% (n=27) at one year follow-up. The mean capacity of neo-bladder at 6 months was 384 ± 66 mLs. The late complication rate was 17% (n=5). Three patients developed anastomotic stricture requiring transurethral incision of neo bladder neck, one formed stone in neo-bladder and one developed incision hernia. All patients had preserved renal functions on follow-up. The survival rate was 80% (n=23) at a median follow-up of 66.4 ± 36 months. Two patients developed local recurrence and four developed distant metastasis. Conclusion: Studer ileal neo-bladder is a safe and effective option for urinary diversion in select patients with good oncological and functional outcomes comparable to contemporary literature, even in a low volume center

Pheochromocytoma associated with von Hippel-lindau disease in a Pakistani family

Objectives: The aim was to study the presentation, disease characteristics, operative outcome, and prognosis in patients with familial Pheochromocytoma associated with von Hippel-Lindau (VHL) disease.Materials and Methods: There were six patients belonging to two generations of a single family who developed features of VHL over a period of 13 years and were treated at our institute. Patients\u27 characteristics, that is, age, gender, presenting complaints and clinical signs, laboratory and biochemical evaluation, and the presence of associated conditions was gathered from medical records. The preoperative and postoperative radiological imaging and histopathological results were also collected.Results: Out of six cases, five were male, and one was female. The mean age at first presentation was 25 years (16-40). All patients presented with uncontrolled hypertension and were found to have Pheochromocytoma on workup. Three patients had unilateral adrenal tumor, and three had bilateral disease. None of the patients had extra-adrenal Pheochromocytoma. All patients were managed with adrenalectomy and had benign pathology. Two patients subsequently had craniotomy for excision of cerebellar hemangioma, and one patient had bilateral partial nephrectomy at the time of adrenalectomy. There was no peri- post-operative mortality and all patients are being followed by the surgeon(s) and endocrinologist.Conclusion: Pheochromocytoma can be a part of familial conditions including VHL. Other associated features should be suspected, investigated, and treated in these patients that can influence patients\u27 clinical course and prognosis. Family members should also be screened to achieve early diagnosis

An unusual combination of extra-adrenal pheochromocytoma and arteriovenous malformation of the ureter in a young adult

We present a case of a 24-year-old gentleman who presented with painless pan haematuria for 2 weeks. During the workup, he was diagnosed to have a retrocaval mass after a CT scan while cystoscopy revealed a polypoidal pulsating lesion in the left ureter. After surgical manipulation of the retrocaval mass, the blood pressure of the patient raised to 260/130 mm Hg. It was completely resected and diagnosed as extra-adrenalpheochromocytoma (paraganglioma) after histopathology. The lesion in the ureter was completely excised and fulgurated and diagnosed as anarteriovenous malformation. To the best of our knowledge, this is the first patient to be presented in the literature with this unusual combination

HIV-1 subtype A gag variability and epitope evolution

Objective: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes.Methods: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined. Results: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 ± 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010. Conclusion: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences

Mediastinal parathyroid adenoma causing primary hyperparathyroidism

An ectopically placed parathyroid adenoma in the anterior mediastinum is a rare cause of persistent or recurrent primary hyperparathyroidism (PHPT) and is recognized as an important cause of failed primary neck exploration. We encountered 3 such cases amongst 70 surgically treated patients with PHPT (4.3%) over a 20-year period. In 2 cases, the offending adenoma could be removed at first exploration whereas in the 3rd case, it was successfully removed with mediastinal exploration after 2 failed neck explorations. In established cases of PHPT with equivocal preoperative localization studies or negative neck explorations, an ectopically placed parathyroid adenoma should be considered and once localized, should be surgically removed for cure

Nephron sparing surgery for renal tumors-Comparison of off-clamp partial nephrectomy with hilar clamping

Background and objective: Open partial nephrectomy (PN) is still considered gold standard procedure for T1 localized renal tumors. Conventional technique involves clamping of the renal artery with or without vein however, renal ischemia produces a certain level of damage to the kidneys. This study aims to investigate potential effect of off-clamp vs. hilar clamping PN on renal function.Methods: This is a retrospective cohort study of patients who underwent unilateral, open partial nephrectomy for renal tumors b/w January 2009 December 2016 at our institution. A total of 90 partial nephrectomies were performed of which 65 cases were eligible for analysis. Non clamping technique was used in 43 while clamp was applied in 22 patients. Variables studied were patients\u27 demographics, clinical variables, the laterality, tumors size and location, R.E.N.A.L nephrometry score, blood loss, tumor histology and surgical margins. Patients\u27 renal function (serum creatinine and eGFR) were determined pre-operatively, at 3 and 12 months follow up. Data was analyzed on SPSS v. 22.Results: Both the groups were comparable with regards to pre-operative renal function. Mean radiological size of tumor was 4.71±1.31 and 3.81±1.0 (0.003) in two groups respectively. Mean R.E.N.A.L nephrometry score was 6.1±1.5 in off-clamp group compared to 7.05 ± 1.7 in clamp group (p=0.04). No statistically significant difference was found in operative duration, blood loss, positive surgical margins and intra/ peri-operative complications. At three months and one year, renal function was better preserved in non-clamp group compared to clamp group (p=0.001 and 0.007 respectively).Conclusion: Off clamp open partial nephrectomy is safe and feasible option leading to less decline in renal function

Early surgical results with intent to treat by radical retropubic prostatectomy for clinically localized prostate cancer

Aims: To evaluate the early cancer control rates, morbidity and mortality in men undergoing radical retropubic prostatectomy (RRP) for clinicallylocalized adenocarcinoma prostate.Methods: Patient\u27s characteristics, operative data, progressive-free survival rates, morbidity and mortality were analyzed for 23 men with clinical T1-2 prostate cancer who underwent surgery with an intent to treat by RRP between December 1997 to July 2001.Results: Patient\u27s mean age was 63 +/- 6.2 years (range 51 to 76 years) with American Society of Anesthesiology (ASA) status I in 4%, II in 65% and III in 31%. Two third of the patients had lower urinary tract obstructive symptoms, followed by hematuria (9%) and back pain (4%). Clinical stages were T1b in 4%, T1c in 9%, T2a in 17%, T2b in 22% and T2c in 48% of the patients. Mean pre-operative serum prostate specific antigen (PSA) was 25 +/- 29 ng/ml (1.1 to 99.3). Bilateral pelvic lymphnode disection(PLND) and RRP was performed in 20 cases (nerve-sparing RRP 5 cases). In 3 cases with gross lymph node metastasis at frozen section, only bilateral orchidectomy was done. The mean operative time was 270 +/- 65 minutes and mean blood loss was 1097 +/- 654 mls. Packed cell transfusions were nil in 26%, 1-2 units in 44%, 3-4 units in 26% and 5 units in 4% of the patients who underwent RRP. The mean length of hospital stay was 10.2 +/- 1 days. Out of 20 patients who underwent RRP, 65% of tumors were confined to the specimen, 20% had seminal vesicle invasion and 15% had nodal metastasis. There was no peri-operative mortality while 2 patients developed epididymo-orchitis and 1 had myocardial ischemia (without infarction). Overall 87% of the patients were fully continent and 13% had mild to moderate stress urinary incontinence. The mean time of return of continence was 11.5 +/- 11.6 weeks. Two of the 3 patients (66%) with follow up information and having undergone nerve-sparing RRP are potent. At a mean follow up of 19.4 +/- 13 months (range 3-45 months), 20 of 23 total patients (87%) and 17 of 20 RRP patients (85%) remained free of disease recurrence with PSA \u3c or = 0.4 ng/ml. Conclusion: Our early results confirm the excellent potential for cancer control and low morbidity of radical prostatectomy for men with localizedprostate cancer. These results are in conformity with the vast Western experience. Long-term results will be provided

Role of estrogens in the secondary hormonal manipulation of hormone refractory prostate cancer

Objective: To evaluate the role of Estrogens (Honvan) in the secondary hormonal manipulation of patients with hormone refractory prostate cancer (HRCP). Methods: Twelve patients diagnosed as hormone refractory prostate cancer received intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily as second line hormonal treatment. During the treatment they were given deep venous thrombosis prophylaxis. Their stage at initial presentation, primary treatment, mode of androgen ablation, prostate specific antigen (PSA) level, duration of remission prior of HRPC status, PSA doubling time before and after estrogen treatment were recorded. The morbidity and mortality of the treatment was also recorded. A drop in PSA of \u3e 50% was classified as major responder. The drop of \u3c 50% was defined as minor responders. Treatment failure was defined as a rise in PSA \u3e the level prior to the start of treatment. Results: The mean age at diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of initial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had metastatic prostate cancer. Six patients each opted for surgical or medical castration (LHRH analogs) as the mode of androgen ablation. The mean initial PSA at diagnosis was 340 + 728.1 ng/ml (range 4.1-2375, Median 94). After development of HRPC, six patients (50%) had major response, four (33%) had minor response to estrogen administration. Two patients (17%) did not respond to estrogens. The mean PSA before receiving Fosfestrol was 60.5 + 82 ng/ml (range 0.013-246). The PSA (nadir) after treatment was 24.3 + 33.2 ng/ml (range 0.9-81.3). One patient developed gynaecomastia and one had congestive cardiac failure. Two patients died of non cancer related deaths and one patient died of cancer related death. Conclusion: Synthetic estrogens are well tolerated, in-expensive agents and could be considered for palliative use against hormone resistant prostate cancer (JPMA 54:445;2004)

Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes

Alterations in genomic CpG methylation patterns have been found to be associated with cell transformation and neoplasia. Although it is recognized that methylation of CpG residues negatively regulates gene expression, how the various MBPs (methyl-binding proteins) contribute to this process remains elusive. To determine whether the two well characterized proteins MeCP2 (methyl-CpG-binding protein 2) and MBD1 (methyl-CpG-binding domain 1) have distinct or redundant functions, we employed RNAi (RNA interference) to silence their expression in the prostate cancer-derived PC3cell line, and subsequently compared cell growth, invasion and migration properties of these cell lines in addition to their respective mRNA-expressionprofiles. Cells devoid of MeCP2 proliferated more poorly compared with MBD1-deficient cells and the parental PC3 cells. Enhanced apoptosis was observed in MeCP2-deficient cells, whereas apoptosis in parental and MBD1-deficient cells appeared to be equivalent. Boyden chamber invasion and wound-healing migration assays showed that MBD1-silenced cells were both more invasive and migratory compared with MeCP2-silenced cells. Finally, gene chip microarray analyses showed striking differences in the mRNA-expression profiles obtained from MeCP2- and MBD1-depleted cellsrelative to each other as well as when compared with control cells. The results of the present study suggest that MeCP2 and MBD1 silencing appear to affect cellular processes independently in vivo and that discrete sets of genes involved in cellular proliferation, apoptosis, invasion and migration are targeted by each protein