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Biomedical subjects

Shimul A Shah

Publications and source records attributed to Shimul A Shah.

10 recordsLinked to original sources

Accuracy of staging as a predictor for recurrence after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Tumor number, size, and macrovascular invasion (MacroVI) are the most widely used predictors of survival after liver transplantation (LT) for hepatocellular carcinoma (HCC). We analyzed all patients undergoing LT for HCC at our center to establish the accuracy of preoperative clinical staging and to determine which patients have a higher probability of being understaged. METHODS: In all, 118 patients with confirmed HCC after LT from April 1991 to October 2004 at our institution were reviewed. All patients were monitored with serial imaging every 3 months to ensure their eligibility for LT within Milan criteria. Understaging in the 118 patients was defined as evidence on explant pathology that Milan criteria (TNM stage pT1 or pT2) had been exceeded. RESULTS: Five-year DFS was 78% with a recurrence rate of 15% after a median follow-up after LT of 30 months. On explant pathology, 43% (51/118) of patients exceeded Milan criteria and had a worse DFS (1 year, 95% vs. 87%; 3 year, 87% vs. 64%; P=0.03) compared to those who met LT criteria. Understaging was more likely in patients with imaging characteristics of > or = 2 tumor nodules (P=0.005) and tumor growth > 0.25 cm/month (P=0.02) and pathologic findings of vascular invasion (P=0.001) and bilobar tumors (P=0.002). CONCLUSIONS: Preoperative imaging every 3 months while on the waiting list frequently understages HCC as assessed by explant pathology. Recurrence after LT often occurred in patients that were understaged. Improving the accuracy of clinical staging and inclusion parameters will ensure proper organ allocation and acceptable outcomes after LT.

Adult↗

Surgical resection of hepatic and pulmonary metastases from colorectal carcinoma.

BACKGROUND: Patients with hepatic and pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. We examined the longterm outcomes of patients who underwent both lung and liver resections for colorectal metastases over a 10-year period. STUDY DESIGN: Four hundred twenty-three hepatectomies were performed for metastatic CRC between 1992 and 2002 at two university-affiliated hospitals. Patients who underwent both lung and liver resections for metastatic CRC were studied. Demographic, perioperative, and survival data were evaluated by retrospective chart review. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis and survival curves were compared using the log-rank test. RESULTS: Thirty-nine patients underwent both lung and liver resections for metastatic CRC. Eleven patients (28%) underwent staged liver and lung metastasectomy from synchronously identified metastases. Twenty-eight patients (72%) underwent sequential metastasectomy because of recurrent disease. The median disease-free and overall survivals after initial metastasectomy were 19.8 and 87 months, respectively. Serial metastasectomy was common in this patient population. The mean number of metastasectomies performed was 2.6 per patient (range 1 to 4). There was no difference in overall survival for patients with synchronous versus metachronous presentation of liver and lung metastases (p=0.45). The site of first recurrence after initial metastasectomy was, most commonly, the lung (n=19, 49%), followed by the liver (n=8, 21%). Nineteen patients (49%) underwent subsequent resections for recurrences. Seven patients (18%) underwent 2 or more liver resections for recurrent disease, and 12 (31%) underwent multiple lung resections. CONCLUSIONS: An aggressive multidisciplinary surgical approach should be undertaken for recurrent CRC metastases. In selected patients, serial metastasectomy for recurrent metastatic disease is safe and results in excellent longterm survival after CRC resection.

Adult↗

Adult-to-adult living donor liver transplantation.

The present review outlines the principles of living donor liver transplantation, donor workup, procedure and outcomes. Living donation offers a solution to the growing gap between the need for liver transplants and the limited availability of deceased donor organs. With a multidisciplinary team focused on donor safety and experienced surgeons capable of performing complex resection/reconstruction procedures, donor morbidity is low and recipient outcomes are comparable with results of deceased donor transplantation.

Adult↗

Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes.

BACKGROUND: Early recurrence (ER) (<1 year) after liver resection is one of the most important factors that impact the prognosis of patients with hepatocellular carcinoma (HCC). We sought to determine factors associated with ER of HCC and examine the outcomes thereafter. STUDY DESIGN: From March 2001 to June 2003, 56 patients underwent hepatic resection for HCC at University of Toronto and were prospectively followed with median followup of 24 months. Patients with ER were compared with those who remained disease free for more than 1 year. Patient characteristics, tumor stage, and operative procedures were evaluated for their prognostic significance by univariate and multivariable analysis. Time to recurrence and time to death were analyzed using Kaplan-Meier survival curves and compared using log-rank analysis. RESULTS: The initial procedure in all patients was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained disease free for more than 1 year, and 4 (7%) were omitted from evaluation because of early (<30 days) death. Median survival after initial hepatic resection for those with ER was 27 months, and 2-year survival was 54%. There were no deaths in the group that remained disease free for more than 1 year (100% 2-year survival, p < 0.05). By multivariate analysis, vascular invasion and positive microscopic margins were significant predictors when all 4 variables were considered in the model (p < 0.05). After ER, 11 of 21 patients (52%) underwent additional therapy with significant improvement in median survival (33 months) compared with those not eligible for conventional therapy (18 months, p = 0.05). CONCLUSIONS: ER after liver resection for HCC is the leading cause of death during the first 2 years after potentially curative resection. ER will develop in approximately 75% of patients with either vascular invasion or positive margins. For patients with these predictive factors additional treatment might be advised.

Adult↗

Predictors of failure after pancreaticoduodenectomy for ampullary carcinoma.

BACKGROUND: Complete resection offers the only potential cure for ampullary carcinoma. We analyzed factors that contribute to treatment failure and survival in patients who underwent pancreaticoduodenectomy for ampullary carcinoma. STUDY DESIGN: We retrospectively reviewed all patients who underwent pancreaticoduodenectomy between August 1994 and August 2003 for ampullary carcinoma. Demographic, clinical, and pathologic data were collected. Chi-square analysis was used for categorical data and the t-test was used for continuous variables. Kaplan-Meier analyses were compared using the log-rank test to examine patient survival. RESULTS: Forty-three patients (24 men) aged 63.7 +/- 11.4 years (standard deviation) were followed for a mean of 23.9 months (median 660 days, range 18 to 2,249 days). Jaundice (n = 33) and weight loss (n = 13) were the most common presenting symptoms. Stage (p < 0.01) and degree of differentiation (p < 0.029) were significant predictors of failure by univariate analysis. But only stage (p < 0.04) was a significant predictor by multivariate analysis. Further analysis revealed that nodal status (p < 0.001), but not tumor grade, was a significant predictor of treatment failure. Neither demographic nor clinical variables were significant predictors. Five-year overall and disease-free survival rates were 67.4% and 51.4%, respectively. Both metastases and disease recurrence had significant impact on patient survival. CONCLUSIONS: Tumor stage is associated with treatment failure after pancreaticoduodenectomy for ampullary carcinoma and may identify candidates for adjuvant therapy. Because an aggressive surgical approach can be adopted safely with the best chance for cure, we recommend that pancreaticoduodenectomy be offered to all patients with ampullary tumors when malignancy or dysplasia is in question.

Adenocarcinoma↗

Analysis and outcomes of right lobe hepatectomy in 101 consecutive living donors.

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6-55 years); median follow-up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Clavien's classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.

Adult↗

Rectal complications after prostate brachytherapy.

PURPOSE: Prostate brachytherapy is gaining wide popularity as an alternative to resection for the treatment of locally advanced prostate cancer. Rectal-urethral fistula after prostate brachytherapy is a rare but serious complication, and its incidence, presentation, risk factors, and clinical management have not been well described. METHODS: From January 1997 to October 2002, seven patients with rectal-urethral fistulas were referred to two institutions (Brigham and Women's Hospital and West Roxbury Veteran's Administration Hospital) of a major teaching referral center. Clinical presentation, risk factors, prostate staging, and clinical management were examined in a retrospective fashion. RESULTS: Seven rectal-urethral fistulas developed from roughly 700 (1 percent) patients treated with prostate brachytherapy for prostate cancer. The average patient age was 67.7 years, preimplant prostate-specific antigen was 7.1, and Gleason score was 3+3. Symptoms occurred at a mean of 27.3 months after prostate brachytherapy was started and included anorectal pain (57 percent), clear mucous discharge (57 percent), diarrhea (43 percent), and rectal ulceration (43 percent). Coronary artery disease was a common comorbidity (71 percent). Previous transurethral resection of prostate (28 percent) and pelvic irradiation or external beam radiation therapy (14 percent) were not associated with increased risk of rectal-urethral fistula. All patients underwent a diverting colostomy (86 percent) or ileostomy (14 percent), and four patients went on to have definitive therapy. Definitive resection was performed between 5 and 43 months after diverting ostomy and was chosen on the basis of comorbid disease, quality of life, and degree of operation. Two patients required a second diversion after definitive resection because of anorectal pain and a colocutaneous fistula. Postoperative complications included myocardial infarction (14 percent), blood transfusion (14 percent), and bowel perforation (14 percent). Patients became symptom-free nine months after surgery. Six patients are alive and well today; one died from an unrelated cause. CONCLUSIONS: Rectal-urethral fistula after prostate brachytherapy is a rare but devastating complication. Patients should be followed for at least three years after prostate brachytherapy because symptoms can develop late in the course. Although diversion of fecal stream does not heal the fistula, all patients diagnosed with rectal-urethral fistula should first undergo diverting ostomy to alleviate symptoms. Then, one should consider definitive resection and ostomy closure.

Aged↗

Regulation of NFkappaB in hepatic ischemic preconditioning.

BACKGROUND: The second messengers tyrosine kinase (TK) and protein kinase C (PKC) have been implicated in mediating the cellular signaling cascade during hepatic ischemic preconditioning (IPC). We evaluated the role of TK and PKC on the modulation of the transcription factor nuclear factor kappa B (NFkappaB) and its inhibitor IkappaB alpha during IPC. STUDY DESIGN: Yorkshire pigs underwent routine harvest. IPC livers underwent 15 minutes of ischemia and 15 minutes of in situ perfusion before harvest, with or without pretreatment with a TK inhibitor (genistein) or a PKC inhibitor (chelerythrine). During cold storage and reperfusion, tissue extracts were analyzed for IkappaB alpha phosphorylation and NFkappaB levels and for TK and PKC activity by Western blot. RESULTS: Control pig livers demonstrated no change in the levels of TK, PKC, IkappaB alpha, or NFkappaB before cold ischemia. IPC grafts demonstrated activation of TK and PKC with increased IkappaB alpha phosphorylation and NFkappaB levels before cold ischemia. IPC grafts pretreated with genistein demonstrated inhibition of TK activation but not of PKC activation. Genistein-pretreated grafts also demonstrated inhibition of IkappaB alpha phosphorylation and a lack of NFkappaB translocation to the nucleus throughout the entire experiment. IPC grafts pretreated with chelerythrine demonstrated inhibition of PKC activation but not TK activation. Chelerythrine-pretreated grafts also demonstrated IkappaB alpha phosphorylation before cold ischemia and enhanced nuclear levels of NFkappaB. CONCLUSIONS: Data suggest that the role of TK in IPC might be mediated in part by NFkappaB, but PKC does not depend on NFkappaB for its effect. Two parallel signaling pathways might explain these data.

Alkaloids↗

Small bowel varices from neuroendocrine tumor of the pancreas.

Small bowel varices (SBVs) are a rare but important cause of gastrointestinal (GI) bleeding. We present a case of SBVs caused by superior mesenteric vein thrombosis from a large neuroendocrine tumor of the pancreas. This patient presented with GI bleeding. A computed tomography scan showed an incidental hypervascular mass that was unresectable. After exhaustive work-up, the GI bleeding was in fact due to the mass by direct compression on the superior mesenteric vein. The SBVs were evident on the venous phase of a computed tomography angiogram. The patient was treated medically with octreotide, beta-blockade, and external beam radiation therapy applying the physiology of esophagogastric varices to the small bowel. Persistent GI bleeding in the presence of a large central mass should always alert one to consider varices from collateral flow as a possible cause.

Aged, 80 and over↗