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Shomik Sengupta

Publications and source records attributed to Shomik Sengupta.

32 records · Page 2Linked to original sources
PubMed2005

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness.

BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS: The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

Adenocarcinoma, Clear Cell↗
PubMed2005

Surgery for metastatic renal cell cancer.

Renal cell carcinoma (RCC) often presents in its metastatic form, or progresses after curative treatment. While the management of metastatic RCC has historically been mainly surgical, contemporary approaches often incorporate systemic immunotherapy. This review examines the current indications and scope of surgical treatment of patients with metastatic RCC. Surgery is sometimes indicated for symptom palliation at either the primary or secondary sites. However, other less invasive therapies may be equally effective, and should be considered carefully. Cytoreductive surgery prior to immunotherapy appears to confer a survival advantage, but only selected patients are suitable for this treatment regimen. Primary immunotherapy followed by surgical removal of the tumour in partial responders is an alternative treatment strategy, which has not yet been evaluated as in randomized trials. As immunotherapy develops further, the precise timing and role of surgery in multimodality treatment will need to be carefully evaluated. Occasionally, the complete surgical excision of metastases, and the primary tumour, if present, is feasible and this may prolong survival. Empirically, it would seem that such patients should also be treated with adjuvant immunotherapy, as eventual relapse is frequent. Surgery with the aim of inducing spontaneous tumour regression is not justifiable, given the rarity of this phenomenon.

Carcinoma, Renal Cell↗
PubMed2005

The influence of specific luminal factors on the colonic epithelium: high-dose butyrate and physical changes suppress early carcinogenic events in rats.

INTRODUCTION: Although luminal delivery of butyrate is one putative mechanism by which biology of the colonic epithelium might be influenced by changes in luminal contents, there is a paucity of supportive cause-effect evidence. This study aimed to directly establish whether distal colonic butyrate delivery is able to alter the response of the distal colonic epithelium to a carcinogen. METHODS: Groups of male Sprague-Dawley rats with chronically intubated colons received infusions of 80 mM butyrate or 0.9 percent saline into distal colon two or five times daily. Three weeks after exposure to azoxymethane (15 mg/kg subcutaneously), the density of aberrant crypts was quantified in distal colon. RESULTS: Infusions of 0.5 ml twice daily, whether containing saline or butyrate, decreased the number of aberrant crypt foci by 45 percent compared with rats receiving no infusions (P = 0.004, analysis of variance). Similar results were obtained when infusions were restricted to the post-initiation phase. When infusions were increased to 1 ml five times daily, saline infusions similarly suppressed aberrant crypt formation (38 percent), but butyrate infusions suppressed it to a greater degree (by 64 percent; P = 0.02 compared with saline infusion, t-test). CONCLUSIONS: High levels of butyrate delivery to the distal colonic lumen alter the epithelial response to a carcinogen in otherwise healthy rats. This finding directly supports the notion that the effects of butyrate on cells in vitro do occur in vivo provided a sufficient dose is delivered. The effect of infusion of liquid per se on the epithelial response highlights the potential impact physical changes alone can have on the colonic epithelium.

Animals↗
PubMed2005

Lessons learned in the surgical management of renal cell carcinoma.

Surgical excision, the mainstay of management of renal cell carcinoma (RCC), has evolved significantly over the last 4 decades. Radiological imaging is crucial to the diagnosis and staging of RCC, and technological advances have facilitated more precise preoperative assessment. Additionally, wider use of cross-sectional imaging modalities has led to increasing incidental diagnosis of small, early-stage RCC. Nephron-sparing surgery (NSS), originally developed to treat RCC arising in a solitary functioning kidney, has been demonstrated to be a safe and effective alternative to radical nephrectomy. NSS is now also applicable to tumors of suitable size and anatomy in patients with a normal contralateral kidney, thus facilitating preservation of renal function and management of metachronous contralateral pathology. Laparoscopic and percutaneous approaches have developed over the last decade, thus providing minimally invasive modalities, with shortened convalescence and improved cosmesis. Advanced RCC, involving venous extension or nodal spread, is increasingly amenable to surgical management, although appropriate patient selection is crucial. Furthermore, surgical excision of the primary lesion appears to be an integral part of systemic therapy for metastatic RCC.

Carcinoma, Renal Cell↗
PubMed2005

B7-H1 glycoprotein blockade: a novel strategy to enhance immunotherapy in patients with renal cell carcinoma.

Cancer cell expression of the B7-H1 glycoprotein has been implicated as a potent inhibitor of T cell-mediated antitumoral immunity. We recently reported that B7-H1 is aberrantly expressed in renal cell carcinoma (RCC) and suggested that blockade of B7-H1, as demonstrated in several murine cancer models, represents a promising therapeutic target in RCC. Herein, we update our results with tumor-associated B7-H1 and discuss future clinical applications. Between 2000 and 2002, 196 patients underwent nephrectomy for clear-cell RCC and had fresh-frozen tissue available for review. Immunohistochemical analysis was performed on tumor cryosections, and outcome was obtained from the Mayo Clinic Nephrectomy Registry (Rochester, MN). At last follow-up 38 of the 196 patients died of RCC. The median duration of follow-up for patients still alive was 2.7 years. Among the 196 RCC specimens, 130 (66.3%) demonstrated aberrant tumor-associated B7-H1 expression. Patients with tumor-associated B7-H1 expression were significantly more likely to die of RCC compared with patients whose specimens did not have aberrant tumor-associated B7-H1 expression (risk ratio, 3.34; 95% confidence interval [CI], 1.30 - 8.55; P = 0.012). This risk persisted in multivariate analysis even after adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score (risk ratio, 3.52; 95% CI, 1.35-9.15; P = 0.010). Tumor-associated B7-H1 expression is significantly associated with poor prognosis among patients with clear-cell RCC. Manipulation of B7-H1 with therapeutic intent remains a realistic and viable therapeutic option.

Antigens, CD↗
PubMed2005

Preoperative prostate specific antigen doubling time and velocity are strong and independent predictors of outcomes following radical prostatectomy.

PURPOSE: Prostate specific antigen (PSA) is a useful marker for predicting outcomes following treatment for prostate cancer but, given the evolving nature of prostate cancer, there is an ongoing need to refine its use. We assessed preoperative PSA doubling time (PSADT) and PSA velocity (PSAV) as predictors of outcome following radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: We identified 2,290 men who were treated with RRP for prostate cancer between 1990 and 1999 with multiple preoperative PSA measurements available. PSADT was calculated by log linear regression and PSAV was calculated by linear regression. These parameters were used in preoperative and postoperative multivariate models for the end points of biochemical and clinical progression, and cancer death. RESULTS: At a median followup of 7.1 years (range 0.1 to 14.5) biochemical progression, clinical progression and death from prostate cancer were observed in 583, 156 and 42 patients, respectively. The HR for death from prostate cancer was 6.22 (95% CI 3.33 to 11.61) in men with PSADT less than 18 months vs 18 or greater and 6.54 (95% CI 3.51 to 12.19) in men with PSAV greater than 3.4 ng/ml yearly vs 3.4 or less. On multivariate analysis adjusting for preoperative or postoperative variables PSADT and PSAV remained significant predictors of each outcome. When assessed jointly, PSAV was significant as a predictor of biochemical progression, while PSADT was a significant predictor of clinical progression and cancer death. CONCLUSIONS: This study confirms the usefulness of preoperative PSA kinetics for predicting post-RRP outcomes, which may be useful for stratifying patients, so that rational management decisions can be made with respect to observation, intervention and adjuvant treatment. While PSADT maybe biologically more accurate and stronger on multivariate analysis, PSAV is clinically easier to use and a good approximation in the short term.

Adult↗
PubMed2005

The development of prostate cancer despite late onset androgen deficiency.

Androgen withdrawal causes the regression of prostate cancer and is used in therapy, but the role of androgens in the development of prostate cancer is uncertain. We present a case of prostate cancer diagnosed in a man who had been clinically androgen deficient for some years. This case and reviewed literature suggest that while early androgen exposure may be important in the prostatic carcinogenesis, late onset androgen deficiency is not protective. Thus, hypogonadal men considering androgen replacement therapy need to be adequately counseled, screened for prostate cancer and followed closely during treatment.

Age of Onset↗
PubMed2005

Surgical treatment of stage pT3b renal cell carcinoma in solitary kidneys: a case series.

OBJECTIVE: To describe the surgical management of patients with renal cell carcinoma (RCC) in a solitary kidney (managed preferentially by nephron-sparing surgery, NSS, to avoid dialysis) and extending into the renal vein or inferior vena cava (T3b). PATIENTS AND METHODS: We identified 13 patients treated surgically between 1977 and 2002 for stage T3b RCC in a solitary kidney; their charts were reviewed to ascertain details of management, pathology and outcomes. RESULTS: NSS was successful in seven patients (four in situ and three extracorporeally). Five patients had radical nephrectomy (RN), four after failed NSS. The mean (sem) operative duration was longer for NSS, at 5.8 (0.7) h, than RN, at 3.3 (0.6) h. There was one death during surgery before nephrectomy, and eight other complications in six patients. At a median (range) follow-up of 24 (0-204) months, eight patients had died, four from RCC (all having had NSS) at a median interval of 9.5 (7-16) months. Of the five patients alive at a median follow-up of 25 months, four had no identifiable disease, whilst one had systemic recurrence. CONCLUSIONS: NSS combined with venous tumour thrombectomy for treating T3b RCC involving a solitary kidney is feasible, albeit complicated. There was oncological success in a third of the patients. The treatment of these patients needs to be individualized, as alternatives to NSS (RN or observation) have obvious disadvantages.

Adult↗
PubMed2004

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.

Antigens, CD↗
PubMed2002

Development of a chronic colonic intubation model in rats for the study of luminal factors in colonic diseases.

INTRODUCTION: A rat model of long-term colonic intubation has been developed to facilitate the in vivo study of colonic biology. This study aims to characterize this model. METHODS: The effects of intubation and sham surgery on animal behavior and weight gain were measured and compared with unoperated controls. The reproducibility of the model was assessed by comparing complication and failure rates for three operators. The distribution and excretion of infused materials were studied using radiology and gas chromatography of feces, respectively. The effects of the colonic tube and infusions on the mucosa were assessed histologically. RESULTS: There was about 10 percent weight loss postoperatively, more marked in those rats undergoing more extensive surgery. Subsequent weight gain was similar in all groups, and no behavioral effects of surgery were noted. There were no differences in histologic appearances or proliferative indices among the groups. All three operators had similar complication and tube dislodgement rates. Radiologic examination showed even distribution of infusate regardless of fecal consistency. Infusion through the two tubes allowed the cecum and the distal bowel to be targeted differentially. The infusions did not alter the consistency of the fecal pellets or induce defecation. Gas chromatography at various time points after butyrate infusion showed a small, but statistically insignificant, rise in fecal excretion, representing less than 10 percent of the infused butyrate. CONCLUSIONS: A highly reproducible in vivo rat model, with an experimental life span of five to six weeks, has been achieved. Biological agents can be accurately delivered via the colonic tubes and are retained in the colonic segment of interest. This intubation model should provide a valuable tool in the future for in vivo studies of colonic biology.

Animals↗
PubMed2002

Colonic epithelial atrophy induced by a fibre-free diet in rats is reversed by minimal amounts of luminal butyrate, but only in the short term.

BACKGROUND: Luminal butyrate may be trophic to the colonic epithelium, but this effect is poorly characterized. The aim of the present study was to define the dose-response, time-course, site-specificity and the dependence on background diet of the effects of butyrate on epithelial proliferation in normal distal colon, using an in vivo rat model of colonic substrate delivery. METHODS: Male Sprague-Dawley rats, maintained on a fibre-free diet, had butyrate infused twice daily into the colonic lumen via polyethylene tubes placed at laparotomy. Varying dose levels (0-80 micro mol/d; 4 d), site (caecal vs distal colonic), duration of infusions (1-5 weeks; 80 micro mol/d), or dietary fibre intake were investigated. Epithelial proliferative indices were assessed stathmokinetically. RESULTS: Four-day infusions of butyrate led to a progressive trophic effect (cells/crypt column increased from 37.9 +/- 1.6 at 0 micro mol/d to 44.7 +/- 1.2 at 80 micro mol/d) on fibre-deprived colonic mucosa, related linearly to the daily butyrate dose (P < 0.001, linear regression). This effect was mediated by increases in the number and proportion of mitoses, related to the square of the butyrate dose (P < 0.001 in each case, polynomial regression). Butyrate (80 micro mol/d) was associated with significantly higher cellularity (59.9 +/- 1.4) and mitotic activity (4.9 +/- 0.6) per crypt column compared to vehicle controls (50.3 +/- 1.6 and 0.9 +/- 0.2, respectively; P < 0.05, t-tests), at 1 and 3 weeks, but not at 5 weeks. Butyrate had similar effects on distal colonic crypt cellularity (62.0 +/- 1.5) when delivered caecally, but in rats fed a fibre-containing diet, colonic crypt cellularity (55.3 +/- 3.2) was similar to baseline (59.6 +/- 1.9). CONCLUSIONS: Trophic effects of butyrate are concentration-dependent and occur at low doses in the short term, but are not sustained over longer periods. They are seen only in a fibre-deprived state and appear to be independent of the site of administration.

Animals↗