Flavio G. Rocha

Intraductal papillary neoplasm of the bile duct: A biliary equivalent to intraductal papillary mucinous neoplasm of the pancreas?

Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma characterized by intraductal growth and better outcome compared with the more common nodular‐sclerosing type. IPNB is a recognized precursor of invasive carcinoma, but its pathogenesis and natural history are ill‐defined. This study examines the clinicopathologic features and outcomes of IPNB. A consecutive cohort of patients with bile duct cancer (hilar, intrahepatic, or distal) was reviewed, and those with papillary histologic features identified. Histopathologic findings and immunohistochemical staining for tumor markers and for cytokeratin and mucin proteins were used to classify IPNB into subtypes. Survival data were analyzed and correlated with clinical and pathologic parameters. Thirty‐nine IPNBs were identified in hilar (23/144), intrahepatic (4/86), and distal (12/113) bile duct specimens between 1991 and 2010. Histopathologic examination revealed 27 pancreatobiliary, four gastric, two intestinal, and six oncocytic subtypes; results of cytokeratin and mucin staining were similar to those of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Invasive carcinoma was seen in 29/39 (74%) IPNBs. Overall median survival was 62 months and was not different between IPNB locations or subtypes. Factors associated with a worse median survival included presence and depth of tumor invasion, margin‐positive resection, and expression of MUC1 and CEA. Conclusion: IPNBs are an uncommon variant of bile duct cancer, representing approximately 10% of all resectable cases. They occur throughout the biliary tract, share some histologic and clinical features with IPMNs of the pancreas, and may represent a carcinogenesis pathway different from that of conventional bile duct carcinomas arising from flat dysplasia. Given their significant risk of harboring invasive carcinoma, they should be treated with complete resection. (HEPATOLOGY 2012)

The Blumgart Preoperative Staging System for Hilar Cholangiocarcinoma: Analysis of Resectability and Outcomes in 380 Patients

BACKGROUNDnComplete resection of hilar cholangiocarcinoma (HCCA) is a critical determinant of long-term survival. This study validates a previously reported preoperative clinical T staging system for determining resectability of HCCA.nnnSTUDY DESIGNnConsecutive patients with confirmed HCCA treated over an 18-year period were included. Patient demographics, preoperative imaging studies, resection type, margin status, lymph node status, histopathologic findings, morbidity, and outcomes were entered prospectively and analyzed retrospectively; changes in these variables over time were assessed. All patients were placed into 1 of 3 stages based on the extent of ductal involvement by tumor, portal vein compromise, or lobar atrophy.nnnRESULTSnFrom March 1991 through December 2008, 380 patients were evaluated. Eighty-five patients had unresectable disease; 295 patients underwent exploration with curative intent. One hundred fifty-seven patients underwent resection: 129 (82.2%) had a concomitant hepatic resection and 120 (76.4%) had an R0 resection. Of the 32 actual 5-year survivors (120 at risk), 30 patients (93.8%) had a concomitant hepatic resection. In patients who underwent an R0 resection, concomitant partial hepatectomy, well-differentiated histology, and negative lymph nodes were independent predictors of long-term survival. In the 376 patients whose disease could be staged, the preoperative clinical T staging system predicted resectability (p < 0.001), metastatic disease (p < 0.001), and R0 resection (p = 0.007).nnnCONCLUSIONSnThe preoperative clinical T staging system of Blumgart, defined by the radial and longitudinal tumor extent, accurately predicts resectability of HCCA. The full outcomes benefit of resection is realized only if a concomitant partial hepatectomy is performed.

Hilar cholangiocarcinoma: the Memorial Sloan-Kettering Cancer Center experience.

Background/purposeHilar cholangiocarcinoma (HCCA) is a rare cancer with a low resectability rate, frequent recurrence after resection and an overall poor outcome. It is widely accepted that en bloc partial hepatectomy is a necessary part of the surgical therapy, but controversy surrounds other areas, including extent of lymphadenectomy and preoperative use of biliary drainage of the future liver remnant (FLR). This study analyzes the authors’ experience with HCCA, emphasizing outcome after resection in a more recent cohort.MethodsAll patients with HCCA evaluated at Memorial Sloan-Kettering Cancer Center (MSKCC) since 1991 were included in the initial analysis. Outcome after resection was specifically assessed in patients submitted to operation between January 2001 and September 2008. Patient demographics, preoperative evaluation, resection type, margin status, lymph node status, complications, morbidity and survival were examined. Preoperative disease staging was performed in all patients according to the Blumgart classification. Separate analyses were conducted to assess the impact of preoperative biliary drainage on the FLR and the optimal lymph node harvest. Outcomes for resected patients were analyzed by Fisher’s exact test and log rank tests.ResultsThree hundred and fifty-two patients with HCCA were evaluated since 1991, of which 118 were seen between 2001 and 2008. During this latter period, 105 (89%) patients underwent exploration, and of the 60 patients that underwent resection with curative intent, 48 (80%) had R0 resections. There were 3 perioperative deaths (5%), and 22 (28%) patients had complications. Patients with an R0 resection had the highest disease-specific survival followed by those with R1 resection when compared to unresected patients. The median follow-up period was 18xa0months. Classification by the Blumgart preoperative staging system predicted resectability and the likelihood of R0 resection. The benefit of pre-operative biliary drainage of the FLR appeared to be limited to patients with a predicted FLR volume of <30%. In patients with node-negative tumors, survival was greater in those with more than 7 lymph nodes harvested.ConclusionsR0 resection including hepatectomy with negative lymph nodes is feasible in the majority of patients with resectable HCCA. This strategy is associated with a prolonged disease-specific survival.

Extended Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer Demonstrates Promising Postoperative Outcomes and Survival

BackgroundThe optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined. Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head.MethodsPatients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospectively maintained registry. Included patients were initiated on a 24-week course of neoadjuvant chemotherapy. Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent. Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed.ResultsSixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy. Thirty-nine (61xa0%) met resection criteria and underwent operative exploration with curative intent, and 31 (48xa0%) were resected. Of the resected patients, 18 (58xa0%) had positive lymph nodes, 15 (48xa0%) required en-bloc venous resection, 27 (87xa0%) had a R0 resection, and 3 (10xa0%) had a complete pathologic response. There were no postoperative deaths at 90xa0days, 16xa0% of patients had a severe complication, and the 30-day readmission rate was 10xa0%. The median overall survival of all 64 patients was 23.6xa0months, whereas that of unresectable patients was 15.4xa0months. Twenty-five of the resected patients (81xa0%) are still alive at a median follow-up of 21.6xa0months.ConclusionsExtended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma, selects a subset of patients for curative surgery with low perioperative morbidity, and is associated with favorable survival.

A Novel Survival-Based Tissue Microarray of Pancreatic Cancer Validates MUC1 and Mesothelin as Biomarkers

Background One–fifth of patients with seemingly ‘curable’ pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed ‘unresectable’ by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046). Methods and Findings Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term (cancer-specific death <12 months, nu200a=u200a58) and long-term survivors (>30 months, nu200a=u200a79) who underwent resection for PDA (total, nu200a=u200a137). The s-TMA functions as a biological filter to identify bona fide prognostic markers associated with survival group extremes (at least 18 months separate survival groups). Based on a stringent selection process, 13 putative PDA biomarkers were identified from the public biomarker repository. Candidates were tested against the s-TMA by immunohistochemistry to identify the best markers of tumor biology. In a multivariate model, MUC1 (odds ratio, ORu200a=u200a28.95, 3+ vs. negative expression, pu200a=u200a0.004) and MSLN (ORu200a=u200a12.47, 3+ vs. negative expression, pu200a=u200a0.01) were highly predictive of early cancer-specific death. By comparison, pathologic factors (size, lymph node metastases, resection margin status, and grade) had ORs below three, and none reached statistical significance. ROC curves were used to compare the four pathologic prognostic features (ROC areau200a=u200a0.70) to three univariate molecular predictors (MUC1, MSLN, MUC2) of survival group (ROC areau200a=u200a0.80, pu200a=u200a0.07). Conclusions MUC1 and MSLN were superior to pathologic features and other putative biomarkers as predicting survival group. Molecular assays comparing cancers from short and long survivors are an effective strategy to screen biomarkers and prioritize candidate cancer genes for diagnostic and therapeutic studies.

Dual-modality drainage of infected and symptomatic walled-off pancreatic necrosis: long-term clinical outcomes

BACKGROUNDnManagement options for symptomatic and infected walled-off pancreatic necrosis (WOPN) have evolved over the past decade from open surgical necrosectomy to more minimally invasive approaches. We reported the use of a combined percutaneous and endoscopic approach (dual modality drainage [DMD]) for the treatment of symptomatic and infected WOPN, with good short-term outcomes in a small cohort of patients.nnnOBJECTIVEnTo describe the long-term outcomes of 117 patients with symptomatic and infected WOPN treated by DMD.nnnDESIGNnReview of a prospective, internal review board-approved database.nnnSETTINGnSingle, North American, tertiary-care center.nnnPATIENTSnAll patients with symptomatic and infected WOPN treated by DMD at our institution between 2007 and 2012.nnnINTERVENTIONnDMD of symptomatic and infected WOPN.nnnMAIN OUTCOME MEASUREMENTSnDisease-related mortality, pancreaticocutaneous fistula formation, need for early and late surgical intervention, procedure-related adverse events.nnnRESULTSnA total of 117 patients underwent DMD for symptomatic and infected WOPN. A total of 103 have completed treatment, with all percutaneous drains removed. Ten patients are still undergoing treatment, and 4 patients died with percutaneous drains in place (3.4% disease-related mortality). For the patients completing therapy, the median duration of follow-up was 749.5 days. No patients required surgical necrosectomy or surgical treatment of DMD-related adverse events; 3 patients required late surgery for pain (n = 2) and gastric outlet obstruction (n = 1). There were no procedure-related deaths. In patients who have completed treatment, percutaneous drains have been removed in 100%; no patients have developed pancreaticocutaneous fistulas.nnnLIMITATIONSnSingle-center design, lack of a comparison group.nnnCONCLUSIONnDMD for symptomatic and infected WOPN results in favorable clinical outcomes; complete avoidance of pancreaticocutaneous fistulae, surgical necrosectomy, and major procedure-related adverse events, while maintaining single-digit disease-related mortality.

Patterns of Recurrence After Ablation of Colorectal Cancer Liver Metastases

PurposeTo determine the local recurrence rate and factors associated with recurrence after intraoperative ablation of colorectal cancer liver metastases.MethodsA retrospective analysis of a prospectively maintained database was performed for patients who underwent ablation of a hepatic colorectal cancer metastasis in the operating room from April 1996 to March 2010. Kaplan-Meier survival curves and Cox models were used to determine recurrence rates and assess significance.ResultsAblation was performed in 10% (nxa0=xa0158 patients) of all cases during the study period. Seventy-eight percent were performed in conjunction with a liver resection. Of the 315 tumors ablated, most tumors were ≤1xa0cm in maximum diameter (53%). Radiofrequency ablation was used to treat most of the tumors (70%). Thirty-six tumors (11%) had local recurrence as part of their recurrence pattern. Disease recurred in the liver or systemically after 212 tumors (67%) were ablated. On univariate analysis, tumor size greater than 1xa0cm was associated with a significantly increased risk of local recurrence (hazard ratio 2.3, 95% confidence interval 1.2–4.5, Pxa0=xa00.013). The 2xa0year ablation zone recurrence-free survival was 92% for tumors ≤1xa0cm compared to 81% for tumors >1xa0cm. On multivariate analysis, tumor size of >1xa0cm, lack of postoperative chemotherapy, and use of cryotherapy were significantly associated with a higher local recurrence rate.ConclusionsIntraoperative ablation appears to be highly effective treatment for hepatic colorectal tumors ≤1xa0cm.

Up and down or side to side? A systematic review and meta-analysis examining the impact of incision on outcomes after abdominal surgery

BACKGROUNDnThe aim of this study was to examine whether midline, paramedian, or transverse incisions offer potential advantages for abdominal surgery.nnnDATA SOURCESnWe searched MEDLINE, Embase, Web of Science, and The Cochrane Central Register of Controlled Trials from 1966 to 2009 for randomized controlled trials comparing incision choice.nnnMETHODSnWe systematically assessed trials for eligibility and validity and extracted data in duplicate. We pooled data using a random-effects model.nnnRESULTSnTwenty-four studies were included. Transverse incisions required less narcotics than midline incisions (weighted mean difference = 23.4 mg morphine; 95% confidence interval [CI], 6.9 to 39.9) and resulted in a smaller change in the forced expiratory volume in 1 second on postoperative day 1 (weighted mean difference = -6.94%; 95% CI, -10.74 to -3.13). Midline incisions resulted in higher hernia rates compared with both transverse incisions (relative risk = 1.77; 95% CI, 1.09 to 2.87) and paramedian incisions (relative risk = 3.41; 95% CI, 1.02 to 11.45).nnnCONCLUSIONSnBoth transverse and paramedian incisions are associated with a lower hernia rate than midline incisions and should be considered when exposure is equivalent.

Treatment of liver colorectal metastases: role of laparoscopy, radiofrequency ablation, and microwave coagulation.

Up to 50% of patients with colorectal cancer will develop metastatic disease in the liver. While surgical extirpation remains the best option for long‐term survival, several complementary modalities such as laparoscopy, radiofrequency ablation, and microwave coagulation have gained wide acceptance as primary and adjunct therapies for both resectable and unresectable disease. This review will focus on the application and outcome of these techniques in patients with colorectal liver metastases. J. Surg. Oncol. 2010;102:968–974.

Posterior 'Superior Mesenteric Artery First' Approach for Resection of Locally Advanced Pancreatic Cancer

BackgroundEn bloc resection of the superior mesenteric vein (SMV), portal vein (PV), and/or splenic vein (SV) with concomitant venous reconstruction is required in 11–65xa0% of cases of locally advanced pancreatic cancer.1 Early retropancreatic dissection of the superior mesenteric artery (SMA) from behind the pancreatic head utilizing an ‘artery first’ approach has been reported to be an efficient and safe approach to pancreaticoduodenectomy when SMA involvement is suspected.2 Additionally, this technique has been shown to reduce blood loss and result in shorter PV clamp times.3 While there are multiple variations to ‘artery first’ resection,4 this video will illustrate the critical steps of using the ‘posterior approach’ in patients with locally advanced pancreatic cancer. This approach has the benefit of early identification of a replaced right hepatic artery, but may be difficult in obese patients or those with extensive peripancreatic inflammation. These difficulties may be overcome by utilizing an ‘inferior supracolic (anterior) approach’, but this necessitates early division of the pancreatic neck and stomach.5MethodsSelect video clips were compiled from several pancreatoduodenectomies to demonstrate this technique. A variety of bipolar devices were utilized for dissection depending on surgeon preference. All patients were diagnosed with locally advanced pancreatic cancer by Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology (AHPBA/SSO) consensus criteria, confirmed by biopsy, and completed neoadjuvant chemotherapy. Patients were restaged by pancreas protocol computed tomography scan at the end of chemotherapy and offered local resection if the tumor did not progress and they were medically fit. No Institutional Review Board approval was required.ResultsThe operation begins by dividing the attachment of the transverse mesocolon to the right perinephric area and extending this down to the white line of Toldt, followed by a wide Kocher maneuver. The lateral attachments to the pancreatic head are then divided, thereby exposing the left renal vein. The lesser sac is entered directly over the uncinate, allowing for a full visceral rotation of the pancreatic head, and further facilitating exposure of the left renal vein. In the setting of malignancy, the SMA may now be palpated posterior to the pancreatic head and/or neck to confirm it is free of tumor. If tumor is invading the SMA, the pancreaticoduodenectomy is aborted prior to performing any gastrointestinal or pancreatic transections. If the SMA is free, the dissection is then carried on to the inferior aspect of the pancreatic neck. Here the SMV (jejunal and ileal branches), middle colic vein, and the gastroepiploic vein are identified and the latter is ligated and transected. Following this, dissection of the portal structures (hepatic arteries, gastroduodenal artery, common bile duct, and PV) is performed. The jejunum is then divided, the ligament of Treitz is taken down, and the jejunum is then mobilized to the patient’s right side. This allows for clear visualization of the pancreatic head/uncinate/SMV relationship. At this point, proximal and distal control of the PV, SMV, and SV should be obtained using vessel loops or umbilical tape. The dissection then proceeds laterally along the SMA border (posterior to the pancreatic head). This is often facilitated by use of a bipolar sealing device due to a rich lymphovascular network. Once the lateral border of the SMA is clearly exposed, dissection along its longitudinal axis is performed utilizing the jejunum for traction. Following this dissection, larger vessels such as the inferior pancreaticoduodenal artery can be more readily identified and ligated to fully mobilize the pancreatic head. After the head is completely separated from the SMA, the neck is divided. This leaves the specimen attached solely by the PV and SMV, which greatly facilitates venous resection and reconstruction when necessary.ConclusionThe ‘artery first’ approach has been shown to be safe and feasible in pancreatic resections. This technique should be considered whenever tumor is thought to involve the SMV and/or PVs as a means to facilitate safe venous resection and reconstruction while preserving sound oncologic principles.