Attila Nakeeb

Cystic pancreatic neoplasms: observe or operate.

Objective:The objectives of this analysis were to define the incidence, natural history, and predictors of neoplasia in pancreatic cysts to determine which patients can safely be observed and which should undergo an operation. Summary Background Data:With advancements in imaging technology, cystic lesions of the pancreas are being detected with increased frequency. Many of these lesions are small and asymptomatic, but they may be associated with pancreatitis or have malignant potential. Therefore, the management of these patients is complex, and knowledge of pancreatic cyst natural history and predictors of neoplasia are important. Methods:From January 1995 through December 2002, all radiologic, surgical, and pathology records were reviewed for the presence of pancreatic cysts. In determining natural history, only patients with 2 scans more than 1 month apart at our institution were included. Patients with a clinical history and laboratory evidence of pancreatitis and/or pathologic confirmation of a pseudocyst were excluded. Factors analyzed as potential predictors of neoplasia included age, gender, cyst size, and symptoms. Serous cystadenomas, solid and cystic papillary (Hamoudi) tumors, lymphoepithelial cysts and simple cysts were all benign, whereas mucinous cystic neoplasms, intraductal papillary mucinous neoplasm, cystic neuroendocrine tumors, and cystadenocarcinomas were considered to be premalignant or malignant. Results:Among 24,039 CT or MR scans, 290 patients (1.2%) had pancreatic cysts, and 168 of these patients (0.7%) had no documentation of pancreatitis. Seventy-nine of these patients with 103 cysts had more than 1 scan with an average interval of 16 months. These cysts increased in size in 19%, did not change in 59% and decreased in 22% of patients. Forty-nine patients underwent surgery for 14 benign (serous cystadenomas = 10, Hamoudi = 2, lymphoepithelial = 1, simple = 1) 25 premalignant (mucinous cystic neoplasm =16, intraductal papillary mucinous neoplasm = 5, neuroendocrine tumors = 4), or 10 malignant (intraductal papillary mucinous neoplasm = 7, cystadenocarcinomas = 3) lesions. Gender and cyst size did not predict neoplasia. However, presence of symptoms predicted premalignant or malignant pathology (60% vs. 23%, P < 0.05), and age over 70 years was associated with malignancy (60% vs. 21%, P < 0.02). Conclusions:These data suggest that cystic pancreatic neoplasms 1) occur in 0.7% of patients, 2) increase in 19% over 16 months, and 3) are likely (60%) to be malignant in patients older than 70 years. Therefore, we recommend surgical excision for pancreatic cysts that are increasing under observation, symptomatic, or detected radiologically in fit older patients.

Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches.

Objectives:To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. Summary and Background Data:LLP is being performed more commonly with limited data comparing results with outcomes from OLP. Methods:Data from 8 centers were combined for all cases performed between 2002–2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. Results:Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19–0.56). Conclusions:In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.

Perihilar cholangiocarcinoma: Postoperative radiotherapy does not improve survival

ObjectiveThe aims of this analysis were to determine prospectively the effects of surgical resection and radiation therapy on the length and quality of survival as well as late toxicity in patients with perihilar cholangiocarcinoma. BackgroundRetrospective analyses have suggested that adjuvant radiation therapy improves survival in patients with perihilar cholangiocarcinoma. However, in these reports, patients receiving radiotherapy tended to have smaller, often resectable tumors, and were relatively fit. In comparison, patients who have not received radiotherapy often had unresectable tumors, metastatic disease, or poor performance status. MethodsFrom 1988 through 1993, surgically staged patients with perihilar cholangiocarcinoma and 1) no evidence of metastatic disease, 2) Karnofsky score >60,3) no prior malignancy or radiotherapy, and 4) a patent main portal vein were analyzed. Fifty patients were stratified by resection (n = 31) versus operative palliation (n = 19) and by radiation (n = 23) versus no radiotherapy (n = 27). ResultsPatients undergoing resection had smaller tumors (1.9 ± 2.8 vs. 2.4 ± 2.1 cm, p < 0.01) that were less likely to invade the hepatic artery (3% vs. 42%, p < 0.05) or portal vein (6% vs. 53%, p < 0.05). Multiple parameters that might have affected outcome were similar between patients who did and did not receive radiation therapy. Resection improved the length (24.2 ± 2.5 vs. 11.3 ± 1.0 months, p < 0.05) and quality of survival. Radiation had no effect on the length (18.4 ± 2.9 vs. 20.1 ± 2.4 months) or quality of survival or on late toxicity. ConclusionsThis analysis suggests that in patients with localized perihilar cholangiocarcinoma, resection prolongs survival whereas radiation has no effect on either survival or late toxicity. Thus, new agents or strategies to deliver adjuvant therapy are needed to improve survival in these patients.

A Multicenter Analysis of Distal Pancreatectomy for Adenocarcinoma: Is Laparoscopic Resection Appropriate?

BACKGROUND As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. STUDY DESIGN Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and long-term (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. RESULTS There were 212 patients who underwent DP for PDAC; 23 (11%) of these were approached laparoscopically. For all 212 patients, 56 (26%) had positive margins. The mean number of nodes (+/- SD) examined was 12.6 +/-8.4 and 114 patients (54%) had at least 1 positive node. Median overall survival was 16 months. In the matched analysis there were no significant differences in positive margin rates, number of nodes examined, number of patients with at least 1 positive node, or overall survival. Logistic regression for all 212 patients demonstrated that advanced age, larger tumors, positive margins, and node positive disease were independently associated with worse survival; however, method of resection (ODP vs. LDP) was not. Hospital stay was 2 days shorter in the matched comparison, which approached significance (LDP, 7.4 days vs. ODP, 9.4 days, p = 0.06). CONCLUSIONS LDP provides similar short- and long-term oncologic outcomes as compared with OD, with potentially shorter hospital stay. These results suggest that LDP is an acceptable approach for resection of PDAC of the left pancreas in selected patients.

Fatty pancreas: A factor in postoperative pancreatic fistula

Objective:To determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have pancreatic fat than matched controls. Background:Pancreatic fistula continues to be a major cause of postoperative morbidity and increased length of stay after pancreatoduodenectomy. Factors associated with postoperative pancreatic fistula include a soft pancreas, a small pancreatic duct, the underlying pancreatic pathology, the regional blood supply, and surgeons experience. Fatty pancreas previously has not been considered as a contributing factor in the development of postoperative pancreatic fistula. Methods:Forty patients with and without a pancreatic fistula were identified from an Indiana University database of over 1000 patients undergoing pancreatoduodenectomy and matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation. Surgical pathology specimens from the pancreatic neck were reviewed blindly for fat, fibrosis, vessel density, and inflammation. These parameters were scored (0–4+). Results:The pancreatic fistula patients were less likely (P < 0.05) to have diabetes but had significantly more intralobular (P < 0.001), interlobular (P < 0.05), and total pancreatic fat (P < 0.001). Fistula patients were more likely to have high pancreatic fat scores (50% vs. 13%, P < 0.001). Pancreatic fibrosis, vessel density, and duct size were lower (P < 0.001) in the fistula patients and negative correlations (P < 0.001) existed between fat and fibrosis (R = −0.40) and blood vessel density (R = −0.15). Conclusions:These data suggest that patients with postoperative pancreatic fistula have (1) increased pancreatic fat and (2) decreased pancreatic fibrosis, blood vessel density, and duct size. Therefore, we conclude that fatty pancreas is a risk factor for postoperative pancreatic fistula.

CT vs MRCP: optimal classification of IPMN type and extent.

IntroductionIntraductal papillary mucinous neoplasms (IPMNs) of the pancreas are being diagnosed with increased frequency. CT scanning commonly serves as the primary imaging modality before surgery. We hypothesized MRCP provides better characterization of IPMN type/extent, which more closely matches actual pathology.MethodsOf 214 patients treated with IPMN (1991–2006), 30 had both preoperative CT and MRCP. Of these, 18 met imaging study criteria. Independent readers performed retrospective, blinded analyses using standardized criteria for IPMN type and extent.ResultsA ductal connection was detected on 73% of MRCP scans and only 18% of CT. IPMN type was classified differently in seven (39%); four (22%) of which were read on CT as having main duct involvement where this was not appreciated on MRCP or found on surgical pathology. MRCP showed multifocal disease in 13(72%) versus only 9(50%) on CT. A different disease distribution was seen in 9(50%). Finally, 101 branch lesions were identified on MRCP compared to 46 on CT.ConclusionsCT falls short of MRCP in detecting a ductal connection, estimating main duct involvement, and identification of small branch duct cysts. These factors influence diagnostic accuracy, cancer risk stratification and operative strategy. MRCP should be employed for optimal management of patients with IPMN.

A Randomized Prospective Multicenter Trial of Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage

Objective:To test by randomized prospective multicenter trial the hypothesis that pancreaticoduodenectomy (PD) without the use of intraperitoneal drainage does not increase the frequency or severity of complications. Background:Some surgeons have abandoned the use of drains placed during pancreas resection. Methods:We randomized 137 patients to PD with (n = 68, drain group) and without (n = 69, no-drain group) the use of intraperitoneal drainage and compared the safety of this approach and spectrum of complications between the 2 groups. Results:There were no differences between drain and no-drain cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, baseline quality of life, or operative technique. PD without intraperitoneal drainage was associated with an increase in the number of complications per patient [1 (0-2) vs 2 (1-4), P = 0.029]; an increase in the number of patients who had at least 1 ≥grade 2 complication [35 (52%) vs 47 (68%), P = 0.047]; and a higher average complication severity [2 (0-2) vs 2 (1-3), P = 0.027]. PD without intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess (10% vs 25%, P = 0.027), severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. The Data Safety Monitoring Board stopped the study early because of an increase in mortality from 3% to 12% in the patients undergoing PD without intraperitoneal drainage. Conclusions:This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

Gallstones: Genetics Versus Environment

ObjectiveThe aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. Summary Background DataGallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. MethodsA gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. ResultsIn the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P < .003), obesity (BMI > 30, relative risk 3.7, P < .001), age > 50 (relative risk 2.5, P < .001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P < .01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P < .02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. ConclusionsThese data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

Renal Cell Carcinoma Metastatic to the Pancreas: Results of Surgical Management

Metastatic tumors to the pancreas are uncommon. Renal cell carcinoma is one of the few tumors known to metastasize to the pancreas. The purpose of the current report is to evaluate the surgical management and long-term outcome of patients with metastatic renal cell carcinoma. A retrospective review of patients undergoing pancreatic resection for renal cell carcinomas metastatic to the pancreas or periampullary region between April 1989 and May 1999, inclusive, was performed. Time from initial presentation, other metastatic sites, surgical outcomes, and long-term survival were evaluated. During the 10-year time period, 10 patients underwent pancreatic resection for renal cell carcinoma metastases. Ofthose, six underwent pancreaticoduodenectomy and two underwent distal pancreatectomy, whereas the two remaining patients underwent total pancreatectomy for extensive tumor involvement throughout the entire gland. The mean time from nephrectomy for resection of the primary tumor to reoperation for periampullary recurrence was 9.8 years (median 8.5 years). The range was 0 to 28 years, with one patient presenting with a synchronous metastasis. The mean age of the patients was 61.2 years with 60% of patients being male and 90% being white. Pathologic findings included histologically negative lymph nodes and negative surgical margins in all patients. One patient had tumor involving the retroperitoneal soft tissue, but final margins were negative. The mean live patient follow-up was 30 months (median =1.5 months), with eight patients remaining alive. The Kaplan-Meier actuarial 5-year survival was 75%, with the longest survivor still alive 117 months following resection. The patient with retroperitoneal soft tissue involvement died 4 months after resection. The pancreas is an uncommon site of metastasis for renal cell carcinoma, typically occurring years after treatment of the primary tumor. When the metastatic focus is isolated and the tumor can be resected in its entirety, patients can experience excellent S-year survival rates. The current report suggests that pancreatic metastases from renal cell carcinoma should be managed aggressively with complete resection when possible.

Correlation of CT Enteroclysis With Surgical Pathology in Crohn's Disease

BACKGROUND:The response to therapy in Crohns disease (CD) depends on the inflammatory or fibrostenotic nature of the underlying pathological process. Standard diagnostic tests cannot reliably distinguish between these two entities. Although CT enteroclysis (CTE) has shown promise in the evaluation of small bowel disorders, its accuracy for the differentiation of CD phenotypes is unknown.AIMS:To determine the accuracy of CTE compared with surgical pathology in patients with CD and to assess the association of CTE variables with inflammatory or fibrostenotic pathological lesions.METHODS:CTE studies from patients who underwent resective bowel surgery for CD were reviewed and compared with the pathological specimens using a standardized scoring system. Patients were excluded if they had incomplete studies, nonresective surgeries, or a diagnosis of malignancy. CTE variables, such as mucosal and mural enhancement, wall thickness, engorgement of vasa recta (comb sign), adenopathy, and the presence and severity of strictures were compared with the pathology results using Mantel-Haenszel χ2, Spearmans rank coefficient, and logistic regression analyses.RESULTS:Of the 54 patients enrolled, 10 were excluded. The remaining patients (61% female, 84% white) underwent 44 surgical interventions generating 47 bowel segments that were included in the analysis. The indications for surgery were: bowel obstruction in 21; perforating disease in 13; and refractory, nonobstructive disease in 15. The accuracy of CTE for inflammatory and fibrostenotic lesions was 76.6% and 78.7% using a four- and three-point grading system, respectively. There was good correlation between CTE and pathology in regards to inflammation (Spearmans r = 0.7, P < 0.0001) and fibrostenosis (Spearmans r = 0.6, P < 0.0001) scores. The pathological inflammation score was significantly associated with the CTE variables mucosal enhancement, wall thickness, comb sign, and adenopathy (Mantel-Haenszel χ2 P values 0.04, 0.04, <0.0001, and 0.016, respectively). The pathological fibrostenosis score was significantly associated with the presence and severity of stenosis on CTE (P = 0.001 and 0.007, respectively). By logistic regression analysis, the strongest association was seen with the comb sign (OR 5.52, P < 0.001) for inflammation and the presence of stenosis (OR 5.87, P = 0.006) for fibrostenosis. There was no interaction between the time interval from CTE to surgery and the strength of these associations.CONCLUSIONS:CTE may reliably differentiate between inflammatory and fibrostenotic lesions and may have an important role in the management of CD. Specific CTE variables correlate with each of these phenotypes and deserve further investigations in prospective studies.