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Objective To comprehensively assess the level of achievement and demographics of national surgical society presidents. Background Data on the accomplishments needed to rise to positions of national surgical leadership is scarce and merit alone does not always yield such opportunities. Recognizing the shortcomings of sex and ethnic diversity within academic surgical leadership, the American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and the Society of Black Academic Surgeons (SBAS) partnered to address these challenges by performing a comprehensive assessment of their presidents over the last 16 years. Methods ACS, ASA, AWS, and SBAS presidents' CVs, at the time of their presidential term, were assessed for demographics and scholastic achievements. Regression analyses controlling for age were performed to determine relative differences across societies. Results A total of 62 of the 64 presidents' CVs were received and assessed (97% response rate). There was a large discrepancy in the average age in years of ACS (70) and ASA (66) presidents compared to the AWS (51) and SBAS (53) presidents. For the ACS and ASA cohort, 87% were male and 83% were White, collectively. After controlling for age (52), the AWS and SBAS presidents' scholastic achievements were comparable to the ACS (and ASA) cohort in 9 and 12 of the 15 accessed metrics, respectively. Conclusion The ACS and ASA presidents' CVs displayed unsurpassed scholastic achievement, and although not equivalent, both the AWS and the SBAS presidents had comparable attainment. These findings further substantiate that women and ethnic minority surgeons are deserving of additional national leadership consideration as organized medicine pursues a more diverse and reflective physician workforce.

OBJECTIVE The objective of this study was to determine the impact of opioid use disorder (OUD) on perioperative outcomes after major upper abdominal surgeries. SUMMARY OF BACKGROUND DATA OUD, defined as dependence/abuse, is a national health epidemic. Its impact on outcomes after major abdominal surgery has not been well characterized. METHODS Patients who underwent elective esophagectomy, total/partial gastrectomy, major hepatectomy, and pancreatectomy were identified using the National Inpatient Sample (2003-2015). Propensity score matching by baseline characteristics was performed for patients with and without OUD. Outcomes measured were in-hospital complications, mortality, length of stay (LOS), and discharge disposition. RESULTS Of 376,467 patients, 1096 (0.3%) had OUD. Patients with OUD were younger (mean 53 vs 61 years, P < 0.001) and more often male (55.1% vs 53.2%, P < 0.001), black (15.0% vs 7.6%, P < 0.001), Medicaid beneficiaries (22.0% vs 6.4%, P < 0.001), and in the lowest income quartile (32.6% vs 21.3%, P < 0.001). They also had a higher rate of alcohol (17.2% vs 2.8%, P < 0.001) and nonopioid drug (2.2% vs 0.2%, P = 0.023) dependence/abuse. After matching (N = 1077 OUD, N = 2164 no OUD), OUD was associated with a higher complication rate (52.9% vs 37.3%, P < 0.001), including increased pain [odds ratio (OR) 3.5, P < 0.001], delirium (OR 3.0, P = 0.004), and pulmonary complications (OR 2.0, P = 0.006). Additionally, OUD was associated with increased LOS (mean 12.4 vs 10.6 days, P = 0.015) and nonroutine discharge (OR 1.6, P < 0.001). In-hospital mortality did not differ (OR 2.4, P = 0.10). CONCLUSION Patients with OUD more frequently experienced complications and increased LOS. Close postoperative monitoring may mitigate adverse outcomes.

Objective Assess the safety of overlapping surgery before implementation of new recommendations and regulations. Background Overlapping surgery is a longstanding practice that has not been well studied. There remains a need to analyze data across institutions and specialties to draw well-informed conclusions regarding appropriate application of this practice. Methods Coarsened exact matching was used to assess the impact of overlap on outcomes amongst all surgical interventions (n = 61,524) over 1 year (2014) at 1 health system. Overlap was categorized as: any, beginning, or end overlap. Study subjects were matched 1:1 on 11 variables. Serious unanticipated events were studied including unplanned return to operating room, readmission, and mortality. Results In all, 8391 patients (13.6%) had any overlap and underwent coarsened exact matching. For beginning/end overlap, matched groups were created (total matched population N = 4534/3616 patients, respectively). Any overlap did not predict unanticipated return to surgery (9.8% any overlap vs 10.1% no overlap; P = 0.45). Further, any overlap did not predict an increase in reoperation, readmission, or emergency room (ER) visits at 30 or 90 days (30D reoperation 3.6% vs 3.7%; P = 0.83, 90D reoperation 3.8% vs 3.9%; P = 0.84) (30D readmission 9.9% vs 10.2%; P = 0.45, 90D readmissions 6.9% vs 7.0%; P = 0.90) (30D ER 5.4% vs 5.6%; P = 0.60, 90D ER 4.8% vs 4.7%; P = 0.71). In addition, any overlap was not associated with mortality over the surgical follow-up period (90D mortality 1.7% vs 2.1%; P = 0.06). Beginning/end overlap had results similar to any overlap. Conclusion Overlapping, nonconcurrent surgery is not associated with an increase in reoperation, readmission, ER visits, or unanticipated return to surgery.

Objective To characterize the results of surgery for gastrointestinal stromal tumor (GIST) in the pre and post-imatinib eras at a single institution and to identify current prognostic clinicopathologic factors. Background Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined. Methods We retrospectively analyzed 1000 patients who underwent surgery for GIST at our institution from 1982 to 2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM + MET), or metachronous recurrence/metastases (MET), and also imatinib era (before and after it became available). Cox proportional-hazard models and Kaplan-Meier methods were used to model and estimate overall survival (OS) and recurrence-free survival (RFS). Results OS was longer in the imatinib era compared with the pre-imatinib era in each presentation group, including in Miettinen high-risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10 cm remained independently prognostic of RFS [hazard ratio (HR) 3.85, 95% confidence interval (CI) 2.00-7.40, P Conclusions Patients treated in the imatinib era had prolonged OS across all presentations. In the imatinib era, among site, size, and mitotic rate, high-risk features were associated with treatment with the drug, but only size >10 cm correlated with outcome. Imatinib should still be prescribed for patients with high-risk features.

Objective We sought to quantify the financial impact of elective surgery cancellations in the United States (US) during COVID-19 and simulate hospitals' recovery times from a single period of surgery cessation. Background COVID-19 in the United States (US) resulted in cessation of elective surgery-a substantial driver of hospital revenue-and placed patients at risk and hospitals under financial stress. We sought to quantify the financial impact of elective surgery cancellations during the pandemic and simulate hospitals' recovery times. Methods Elective surgical cases were abstracted from the Nationwide Inpatient Sample (2016-2017). Time series were utilized to forecast March-May 2020 revenues and demand. Sensitivity analyses were conducted to calculate the time to clear backlog cases and match expected ongoing demand in the post-COVID period. Subset analyses were performed by hospital region and teaching status. Results National revenue loss due to major elective surgery cessation was estimated to be $22.3 billion (B). Recovery to market equilibrium was conserved across strata and influenced by pre- and post-COVID capacity utilization. Median recovery time was 12-22 months across all strata. Lower pre-COVID utilization was associated with fewer months to recovery. Conclusions Strategies to mitigate the predicted revenue loss of $22.3B due to major elective surgery cessation will vary with hospital-specific supply-demand equilibrium. If patient demand is slow to return, hospitals should focus on marketing of services; if hospital capacity is constrained, efficient capacity expansion may be beneficial. Finally, rural and urban non-teaching hospitals may face increased financial risk which may exacerbate care disparities.

MINI: Patients with colorectal liver metastases and available KRAS data treated with resection and with or without adjuvant hepatic artery infusion chemotherapy were retrospectively evaluated. Adjuvant hepatic artery infusion was independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant hepatic artery infusion may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM. OBJECTIVE To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery.Early reports suggested that patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts.Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined. Multivariate analysis was conducted on all patients undergoing GIST metastasectomy between 2001 and 2014 at 2 institutions.We performed 400 operations on 323 patients with metastatic GIST on TKIs. Radiographic response at time of surgery was classified as responsive disease (RD, n = 64, 16%), stable disease (SD, n = 100, 25%), unifocal progressive disease (UPD, n = 132, 33%), and multifocal progressive disease (MPD, n = 104, 26%). For patients on imatinib before surgery, radiographic response was predictive of PFS from time of surgery (RD 36 months, SD 30 months, UPD 11 months, MPD 6 months; P0.001) and from imatinib initiation (RD 71 months, SD 51 months, UPD 47 months, MPD 33 months; P0.001). Radiographic response was predictive of OS from time of surgery (RD not reached, SD 110 months, UPD 59 months, MPD 24 months; P0.001), and from imatinib initiation (RD not reached, SD 144 months, UPD 105 months, MPD 66 months; P = 0.005). Radiographic response was not predictive of PFS/OS for patients on sunitinib. Metastatic mitotic index ≥5/50 HPF, MPD, and R2 resection were prognostic of worse PFS/OS; primary mutation was not.Surgery in metastatic GIST patients in the absence of MPD on imatinib is associated with outcomes at least comparable with second-line sunitinib and may be considered in select patients.

In 2015, the American Gastroenterological Association recommended the discontinuation of radiographic surveillance after 5 years for patients with stable pancreatic cysts. The current study evaluated the yield of continued surveillance of pancreatic cysts up to and after 5 years of follow up.A prospectively maintained registry of patients evaluated for pancreatic cysts was queried (1995-2016). Patients who initially underwent radiographic surveillance were divided into those with5 years and ≥5 years of follow up. Analyses for the presence of cyst growth (5 mm increase in diameter), cross-over to resection, and development of carcinoma were performed.A total of 3024 patients were identified, with 2472 (82%) undergoing initial surveillance. The ≥5 year group (n = 596) experienced a greater frequency of cyst growth (44% vs. 20%; P0.0001), a lower rate of cross-over to resection (8% vs 11%; P = 0.02), and a similar frequency of progression to carcinoma (2% vs 3%; P = 0.07) compared with the5 year group (n = 1876). Within the ≥5 year group, 412 patients (69%) had demonstrated radiographic stability at the 5-year time point. This subgroup, when compared with the5 year group, experienced similar rates of cyst growth (19% vs. 20%; P= 0.95) and lower rates of cross-over to resection (5% vs 11%; P0.0001) and development of carcinoma (1% vs 3%; P= 0.008). The observed rate of developing cancer in the group that was stable at the 5-year time point was 31.3 per 100,000 per year, whereas the expected national age-adjusted incidence rate for this same group was 7.04 per 100,000 per year.Cyst size stability at the 5-year time point did not preclude future growth, cross-over to resection, or carcinoma development. Patients who were stable at 5 years had a nearly 3-fold higher risk of developing cancer compared with the general population and should continue long-term surveillance.

The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use.We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006].An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$).Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571).The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.

Objective To evaluate the efficacy of surgical treatment for patients with isolated breast cancer liver metastases (BCLM). Background Single-arm retrospective studies have shown promising results associated with surgery for isolated BCLM; however, this treatment remains controversial and its role is not well-defined. Methods A review of 2150 patients with BCLM who underwent treatment in a single institution was conducted, and 167 (8%) patients with isolated BCLM were identified. A case-control study was conducted to compare outcomes in patients with isolated BCLM who underwent surgery and/or ablation to patients who underwent conventional medical therapy. Results A total of 167 patients were included (surgery/ablation: 69; medical: 98), with a median follow-up for survivors of 73 months. Patients in the surgical cohort more frequently had estrogen receptor-positive tumors and received adjuvant chemotherapy and radiotherapy for their primary breast tumor. The hepatic tumor burden was less and the interval from breast cancer diagnosis to BCLM was significantly longer (53 vs 30 months) in the surgical cohort. Patients undergoing surgical treatment had a median recurrence-free interval of 28.5 months (95% confidence interval (CI): 19-38) with 10 patients (15%) recurrence free after 5 years. There was no significant difference in overall survival (OS) between the surgical and medical cohorts (median OS: 50 vs 45 months; 5-year OS: 38% vs 39%). Conclusions Hepatic resection and/or ablation was not associated with a survival advantage. However, significant recurrence-free intervals can be accomplished with surgical treatment. Surgical intervention might be considered in highly selected patients with the goal of providing time off of systemic chemotherapy.

OBJECTIVE: This study aims to validate a previously reported recurrence clinical risk score (CRS). SUMMARY OF BACKGROUND DATA: Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations. METHODS: An international, multicenter cohort of R0 resected HCC patients were categorized by MC status at presentation. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidences were estimated using competing risks methodology, and conditional recurrence probabilities were estimated using the Bayes theorem. RESULTS: From 1992 to 2015, 1023 patients were identified, of whom 613 (60%) recurred at a median follow-up of 50 months. CRS was well validated in that all 3 factors remained independent predictors of recurrence beyond MC (HR 1.5–2.1, all p

OBJECTIVE: This study aimed to compare the incidence of radiologically unrecognized (occult) hepatocellular carcinoma (HCC) lesions in explant hepatectomy specimens from orthotopic liver transplants (OLTs) performed for HCC with rates of HCC intrahepatic recurrence after resection. SUMMARY OF BACKGROUND DATA: Resection of HCC is associated with high rates of intrahepatic HCC recurrence. However, it is unclear whether these recurrences represent incomplete resection of unrecognized metastatic lesions from the primary tumor or subsequent de novo tumor formation due to inherent biological proclivity for HCC formation. METHODS: We collected patient, tumor, and pathology data on HCC patients treated surgically from 3696 OLTs in the Organ Procurement and Transplantation (OPTN) national database, 299 OLTs at a single transplant center, and 232 partial hepatectomies from a hepatobiliary cancer center. RESULTS: In the OPTN and high-volume transplant center cohorts, 37% and 42% of patients had occult HCC lesions on explant pathology, respectively. Among cancer center patients, the 2-year recurrence rate was 46%, and 74% of patients who recurred presented with liver only recurrence. CONCLUSION: Although the transplant and resection populations differ, occult multifocality is common in transplant explants and similar to the 46% early recurrence rate following partial hepatectomy. These data suggest that non-curative resection often results from occult intrahepatic multifocality present at the time of resection rather than a malignant predisposition of the remnant liver with de novo tumorigenesis.

Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset.IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another.Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set.We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively.For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined.We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma.Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies.Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA).This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

OBJECTIVE: To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). BACKGROUND: GIST is the most common sarcoma. Although surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT protooncogene or, less frequently, platelet-derived growth factor receptor alpha is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. METHODS: This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group, registered at ClinicalTrials.gov as NCT00025246. From September 2001 to September 2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg per day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). RESULTS: After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rates were 99%, 97%, and 83%, which compared favorably with a historical 5-year OS rate of 35%. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96%, 60%, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. CONCLUSIONS: Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared with that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246).

To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.A tissue microarray was constructed including 127 patients with resected PDA and either short-term (12 months) or long-term (30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes (eg, recurrence pattern and early cancer-specific mortality) were determined.Loss of SMAD4 expression in pancreatic adenocarcinoma was identified in 40 of 127 patients (32%). SMAD4 loss occurred in 27% of patients who experienced isolated local recurrence, 33% of patients with a distant recurrence, 33% of patients who experienced local and distant site recurrences, and 25% of patients who were without evidence of recurrence (Fisher exact, P = 0.9). In a multivariate analysis, the presence of regional lymph node metastases was the only factor associated with the development of distant metastases (odds ratio = 4.7, P = 0.02). SMAD4 was neither associated with recurrence pattern (odds ratio = 0.9, P = 0.9) nor associated with early death (odds ratio = 0.5, P = 0.15).Primary tumor SMAD4 expression status was not a predictor of recurrence pattern in a large cohort of patients with resected PDA.

The aim of the study was to evaluate outcomes after resection of colorectal liver metastases (CRLM) and concurrent extrahepatic disease (EHD), and to define prognostic factors.There is increasing evidence to support resection of liver metastases and concurrent EHD in selected patients. Long-term survival data are lacking, and prognostic factors are not well defined.Retrospective review of 219 patients was undertaken between January 1992 and December 2012, who underwent hepatectomy for CRLM and resection of synchronous EHD. Survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. A scoring system for prognostication was developed.The median, 3, 5, and 10-year overall survival were 34.4 months, 49%, 28%, and 10%, respectively. Disease recurred in 185 patients (90.2%) at a median of 8 months. There were 8 actual 10-year survivors. The site of EHD affected survival, with portal, retroperitoneal nodes and multiple sites associated with the worst prognoses. The size of the largest CRLM, the number of CRLM, unfavorable site of EHD, and progression of CRLM on neoadjuvant therapy were associated with overall survival on univariate and multivariate analyses. Three variables, assigned 1 point each, were used to create an EHD risk score: largest CRLM greater than 3 cm, greater than 5 CRLM, and unfavorable site of EHD. The resulting score was prognostic of overall and recurrence-free survival.Long-term survival is possible after resection of liver metastases and concurrent EHD, but true cure is rare. A proposed scoring system may identify patients most likely to benefit from surgery.

The aim of this study is to examine, by a prospective randomized controlled trial, the influence of liberal (LIB) vs restricted (RES) perioperative fluid administration on morbidity following pancreatectomy.Randomized controlled trials in patients undergoing major intra-abdominal surgery have challenged the historical use of LIB fluid administration, suggesting that a more restricted regimen may be associated with fewer postoperative complications.Patients scheduled to undergo pancreatic resection were consented for randomization to a LIB (n = 164) or RES (n = 166) perioperative fluid regimen. Sample size was designed with 80% power to decrease Grade 3 complications from 35% to 21%.Between July 2009 and July 2015, we randomized 330 patients undergoing pancreaticoduodenectomy (PD, n = 218), central (n = 16), or distal pancreatectomy (DP, n = 96). Patients were equally distributed for all demographic and intraoperative characteristics. Intraoperatively, LIB patients received crystalloid 12 mL/kg/h and RES patients 6 mL/kg/h. Cumulative crystalloid given (median, range, mL) days 0 to 3 was LIB: 12,252 (6600 to 21,365), RES 7808 (2700 to 16,274) P0.0001. Sixty-day mortality was 2 of 330 (0.6%). Median operative time for PD was 227 minutes (105 to 462) and DP 150 (44 to 323). Grade 3 complications occurred in 20% of LIB and 27% of RES patients (P = 0.6). Median length of stay was 7 and 5 days for PD and DP, respectively, in both arms.In a high volume institution, major perioperative complications from pancreatic resection were not significantly influenced by fluid regimens that differed approximately 1.6-fold.

The potential benefit of adjuvant hepatic arterial infusional floxuridine (HAI-FUDR) in addition to modern systemic chemotherapy using oxaliplatin or irinotecan remains unknown for patients with resected liver-confined colorectal metastases (CRLM). The principle aim of this study was to compare outcomes in patients receiving modern systemic chemotherapy with or without HAI-FUDR.Between 2000 and 2005, 125 patients underwent resection of CRLM followed by adjuvant HAI-FUDR plus dexamethasone (Dex) and concurrent systemic chemotherapy including oxaliplatin or irinotecan. These patients were compared retrospectively to 125 consecutive patients who received modern systemic chemotherapy alone after liver resection.The median follow-up for all patients was 43 months. There were no differences in clinical risk score, disease-free interval, size of largest CRLM, number of CRLM, or prehepatectomy CEA level between the 2 groups. Adjuvant HAI-FUDR was associated with an improved overall and liver recurrence-free survival (liver RFS) and disease-specific survival (DSS). For the adjuvant HAI-FUDR group, the 5-year liver RFS, overall RFS, and DSS were 75%, 48%, and 79%, respectively, compared to 55%, 25%, and 55% for the systemic alone group (P0.01). On multivariate analysis, adjuvant treatment including HAI-FUDR was independently associated with improved liver RFS (HR = 0.34), overall RFS (HR = 0.65), and DSS (HR = 0.39), P0.01.Adjuvant HAI-FUDR combined with modern systemic chemotherapy is independently associated with improved survival compared to adjuvant systemic chemotherapy alone. A randomized clinical trial between these 2 regimens is justified.

Pancreaticoduodenectomy (PD) can be associated with significant blood loss and transfusion requirements, with potential adverse short- and long-term consequences. The aim of this study was to determine whether acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces perioperative allogeneic transfusions in patients undergoing PD.One hundred thirty patients undergoing PD were randomized to ANH or standard management (STDM). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL; crystalloid and colloid were used for volume replacement. Strict transfusion triggers were applied during and after operation. Perioperative complications were prospectively assessed and graded for severity.From July 2005 to May 2009, 209 patients were registered, 79 excluded, 65 were randomized to ANH, and 65 to STD. The groups were well matched for demographic, operative, and histopathologic variables. Patients undergoing ANH received over 2 L more fluid intraoperatively (6250 mL, range 2000-11850) compared with patients undergoing STD (3900 mL, range 2000-9000) (P0.001). Transfusion rates were similar (ANH = 16.9%, 30 units vs STD = 18.5%, 33 units; P = 0.82), as was overall perioperative morbidity (ANH = 49.2% vs STD = 47%, P = 0.86). There was, however, a trend toward more grade-3 complications in patients undergoing ANH (32% vs 23.1% STD, P = 0.17), and complications related to the pancreatic anastomosis (leak/fistula/abscess) were significantly higher in the ANH group (21.5% vs 7.7%, P = 0.045). The intraoperative fluid volume was higher for all patients with pancreatic anastomotic complications (n = 19), regardless of randomization arm (ANH 6000 mL, range 2800-11350 mL vs STD 5000 mL, range 2000-11850 mL, P0.042).In this randomized trial of patients undergoing PD, ANH did not reduce allogeneic transfusions and resulted in more pancreatic anastomotic complications, likely related to greater intraoperative fluid administration. The benefits of ANH do not necessarily extend to all procedures, and restrictive intravenous fluid management during PD may help improve postoperative outcome.

To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA).The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer.A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987-2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis.Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P0.0001, hazard ratio = 2.1 [95% CI: 1.4-3.2]). The median total lymph node count was 6 (range: 0-42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0-16] vs. 12 [range: 1-42], P0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node countor=11 (52.6 +/- 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively).Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

To determine if the degree of blood loss during resection of hepatocellular carcinoma (HCC) is predictive of recurrence and long-term survival.Several studies have addressed the impact of blood transfusion on survival and recurrence after liver resection for HCC. However, the independent effect of intraoperative estimated blood loss (EBL) on oncologic outcome is unclear.From our prospective database, we identified 192 patients who had a partial hepatectomy for HCC from 1985 to 2002. Clinicopathologic predictors of EBL were identified using logistic regression. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were assessed using the Kaplan-Meier and Cox regression methods.The median patient age was 64 (range, 19-86) and 66% were men. All patients had histologically proven HCC. The median follow-up time was 34 months (range, 1-297). Factors associated with increased EBL on multivariate analysis were male gender, vascular invasion, extent of hepatectomy, and operative time (P0.01). EBL and vascular invasion were independent predictors of OS and DSS. Only EBL was significantly associated with RFS on multivariate analysis (P = 0.02). Additionally, we found a significant inverse correlation between increasing levels of EBL and length of DSS (P = 0.01).The magnitude of EBL during HCC resection is related to biologic characteristics of the tumor as well as the extent of surgery. Increased intraoperative blood loss during HCC resection is an independent prognostic factor for tumor recurrence and death.

Purpose Resection is the most effective treatment for metastatic colorectal cancer (MCRC) to the liver. However, postoperative morbidity is common and its impact on long-term oncological outcome is unclear. The objective of this study was to evaluate the impact of postoperative morbidity on the long-term outcome after liver resection for MCRC. Methods Medical records of patients who underwent liver resection for MCRC with curative intent between 1991 and 2002 were reviewed. Patients who died of postoperative complications were excluded; operative and perioperative data, including morbidity and clinicopathological variables, were analyzed. Patients were stratified by disease extent and risk of recurrence using a clinical risk scoring system. Results A total of 1067 patients were included in the study and the median follow-up period was 41 months. The overall morbidity rate was 42%; the 5-year disease-specific survival (DSS) and overall disease-free survival (DFS) rates of patients who had complications were 41% and 25%, respectively, compared with 48% and 33%, respectively, for patients who did not have complications (P = 0.0059 for DSS, P = 0.0053 for DFS). On multivariate analysis, morbidity was not an independent predictor of either DSS or DFS; however, in a subgroup of patients with low clinical risk scores, morbidity was associated with a significant reduction in both DSS and DFS. Conclusions Postoperative morbidity adversely affects long-term outcome after hepatic resection for MCRC in patients at lower risk for recurrence. Efforts aimed at reducing perioperative morbidity will not only reduce usage of resources but will likely further enhance the therapeutic benefit of resection for such patients.

Objective: The aim of this study was to determine the results of liver resection for patients with bilateral hepatic metastases from colorectal cancer. We aimed to assess the evolution of the technical approach over time and correlations with morbidity, mortality, and oncologic outcome. Summary Background Data: Although hepatic resection for isolated colorectal metastases to the liver is thought to be beneficial when feasible, resection of bilateral liver metastases carries unique technical issues and is often associated with more aggressive tumor biology. Little has been written specifically about the results achieved in this subset of patients. Methods: Data from a prospectively maintained database of patients undergoing hepatic resection at a single institution over an 11-year time period were reviewed. Results: Resection of bilateral liver metastases from colorectal cancer was accomplished in 443 cases (440 patients) with a 29% incidence of major complications and a 5.4% 90-day mortality. Kaplan-Meier estimated 5-year disease-specific survival was 30% and 5-year recurrence-free survival was 18%. Operative technique changed over time toward a parenchymal-sparing approach as evidenced by the greater use of multiple simultaneous liver resections, wedge resections, and ablations. Similarly, there was a decrease in the use of major hepatectomies. This correlated with decreased mortality without change in disease-specific survival or liver recurrence. Conclusions: Resection of bilateral colorectal liver metastases can be accomplished with acceptable morbidity, mortality, and oncologic results. Increased use of a parenchymal-sparing approach is associated with decreased mortality without compromise in cancer-related outcome.

Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. GIST most often originates in the stomach or small intestine but can also arise in extraintestinal sites, such as the mesentery and omentum. Patients with primary localized GIST who undergo complete resection of their disease often develop tumor recurrence, and the 5-year survival can be as low as 54%.1 Historically, the outcome of patients with advanced GIST (unresectable primary disease or metastatic disease) has been poor, with a median survival of approximately 1.5 years.1 The response rate to conventional cytotoxic chemotherapy was only 5%.2 In 1998, Hirota et al identified activating mutations in the KIT proto-oncogene in GIST.3 Subsequent reports have found KIT mutations in up to 85% of GIST while another 3% to 5% have a PDGFRα mutation.4–6 Imatinib mesylate (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) inhibits the KIT and PDGFRα tyrosine kinases and was first applied to GIST in 2000.7 Imatinib achieves a partial response or stable disease in nearly 80% of patients, and remarkably the 2-year survival in advanced GIST is now 75% to 80%.7,8 More recently, sunitinib (Sutent, Pfizer, New York, NY), which inhibits VEGFR in addition to KIT and PDGFRα, has proven efficacious in patients who are intolerant or refractory to imatinib.9 While the majority of patients initially benefit from tyrosine kinase inhibitors, it is now clear that resistance commonly develops. Indeed, the median time to progression on imatinib mesylate is 2 years.8 Previously, we and others have defined the major mechanisms of acquired imatinib resistance in GIST.10–13 To improve the results of targeted therapy in metastatic GIST, we have used a multimodality approach that includes surgery. Here, we report the clinical outcome of 40 patients with metastatic GIST who were treated with tyrosine kinase inhibitors and then underwent surgery.

To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association.There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression.We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and intermediate-grade dysplasia: n = 48) and high-risk (high-grade dysplasia and invasive carcinoma: n = 30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation.Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs were identified in 2%, 33%, and 89% of the lesions when stratified by grade of dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and invasive carcinoma, respectively (P 0.001). Higher grades of dysplasia were also found to have positive correlation with 29 of the measured proteins, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia.In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease.

Resection remains the most effective therapy for selected patients with primary and secondary hepatic malignancy. In general, metastatic disease to extrahepatic sites is associated with poor survival and has been a contraindication to hepatic resection. In particular, regional metastases to perihepatic lymph nodes are a significant negative prognostic factor for both primary1–3 and secondary hepatic malignancies.4–8 On the other hand, selected patients with limited regional nodal disease may benefit from resection.7 Furthermore, as improvements in systemic chemotherapy continue to evolve, particularly for metastatic colorectal cancer, regional lymph node status may not necessarily be used to determine resectability but rather to select patients for optimal postresection chemotherapeutic therapies.9 The reported rate of perihepatic lymph node positivity in patients undergoing hepatic resection varies by histology,10 ranging from 10.6%7 to 28%5 in patients with hepatic colorectal metastases, 27%3 to 45%11 for intrahepatic cholangiocarcinoma and approximately 5% for hepatocellular carcinoma.12 Many of these studies include patients with obvious nodal involvement. Clearly, some patients have microscopic disease that is beyond detection by conventional radiographic imaging or even direct palpation. As a result, some authors have advocated routine lymph node sampling or lymphadenectomy for all patients undergoing hepatic resection.10,13 Although it has been suggested that occult metastasis to perihepatic lymph nodes is relatively common in patients with malignant liver disease, the incidence of truly occult disease is difficult to determine. Furthermore, there is currently no consensus regarding the optimal method of preoperative or intraoperative assessment of perihepatic lymph nodes in patients undergoing resection for hepatic malignancy. The present study investigates and compares the relative value of preoperative imaging (CT and PET) and intraoperative assessment of perihepatic lymph nodes, and particularly aims to determine the incidence of metastatic involvement that is clinically and radiographically undetectable.

This review describes the pathologic and epidemiologic features of gastrointestinal stromal tumor (GIST) as well as the contemporary management of this tumor. The integration of surgery and treatment with targeted molecular agents in the treatment of GIST is highlighted.GIST is the most common mesenchymal tumor of the gastrointestinal tract. Its cellular origin from the interstitial cell of Cajal and distinctness from smooth muscles tumors were only recently appreciated. The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST.We conducted a review of the English literature on GIST. The pathology, epidemiology, diagnosis, and treatment of this tumor are summarized with particular emphasis on recent developments in the field.GIST is a rare tumor that usually arises from the stomach or small intestine. It is characterized by immunohistochemical staining for KIT. Treatment of primary localized tumors is surgical. The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. The treatment of unresectable, recurrent, or metastatic GIST is primarily imatinib treatment. The integration of surgery or ablative modalities is often employed, particularly when all disease is amenable to gross resection or destruction, or when GIST becomes resistant to imatinib. Newer tyrosine kinase inhibitors, such as sunitinib are the subject of ongoing investigation.The treatment paradigm for GIST has required the integration of surgery and molecular therapy and this will likely serve as a paradigm for the treatment of other solid tumors as targeted agents are developed.

Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer in the world.1,2 In the United States, there will be 20,200 new cases of HCC this year, which is a 75% increase over the past decade and reflects the increased prevalence of chronic hepatitis infection.3 Three million people have chronic hepatitis C, and 1.2 million have chronic hepatitis B in the United States. These patients are estimated to develop HCC at a rate of 5% per year for chronic hepatitis C and 0.5% per year for hepatitis B.4,5 It is predicted that the number of deaths from HCC will rise dramatically over the next 10-15 years in this country.2,6,7 Partial hepatectomy has been the standard therapy for patients with HCC and good hepatic reserve when complete tumor resection is feasible. Five-year survival rates after resection have ranged from approximately 30 to 40%.8-14 Unfortunately, the majority of patients subsequently develop recurrent cancer in the liver remnant after resection.12,15 Adjuvant therapy has not been proven to be effective.16,17 In an attempt to achieve better results, surgeons have used liver transplantation for patients with HCC. The initial experience, in which transplantation was used liberally for patients with all stages of HCC, was discouraging, with 5-year survival rates ranging from 20-36%.18-22 It was noted, however, that patients with incidentally discovered HCC in the explanted liver and those with small tumors had similar survival comparable with patients undergoing liver transplantation for benign disease.23 Soon thereafter, the eligibility criteria for transplantation in patients with HCC were restricted. Mazzaferro et al24 published one of the first series to propose the currently accepted criteria for transplantation: a solitary tumor ≤ 5 cm, 2 or 3 tumors ≤ 3 cm in size, and the absence of vascular invasion. Four-year survival was reported at 75%, and 4 year recurrence free survival was 83%. Several other studies have confirmed these findings.20-23,25-28 Some authors have found the results to be so convincing that they are using liver transplantation as a first line treatment of patients with HCC and cirrhosis, regardless of the degree of liver dysfunction.29 However, the seemingly better results with transplantation versus partial hepatectomy may simply reflect the more stringent selection of patients with earlier stage HCC. In an attempt to determine whether partial hepatectomy or transplantation is a better treatment of early HCC, we examined the outcome of patients with early HCC treated with partial hepatectomy who would have been candidates for transplantation.

To determine the value of repeat liver resection for recurrent colorectal metastases to the liver.Liver resection represents the best and a potentially curative treatment for metastatic colorectal cancer to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver.This study reports the combined experience of repeat liver resection for recurrent liver metastases at an American and a European surgical oncology center. Patients were identified from prospective databases and records were retrospectively reviewed. A total of 126 patients (American n = 96, 1986-2001; European n = 30, 1985-1999) underwent repeat liver resection. Patient characteristics were similar in the two institutions. Median follow-up from first liver resection was 88 and 105 months, respectively.Operations performed included 90 minor resections and 36 resections of a lobe or more. The 1-, 3-, and 5-year survival rates were 86%, 51%, and 34%. There were 19 actual 5-year survivors to date. By multivariate regression analysis (proportional hazard model), more than one lesion and tumor size larger than 5 cm were independent prognostic indicators of reduced survival. The interval between the first and second liver resection was not predictive of outcome.Repeat liver resection for colorectal liver metastases is safe. Patients with a low tumor load are the best candidates for a repeat resection. In well-selected patients, further resection of the liver can provide prolonged survival after recurrence of colorectal liver metastases.

Cholangiocarcinoma is a rare disease, accounting for less than 2% of all human malignancies. 1 Although the entire biliary tree is potentially at risk, tumors involving the biliary confluence or the right or left hepatic ducts (hilar cholangiocarcinoma) are most common and account for 40% to 60% of all cases. 2–6 Meaningful clinical experience in managing hilar cholangiocarcinomas has been limited to a few referral centers because of the infrequency with which they are encountered. Although resection has long been recognized as the most effective therapy for hilar cholangiocarcinoma, 7 the importance of partial hepatectomy and the willingness of surgeons to use it routinely are relatively recent developments. 2,8–10 Many clinical series extend over a prolonged period, often greater than 20 years. 4,5,9,11,12 As a result, these reports lack a uniform approach to diagnosis, assessment of disease extent, and resection, and the results are therefore difficult to interpret. Further, most studies originate from surgical departments and tend to focus on surgical findings and results and often do not provide a full accounting of all patients seen. Long-term survival in patients with hilar cholangiocarcinoma depends critically on complete tumor resection. 2,10 In the absence of widespread disease, the likelihood of achieving a complete resection requires examination of all factors related to local tumor extent, which increasingly has become possible with noninvasive imaging studies. 13,14 Tumor location and extent within the biliary tree, as provided by the Bismuth-Corlette classification system, 15,16 is only one component. Additional factors that must be addressed relate to radial tumor growth and its impact on adjacent structures, specifically portal venous involvement and consequent hepatic lobar atrophy. Both the modified Bismuth-Corlette and the American Joint Committee on Cancer 17 staging systems fail to account for all of these local, tumor-related factors, which frequently influence therapy. We have shown previously that a preoperative staging system that accounts fully for local tumor-related factors accurately predicts resectability and correlates with survival. 2 The present study represents an analysis of all patients with hilar cholangiocarcinoma seen and treated at a single institution during a 9-year period. The organizational structure of the hepatobiliary program at Memorial Sloan-Kettering Cancer Center (MSKCC) allows a multidisciplinary review of all patients, regardless of disease stage. Thus, a full accounting of all patients, including those with unresectable tumors, is possible. The relatively short time interval ensures homogeneity with respect to disease assessment and surgical approach. This study also proposes a preoperative staging system, based on imaging data and modified from a previous report, 2 that stratifies patients into treatment groups with predictable resectability rates and survival.

This study evaluates the significance of tumor involvement of the liver in early T-stage tumors and lymph node (LN) metastases on outcome after R0 resection of gallbladder cancer (GBCA).A prospectively maintained database, supplemented with review of the medical record, was used to identify patients who underwent a complete (R0) resection for GBCA. All patients underwent definitive surgical treatment at the initial operation (1 stage) or after initial noncurative cholecystectomy (incidental tumors, 2 stage), including partial hepatectomy and portal LN dissection, with or without bile duct and/or adjacent organ resection. Clinicopathological variables, including TNM stage, histologic tumor involvement of liver (residual or direct extension in the GB fossa or discontiguous disease), and the total number of regional LNs assessed were analyzed for their association with outcome.One hundred twenty-two patients were identified and analyzed. The median follow up period was 23 months. Liver and nodal involvement by GBCA were observed in 61 (50%) and 41(34%) patients, respectively. Among patients with T2 tumors (n = 53), 48 (91%) were incidental. Liver involvement was present in 26%, and this factor was associated with decreased recurrence-free (RFS) and disease-specific survival (DSS) compared with patients with T2 tumors without liver involvement (median RFS, 12 months vs. not reached, P = 0.004, median DSS 25 months versus not reached, P = 0.003); T1b tumors (n = 10) were not associated with liver involvement. The median total lymph node count (TLNC) was 3 (range 0-20). For the entire cohort, survival of patients classified as N0 based on TLNC6 was significantly worse than that of N0 patients based on TLNC ≥ 6 (median RFS, 22 months versus not reached, P0.001, median DSS 41 months versus not reached, P0.001). Liver involvement and TLNC remained significant prognostic factors in a multivariate model that included TNM stage.Resection and histologic evaluation of at least 6 lymph nodes improves risk-stratification after resection of GBCA. Incidental T2 tumors are often associated with residual liver disease and should be reclassified to reflect the adverse outcome. The data suggests a need for standardized minimum requirements for adequate surgical treatment and pathological examination.

Objective: The purpose of this study was to characterize the clinicopathological features of invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas (IPMN) by histological subtype of the invasive component and to compare the outcomes of these patients to a cohort of matched patients with conventional ductal pancreatic adenocarcinoma. Background: Two distinct histological subtypes of invasive carcinomas arising in IPMNs have been described, colloid carcinoma and tubular carcinoma. Previous reports have suggested prognostic differences between these 2 subtypes but a matched comparison of colloid carcinoma, tubular carcinoma, and conventional pancreatic adenocarcinoma has not been reported. Methods: The clinicopathological variables of 59 patients resected for an invasive component of IPMN were analyzed with detailed pathologic review of histopathologic subtype (colloid carcinoma and tubular carcinoma). Using a postresection pancreatic adenocarcinoma nomogram, patients with either tubular or colloid carcinoma were matched on a 1:1 basis with patients resected for conventional ductal pancreatic adenocarcinoma. Clinicopathological factors and overall outcome was analyzed between the matched groups. Results: Fifty-nine patients underwent resection for IPMN with an associated invasive carcinoma (IPMN-INV). The estimated 3- and 5-year survival rates were 76% and 68%, respectively. Tubular carcinoma was present in 35 patients (59%) and 24 patients (41%) had colloid carcinoma. Tubular carcinoma subtype [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.2–11.6] and the presence of positive regional lymph nodes (HR 3.2 95% CI 1.2–8.2) were clinicopathological factors predictive of decreased survival by multivariate analysis. The 5-year estimated survival rates for tubular carcinoma and colloid carcinoma were 55% and 87%, respectively (P = 0.01). When compared with patients with conventional ductal pancreatic ductal adenocarcinoma resected during the same time period matched by a prognostic nomogram, patients with colloid carcinoma had a significantly longer survival outcome compared with patients with conventional adenocarcinoma (P = 0.0001). By contrast, survival after resection between patients with the tubular subtype (3-year estimated survival, 61%) and the matched group with conventional adenocarcinoma (3-year estimated survival, 21%) (P = 0.87) was not statistically different. Conclusions: In this study, the colloid carcinoma histological subtype of invasive IPMN had a more statistically favorable survival outcome than the tubular subtype. Patients with invasive tubular IPMN had no statistically significant difference in survival as matched patients with conventional ductal pancreatic carcinoma.

Background Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection. Methods One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay. Results From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025). Conclusion For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.

Despite data suggesting a rising worldwide incidence, intrahepatic cholangiocarcinoma (IHC) remains an uncommon disease. This study analyzes changes in IHC frequency, demographics, and treatment outcome in a consecutive and single institutional cohort.Consecutive patients with confirmed IHC seen and treated over a 16-year period were included. The trend in IHC frequency over the study period was compared with that of hilar cholangiocarcinoma patients (HCCA) seen during the same time. Demographics and patient disposition, histopathologic, treatment, recurrence, and survival data were analyzed; changes in these variables over time were assessed.From December 1990 through July 2006, 594 patients were evaluated (IHC = 270, HCCA = 324). Over the study period, the average annual increase in new IHC patients was 14.2% (P0.001). Relative to HCCA, the proportional increase in IHC was nearly 3-fold, and new IHC patients have outnumbered those with HCCA by 2:1 over the last 3 years. Conditions associated with IHC were rarely seen, with only 7 patients having a history of sclerosing cholangitis and/or inflammatory bowel disease and none with hepatolithiasis or biliary parasitic disease; however, heavy tobacco use (27%) and diabetes mellitus (16.4%) were particularly prevalent. The majority of patients were not candidates for resection, most commonly because of advanced hepatic disease. After resection (n = 82), median disease-specific survival was 36 months; recurrence was observed in 62.2% of patients at a median follow-up of 26 months, with the liver remnant involved most frequently (62.7%). Multiple hepatic tumors (P0.001), regional nodal involvement (P = 0.012), and large tumor size (P = 0.016) independently predicted poor recurrence-free survival. Most patients (n = 115, 73.7%) with unresectable disease were treated with chemotherapy, either systemic alone (n = 75) or combined with regional hepatic arterial floxuridine (FUDR) (n = 28). Compared with the first 10 years of the study (1990-2000), the last 6 years saw an overall improvement in disease-specific survival for all patients (22 vs. 12 months, P = 0.002), which was particularly notable for patients with unresectable disease (15 vs. 6 months, P = 0.003).At Memorial Sloan-Kettering Cancer Center, IHC incidence has increased dramatically in the last 16 years. Resection offers the best opportunity for long-term survival but is possible in the minority, and patients with large, node-positive or multifocal IHC seem to derive little benefit. Establishing and maintaining control of the intrahepatic disease remains the biggest problem for all IHC patients. The recent increase in survival seems largely because of improved nonoperative therapy for unresectable disease.

OBJECTIVES The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. PURPOSE Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. METHODS From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). RESULTS After a median wait of 30 +/- 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% +/- 3% compared with 26% +/- 3% for those without chemotherapy (P = NS). The number of patients with

Purpose: To develop a tool for predicting survival after liver resection for patients with stage IV colorectal cancer. By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure. Patients and Methods: All patients admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between January 1986 and December 1999 were included. A nomogram was developed as a graphical representation of a Cox proportional hazards regression model. The nomogram was verified for discrimination and calibration, both employing bootstrapping to obtain relatively unbiased estimates. Results: Using nodal status of the primary tumor, disease-free interval, size of the largest metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater than chance. The nomogram also had very good calibration. Conclusion: This nomogram is a predictive tool, upon external validation, that can routinely be used to counsel patients in making treatment decisions. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.

Hepatic resection is the only treatment modality associated with long-term survival in patients with colorectal liver metastasis. Five-year survival rates ranging from 25% to 58% have been reported with hepatic resection.1–3 With improved surgical techniques and chemotherapy, more patients are subjected to resection, including patients previously considered unresectable. Several clinicopathologic factors have been analyzed and are now considered to be independent prognostic factors associated with survival.4–13 The role of resection margin status as a prognostic factor to predict survival after hepatic resection for colorectal metastasis is controversial. In addition, the optimal margin width, if any, is unclear. Early documentation by some reports of a potential benefit associated with a 1-cm margin led to the general acceptance of this margin width to guide hepatic resections.14 Since that time, several studies addressing the issue of margin width have yielded conflicting results. Some authors have shown that a margin width >1 cm is associated with improved survival when compared with subcentimeter resections.4,15–19 In contrast, other reports have documented that the margin width does not have any effect on survival as long as it is negative,2,20,21 whereas some studies have noted that although a >1 cm margin is desirable, survival is not influenced by the width of the subcentimeter margin (0–9 mm).3,22 Firm conclusions from these studies are limited by small numbers of patients and limited statistical power. The only reports with a large number of patients were multi-institutional studies,2,7,11 in which institutional differences in the method of liver transection and pathologic analysis of the margin may confound the results. From these conflicting studies, the prognostic significance of margin status and the optimal margin width remain unclear. This is all the more important, since an increasing number of complex resections are performed in which the extent of hepatic involvement frequently mandates close resection margins. The aim of this study was to determine the impact of margin width on long-term survival after hepatic resection for colorectal metastasis in a large, consecutive series of patients from a single institution. Second, the study hopes to determine the influence of margin width on survival in the context of well-established clinicopathologic prognostic factors.

Objective: To define perioperative and long-term outcome and prognostic factors in patients undergoing hepatectomy for liver metastases arising from noncolorectal and nonneuroendocrine (NCNN) carcinoma. Summary Background Data: Hepatic resection is a well-established therapy for patients with liver metastases from colorectal or neuroendocrine carcinoma. However, for patients with liver metastases from other carcinomas, the value of resection is incompletely defined and still debated. Methods: Between April 1981 and April 2002, 141 patients underwent hepatic resection for liver metastases from NCNN carcinoma. Patient demographics, tumor characteristics, treatment, and postoperative outcome were analyzed. Results: Thirty-day postoperative mortality was 0% and 46 of 141 (33%) patients developed postoperative complications. The median follow up was 26 months (interquartile range [IQR]) 10–49 months); the median follow up for survivors was 35 months (IQR 11–68 months). There have been 24 actual 5-year survivors so far. The actuarial 3-year relapse-free survival rate was 30% (95% confidence interval [CI], 21–39%) with a median of 17 months. The actuarial 3-year cancer-specific survival rate was 57% (95% CI, 48–67%) with a median of 42 months. Primary tumor type and length of disease-free interval from the primary tumor were significant independent prognostic factors for relapse-free and cancer-specific survival. Margin status was significant for cancer-specific survival and showed a strong trend for relapse-free survival. Conclusions: Hepatic resection for metastases from NCNN carcinoma is safe and can offer long-term survival in selected patients. Hepatic resection should be considered if all gross disease can be removed, especially in patients with metastases from reproductive tract tumors or a disease-free interval greater than 2 years.

To evaluate the outcome of patients with liver metastases from sarcoma who underwent hepatic resection at a single institution and were followed up prospectively.The value of hepatic resection for metastatic sarcoma is unknown.There were 331 patients with liver metastases from sarcoma who were admitted to Memorial Hospital from 1982 to 2000, and 56 of them underwent resection of all gross hepatic disease. Patient, tumor, and treatment variables were analyzed to assess outcome.Of the 56 patients who underwent complete resection, 34 (61%) had gastrointestinal stromal tumors or gastrointestinal leiomyosarcomas. Half of the patients required an hepatic lobectomy or extended lobectomy. There were no perioperative deaths in the completely resected group, although 3 of the 75 patients who underwent exploration (4%) died. The postoperative 1-, 3-, and 5-year actuarial survival rates were 88%, 50%, and 30%, respectively, with a median of 39 months. In contrast, the 5-year survival rate of patients who did not undergo complete resection was 4%. On multivariate analysis, a time interval from the primary tumor to the development of liver metastasis greater than 2 years was a significant predictor of survival after hepatectomy.Complete resection of liver metastases from sarcoma in selected patients is associated with prolonged survival. Hepatectomy should be considered when complete gross resection is possible, especially when the time to the development of liver metastasis exceeds 2 years.

OBJECTIVE: The authors investigated whether adenoviral gene transfer to the thymus could be accomplished in vivo and whether immunologic unresponsiveness to recombinant adenovirus could be induced by intrathymic inoculation. SUMMARY BACKGROUND DATA: A major barrier to the clinical application of adenovirus-mediated gene therapy for diseases requiring long-lasting gene expression is the immunogenicity of adenoviral vectors, which limits the duration of its effects. In other experimental models, intrathymic inoculation of foreign proteins or cells has proven to be an effective means to induce immunologic tolerance. METHODS: The efficiency of gene transfer to the mouse thymus after direct inoculation of recombinant adenovirus was compared with that of several other vectors. Animals inoculated with adenovirus-infected pancreatic islets into the thymus were tested for unresponsiveness to the virus with a subsequent challenge of adenovirus administered into the liver by intravenous injection. RESULTS: Adenovirus accomplished highly efficient gene transfer to the thymus, unlike plasmid DNA, DNA-liposome complexes, retrovirus, and adeno-associated virus. Adenoviral transgene expression was transient in the thymus of immunocompetent mice but persistent in CD8+ T-cell-deficient and severe combined immunodeficiency (SCID) mice, implicating the role of cytotoxic T lymphocytes in viral clearance. Intrathymic transplantation of syngeneic pancreatic islet cells infected with adenovirus impaired the normal antiviral cytotoxic T-lymphocyte response and prolonged hepatic transgene expression after an intravenous challenge with adenovirus. CONCLUSIONS: Recombinant adenovirus accomplishes highly efficient gene transfer to the thymus in vivo. Intrathymic inoculation of adenovirus-infected islets can be used to induce immunologic unresponsiveness to the adenoviral vector and, potentially, to other proteins that it might be engineered to encode.