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BACKGROUND: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors.METHODS: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit.RESULTS: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas.CONCLUSION: The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.

Clinical outcomes of octogenarians undergoing hepatectomy for colorectal liver metastases (CRLM) are poorly characterized. The current study evaluated operative morbidity, mortality and survival outcomes among a contemporary cohort of octogenarians.Patients undergoing their first hepatectomy for CRLM were identified from institutional databases and those ≥80 years old (y) were matched 1:1 to a group of patients80 y. Data pertaining to surgical morbidity/mortality and survival were compared using standard statistical methods.From 2002 to 2012, 1391 hepatectomies were performed for CRLM, 55 (4%) in patients ≥80 y. Major complications occurred twice as frequently among patients ≥80 y [10 (19%) ≥80 y versus 5 (9%)80 y, (p = 0.270)]. No matched patient80 y. died within 90 d of operation, whereas, 4 (7%) patients ≥80 y did, p = 0.125. Median follow-up was significantly longer for the80 y group [44 (1-146) versus. 23 (0-102) mths, p = 0.006]. Probability of disease recurrence was not different between groups (p = 0.123) nor was the cumulative incidence of death from disease (p = 0.371). However, patients ≥80 y had significantly higher incidence of non-cancer related death (p = 0.012).Hepatectomy for CRLM among well-selected octogenarians is reasonable with cancer related survival outcomes similar to those observed in younger patients. However, it is associated with clinically significant morbidity/mortality and continued efforts directed at optimizing perioperative care are necessary to improve early outcomes among octogenarians.

The aim of this study was to assess splenic volume and to correlate unidimensional measurements with reference volumetric changes in chemotherapy-treated patients with colorectal cancer (CRC) liver metastases.Forty consecutive patients were selected from the cohort of a previously reported study of chemotherapy-related morbidity following major hepatectomy for CRC liver metastases. Patients were treated for 6 months prior to resection, with imaging performed at baseline and after 6 months of chemotherapy. Three unidimensional spleen measurements were recorded-width, thickness, and height (W, T, and H). Reference splenic volume was measured at baseline and after chemotherapy. The best unidimensional splenic measurement was determined by regression analysis. The 95% CI for the predicted values and R (2) values was calculated for each regression. The percentage of volume increase at 6 months was calculated.W and H showed the highest correlation with splenic volume prior to and following chemotherapy (R (2) = 0.65-0.74, p 0.001), while T showed a low correlation (R (2) = 0.11 and 0.18, p 0.05). The mean reference splenic volume increased after 6 months of chemotherapy compared to baseline (326 vs. 278 mL). Splenic volume changes showed the highest correlation with changes in W (R (2) = 0.56, p 0.001), then H (R (2) = 0.40, p 0.001), but were not significantly correlated with changes in T (R (2) = 0.01, p = 0.055).Our results show the potential utility of measuring changes in splenic width to predict clinically significant changes in splenic volume in chemotherapy-treated patients with CRC liver metastases.

In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-induced hepatic injury is associated with increased splenic volume, thrombocytopenia, and decreased long-term survival. The current study investigates the relationship between change in splenic volume after preoperative chemotherapy and development of postoperative complications.The study group consisted of 80 patients who underwent resection of CRCLM; half received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the other half did not (n = 40). The study group was compared with two control groups: a normal group composed of patients undergoing cholecystectomy for benign disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC) patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study group, the nontumoral liver was graded for steatosis and sinusoidal injury; operative and outcomes characteristics were also analyzed.Before chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 ± 1.1 mL/kg, significantly higher than normal (2.5 ± 0.8 mL/kg; p0.001) and nonmetastatic CRC (2.6 ± 1.3 mL/kg; p0.05) patients, with higher splenic volume after 6 months of chemotherapy (4.2 ± 1.7 mL/kg; p0.01). After chemotherapy, splenic volume increase was associated with any perioperative complication (p0.01) and major complications (p0.05). Patients with ≥39% splenic volume increase (maximal chi-square test) were significantly more likely to have major complications (p0.01). Spleen volume changes were not correlated with change in platelet count (R(2) = 0.03; p = 0.301).In patients with CRCLM, the presence of liver metastases and chemotherapy are associated with higher splenic volume. Percent splenic volume increase after 6 months of chemotherapy can aid preoperative risk stratification, as it was an independent predictor of major postoperative complications.

To date, hepatic artery infusion (HAI) chemotherapy has primarily been investigated in the setting of colorectal cancer liver metastases (CRLM). Few studies have been conducted in North America regarding HAI chemotherapy for primary liver cancers (PLC) or noncolorectal liver metastases (non-CRLM). Despite decades of evaluation, controversy surrounding the use of HAI chemotherapy still exists. In this article the methods of HAI chemotherapy delivery, technical aspects of catheter and pump insertion, and specific complications of HAI chemotherapy are discussed. Outcomes of clinical trials and reviews of HAI chemotherapy in the setting of CRLM, PLC, and non-CRLM are evaluated.

Purpose To investigate whether perioperative hepatic arterial infusion pump chemotherapy (HAI) was associated with overall survival (OS) in patients who had a complete resection of colorectal liver metastases (CLM). Methods Patients who underwent a complete resection of CLM between 1992 and 2012 were included from a single-center prospectively maintained database. All patients who received HAI also received perioperative systemic chemotherapy. Propensity score analysis was used to match patients for seven known prognostic factors. Results A total of 2,368 consecutive patients underwent a complete resection of CLM, with a median follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67 months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For patients who received modern systemic chemotherapy (n = 1,442), the median OS was 67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59 to 0.76; P < .001). A pronounced difference in median OS was found for patients with node-negative colorectal cancer (129 months with HAI v 51 months without; P < .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53 months without; P < .001). Conclusion Patients who received HAI had a median OS of approximately 2 years longer than patients without HAI. The strong association was independent of the use of modern systemic chemotherapy and remained in propensity score analysis. Patients with node-negative primary tumors or a low clinical risk score seemed to benefit most from HAI.

Fistula Risk Score (FRS) is a previously developed tool to assess the risk of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD).Prospectively collected databases from 4 university affiliated and non-affiliated HPB centers in United States and Canada were used. The influence of individual baseline characteristics, FRS and FRS group on CR-POPF was assessed in univariate and multivariate analyses. FRS calculator performance was assessed using a C-statistic.444 patients were identified. Pathology, soft pancreas texture and pancreatic duct size were associated with CR-POPF rates (p 0.001 for each); EBL was not (p = 0.067). The negligible risk group consisted of 50 (11.3%) patients, low risk of 118 (26.6%), moderate 234 (52.7%) and high risk group of 42 (9.5%) patients. The overall rate of CR-POPF was 20%. Of the patients in the negligible risk group, 2% developed CR-POPF, 13.6% of the low risk, 23.1% moderate and 42.9% in the high risk group (p 0.001). Overall C-statistic was 0.719.FRS is robust and able to stratify the risk of developing CR-POPF following PD in diverse North American academic and non-academic institutions. The FRS should be used in research and to guide clinical management of patients post PD in these institutions.

Worldwide, colorectal cancer (CRC) is one of the most common malignancies. At presentation, metastatic spread is observed in approximately 20 % of patients with a further 50 % developing metastases during their disease course. In patients who develop metastases, 80 % have some form of liver involvement. The only treatment for patients with isolated colorectal cancer liver metastases (CRLM) associated with potential long-term survival and cure is surgery. Unfortunately, most patients (75–80 %) have disease that is not amenable to surgical intervention. However, recent advances in all areas of the management of CRLM have resulted in more numerous treatment options for this population of patients. Developments in diagnosis, medical therapy (chemotherapy, targeted therapy), nonsurgical locoregional therapy (ablation, embolization, hepatic artery infusion chemotherapy), and surgical therapy have expanded the treatment armamentarium for patients with CRLM and subsequently increased the complexity of management. Many newer therapies/treatment strategies have proven effective; however, there is debate regarding the ideal clinical implementation. In order to optimize clinical outcomes in patients with CRLM, awareness of current and emerging therapies and treatment strategies is essential.

Resection of colorectal liver metastases (CRLM) is associated with improved survival; however, the impact of time to resection on survival is unknown. The current multi-institutional study sought to evaluate the influence of time from diagnosis (Dx) to resection (Rx) on survival outcomes among patients with resectable, metachronous CRLM and to compare practice patterns across hospitals.Medical records of patients with ≤4 metachronous CRLM treated with surgery were reviewed and analyzed retrospectively. Time from Dx to Rx was analyzed as a continuous variable and also dichotomized into 2 groups (group 1: Dx to Rx3 months and group 2: Dx to Rx ≥3 months) for additional analysis. Survival time distributions after resection were estimated using the Kaplan-Meier method. Between-group univariate comparisons were based on the log-rank test and multivariable analysis was done using Cox proportional hazards model.From 2000 to 2010, six hundred and twenty-six patients were identified. Type of initial referral (p0.0001) and use of neoadjuvant (p = 0.04) and/or adjuvant (p0.0001) chemotherapy were significantly different among hospitals. Patients treated with neoadjuvant chemotherapy (n = 108) and those with unresectable disease at laparotomy (n = 5) were excluded from final evaluation. Median overall survival and recurrence-free survival were 74 months (range 63.8 to 84.2 months) and 29 months (range 23.9 to 34.1 months), respectively. For the entire cohort, longer time from Dx to Rx was independently associated with shorter overall survival (hazard ratio = 1.12; 95% CI, 1.06-1.18; p0.0001), but not recurrence-free survival. Median overall survival for group 1 was 76 months (range 62.0 to 89.2 months) vs 58 months (range 34.3 to 81.7 months) in group 2 (p = 0.10). Among patients with available data pertaining to adjuvant chemotherapy (N = 457; 318 treated and 139 untreated), overall survival (87 months [range 71.2 to 102.8 months] vs 48 months [range 25.3 to 70.7 months]; p0.0001), and recurrence-free survival (33 months [range 25.3 to 40.7 months] vs 22 months [range 14.5 to 29.5 months]; p = 0.05) were improved significantly.In select patients undergoing initial resection for CRLM, longer time from Dx to Rx is independently associated with worse overall survival. In addition, despite uniform disease characteristics, practice patterns related to definitely resectable CRLM vary significantly across hospitals.

The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements.A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater.A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors.Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.

The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation. Patients diagnosed with IPMN were identified from institutional databases, divided into two groups based on treatment type, pancreatectomy versus clinical observation, and subsequently evaluated. Standard demographic and clinicopathologic variables, fasting glucose, diabetic status, and pancreatic volume data, were obtained and compared between groups. One hundred thirty-four IPMN patients were identified; 103 (77 %) underwent pancreatectomy and 31 (23 %) were observed. Baseline DM rate was 18 % (24/134). This was not different between groups [17 % (17/103) resected vs. 23 % (7/31) observed, p = 0.51]. Median follow-up was 53 months and new/progressive DM occurred in 37 (28 %) patients with no difference between groups [29 (28 %) resected vs. 8 (26 %) observed, p = 0.74]. Among resected patients, degree of dysplasia was associated with increase risk of new/progressive DM [moderate dysplasia OR 5.76 (1.24–26.79) and severe dysplasia OR 9.43 (1.54–57.74), p = 0.04], while procedure type and remnant volume were not. The incidence and prevalence of DM among patients with IPMN was high and did not differ between resected and observed groups. Degree of dysplasia, not the amount of resected pancreas, was associated with increased risk of DM, suggesting that the presence or development of DM may be a marker of malignant progression. Confirmatory studies are required.

Purpose To evaluate the use of locoregional therapy in patients with hepatocellular carcinoma (HCC) with and without extrahepatic disease (EHD). Materials and Methods Patients who underwent locoregional therapy for HCC were identified from institutional databases. Clinicopathologic and treatment characteristics were compared between patients with and without EHD. Survival and progression were assessed using the Kaplan-Meier method, and multivariate analysis was completed. Results Of 224 patients, 39 (17%) had radiologic evidence of EHD. Patients without EHD were older than patients with EHD (68.8 y ± 10.1 vs 65.0 y ± 11.7, P = .04); underlying liver disease/function and tumor characteristics were not different. Type of locoregional therapy (hepatic artery embolization vs drug-eluting bead transarterial chemoembolization, P = .12; radiofrequency ablation + embolization, P = .07) was similar. Progression occurred in 75% (169/224) of patients. Progression-free survival (PFS) did not differ between the 2 groups (13 [10.3–15.7] mo EHD vs18 [14.6–21.4] mo no EHD, P=.13). Overall survival (OS) was 13 (4.1–21.9) months and 25 (20.4–29.6) months in the EHD and no EHD groups, respectively ( P = .02). On multivariate analysis, systemic therapy after locoregional treatment was the only variable independently associated with PFS (hazard ratio [HR] 0.70 [0.49–1.00], P = .04); EHD (HR 1.60 [1.02–2.50], P = .04) and tumor size (HR 1.77 [1.21–2.58], P = .003) were independently associated with worse OS. Conclusions Patients with HCC and limited EHD treated with locoregional therapy had worse OS than patients without EHD; PFS was not different. Use of systemic therapy after locoregional therapy was independently associated with improved PFS in this cohort. Further prospective studies of locoregional, systemic, and combination therapies are necessary to improve outcome in these high-risk patients.

Objective The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation.