ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

Survival and prognostic factors after transplantation, resection and ablation in a national cohort of early hepatocellular carcinoma.

BACKGROUND: In patients with early hepatocellular cancer (HCC) and preserved liver function, the choice between transplantation, resection and ablation and which factors to consider is not obvious and guidelines differ. In this national cohort study, we aimed to compare posttreatment survival in patients fulfilling predefined criteria, and to analyse preoperative risk factors that could influence decision. METHODS: We used data from HCC-patients registered with primary transplantation, resection or ablation 2008-2016 in the SweLiv-registry. In Child A-subgroups, 18-75 years, we compared survival after transplantation or resection, with different tumour criteria; either corresponding to our transplantation criteria (N = 257) or stricter with single tumours ≤50 mm (N = 159). A subgroup with single tumours ≤30 mm, compared all three treatments (N = 193). RESULTS: We included 1022 HCC-patients; transplantation n = 223, resection n = 438, ablation n = 361. In the transplant criteria subgroup, differences in five-year survival, adjusted for age and gender, were not significant, with 71.2% (CI 62.3-81.3) after transplantation (n = 109) and 63.5% (CI 54.9-73.5) after resection (n = 148). Good liver function (Child 5 vs. 6, Albumin ≥36), increased the risk after transplantation, but decreased the risk after resection and ablation. CONCLUSION: Even within Child A, detailed liver function assessment is important before treatment decision, and for stratifying survival comparisons.

Outcomes of Simultaneous Resections and Classical Strategy for Synchronous Colorectal Liver Metastases in Sweden: A Nationwide Study with Special Reference to Major Liver Resections.

BACKGROUND: About 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and surgical resection offers a chance for cure. The aim of the present study was to compare outcomes for patients that underwent simultaneous resection to those that underwent a staged procedure with the bowel-first (classical) strategy by using information from two national registries in Sweden. METHODS: In this prospectively registered cohort study, we analyzed clinical, pathological, and survival outcomes for patients operated in the period 2008-2015 and compared the two strategies. RESULTS: In total, 537 patients constituted the study cohort, where 160 were treated with the simultaneous strategy and 377 with the classical strategy. Patients managed with the simultaneous strategy had less often rectal primary tumors (22% vs. 31%, p = 0.046) and underwent to a lesser extent a major liver resection (16% vs. 41%, p < 0.001), but had a shorter total length of stay (11 vs. 15 days, p < 0.001) and more complications (52% vs. 36%, p < 0.001). No significant 5-year overall survival (p = 0.110) difference was detected. Twenty-five patients had a major liver resection in the simultaneous strategy group and 155 in the classical strategy group without difference in 5-year overall survival (p = 0.198). CONCLUSION: Simultaneous resection of the colorectal primary cancer and liver metastases can possibly have more complications, with no difference in overall survival compared to the classical strategy.

Incidental metastases and lymphoma of the gallbladder - an analysis of ten rare cases identified from a large national database.

Background: The aim was to identify and characterize rare malignancies of the gallbladder, incidentally found at cholecystectomy, and describe the diagnostic work-up, treatment and outcome. Methods: Data from cholecystectomies during 2007-2014 registered in the Swedish Register for Gallstone Surgery (GallRiks) were analyzed for incidental cancer. For completion of the pathology report, data were linked with the Swedish Registry for Cancer in the liver and biliary tract (SweLiv) and/or the Swedish Cancer Registry. Results: From 36,355 patients that underwent cholecystectomy on a benign indication 215 cases of incidental gallbladder cancer (IGBC) were identified. In total seven patients with metastases to the gallbladder from different primary tumors (breast cancer, malignant melanoma, gastric cancer, renal cell carcinoma, upper gastrointestinal cancer, colon cancer and pancreatic cancer) and three patients with lymphoma involvement of the gallbladder were found. Most patients were female with no difference between the groups (8/10 versus 171/215). The median age for the metastasis and lymphoma (MOL) group was equal to the IGBC group, 70 (64-72) years versus 70 (63-78) years. All patients in the MOL group underwent preoperative imaging with ultrasound or computed tomography, on which no metastases were identified. In only two patients a tumor was seen by the surgeon during the perioperative examination of the gallbladder. The median survival was 5.8 months for MOL patients and 23 months for IGBC patients. Conclusion: Metastases and lymphoma of the gallbladder are rare. Traditional imaging methods prior to cholecystectomy may miss gallbladder malignancies. A liberal approach of histopathological analysis of the gallbladder should be applied.

ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis: Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial).

OBJECTIVE: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). BACKGROUND: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. METHODS: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. RESULTS: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. CONCLUSION: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

Targeting dendritic cells in pancreatic ductal adenocarcinoma.

Dendritic cells (DC) are an integral part of the tumor microenvironment. Pancreatic cancer is characterized by reduced number and function of DCs, which impacts antigen presentation and contributes to immune tolerance. Recent data suggest that exosomes can mediate communication between pancreatic cancer cells and DCs. Furthermore, levels of DCs may serve as prognostic factors. There is also growing evidence for the effectiveness of vaccination with DCs pulsed with tumor antigens to initiate adaptive cytolytic immune responses via T cells. Most experience with DC-based vaccination has been gathered for MUC1 and WT1 antigens, where clinical studies in advanced pancreatic cancer have provided encouraging results. In this review, we highlight the role of DC in the course, prognosis and treatment of pancreatic cancer.

The impact of post-hepatectomy liver failure on mortality: a population-based study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers. AIM: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy. METHOD: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5. RESULTS: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3. CONCLUSION: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.

Significance of poor performance status after resection of colorectal liver metastases.

BACKGROUND: Performance status (PS) is known as one of the strongest prognostic factors for survival in metastatic colorectal cancer patients. The aim of the present study was to analyze factors associated with poor PS assessed after resection for colorectal liver metastases and the impact on survival. METHODS: All patients undergoing curative resection for colorectal liver metastases between 2010 and 2015 in a single center were reviewed retrospectively. RESULTS: A total of 284 patients were included, out of whom 74 patients (26%) presented with a postoperative PS WHO > 2 precluding administration of adjuvant chemotherapy. These patients had a shorter recurrence-free survival (P = 0.002) and shorter overall survival (P < 0.001). Multivariable analysis showed that patients with PS > 2 after surgery had higher preoperative ASA score, had a higher frequency of major complications after surgery, and had more frequently synchronous liver and lung metastases. PS was found to be the strongest independent factor predicting survival (hazard ratio 0.45). When patients with postoperative PS > 2 developed recurrent disease (54 of 74), 43 (80%) received tumor specific treatment. CONCLUSIONS: Patients with postoperative PS > 2 who did not receive adjuvant chemotherapy had decreased recurrence-free and overall survival after liver resection for colorectal liver metastases. After recurrence, a large majority of these patients had had improvement in PS allowing for administration of tumor specific treatment.

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

BACKGROUND: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. METHODS: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. RESULTS: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. CONCLUSION: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.

Liver-first strategy for synchronous colorectal liver metastases - an intention-to-treat analysis.

BACKGROUND: The liver-first strategy signifies resection of liver metastases before the primary colorectal cancer. The aim of the present study was to compare failure to complete intended treatment and survival in liver-first and classical strategies. METHODS: All patients with colorectal cancer and synchronous liver metastases planned for sequential radical surgery in a single institution between 2011 and 2015 were included. RESULTS: A total of 109 patients were presented to a multidisciplinary team conference (MDT) with un-resected colorectal cancer and synchronous liver metastases. Seventy-five patients were planned as liver-first, whereas 34 were recommended the classical strategy. Twenty-six patients (35%) failed to complete treatment in the liver-first group compared to 10 patients in the classical group (P = 0.664). Reason for failure was most commonly disease progression. A total of 91 patients had the primary tumor resected before the liver metastases of which 67 before referral and 24 after allocation at MDT. Median survival after diagnosis in this group was 60 (48-73) months compared to 46 (31-60) months in the group operated with liver-first strategy (n = 49), (P = 0.310). DISCUSSION: Up to 35% of patients with colorectal cancer and synchronous liver metastases do not complete the intended treatment of liver and bowel resections, irrespective of treatment strategy.

Bile Duct Injuries Associated With 55,134 Cholecystectomies: Treatment and Outcome from a National Perspective.

BACKGROUND: Bile duct injury (BDI) is a rare complication associated with cholecystectomy, and recommendations for treatment are based on publications from referral centers with a selection of major injuries and failures after primary repair. The aim was to analyze the frequency, treatment, and outcome of BDIs in an unselected population-based cohort. METHODS: This was a retrospective cohort study including all BDIs registered in GallRiks (Swedish quality register for gallstone surgery and ERCP) during 2007-2011. Data for this study were based on a national follow-up survey where medical records were scrutinized and BDIs classified according to the Hannover classification. RESULTS: A total of 174 BDIs arising from 55,134 cholecystectomies (0.3%) identified at 60 hospitals were included with a median follow-up of 37 months (9-69). 155 BDIs (89%) were detected during cholecystectomy, and immediate repair was attempted in 140 (90%). A total of 27 patients (18%) were referred to a HPB referral center. Hannover Grade C1 (i.e., small lesion <5 mm) dominated (n = 102; 59%). The most common repair was "suture over T-tube" (n = 78; 45%) and reconstruction with hepaticojejunostomy was performed in 30 patients (17%). A total of 31 patients (18 %) were diagnosed with stricture, 19 of which were primarily repaired with "suture over T-tube." The median in-hospital-stay was 14 days (1-149). CONCLUSIONS: The majority of BDIs were detected during the cholecystectomy and repaired by the operating surgeon. Although this is against most current recommendations, short-term outcome was surprisingly good.

Disappearing liver metastases from colorectal cancer: impact of modern imaging modalities.

BACKGROUND: Chemotherapy is often used before a resection for colorectal liver metastases. After chemotherapy, metastases may disappear on cross-sectional imaging but residual metastatic disease may still exist. The aim of this retrospective study was to investigate the impact of new advancements in imaging technology such as magnetic resonance imaging (MRI) with liver-specific contrast (Gd-EOB-DTPA) and contrast-enhanced intra-operative ultrasound (CE-IOUS) on disappearing liver metastases (DLM). METHODS: Twenty-nine patients with one or more DLM undergoing surgical exploration were included. Pre-operative imaging consisted of contrast-enhanced multi-detector computed tomography (MDCT) and/or MRI with liver-specific contrast. At surgery, CE-IOUS was used when tumours known from pre-chemotherapy imaging were not found by inspection or intra-operative ultrasound. RESULTS: Patients presented 66 DLM. At surgical exploration, 42 DLM were identified and treated (64%). CE-IOUS detected one additional DLM not found by intra-operative ultrasound. For metastases ≤10 mm on histological analysis, imaging sensitivities for MRI and MDCT before surgery but after chemotherapy were 26/49 (53%) and 24/66 (36%), respectively. CONCLUSION: A majority of DLM are identified during surgery using intra-operative ultrasound, with only little additional value of CE-IOUS. The sensitivities of post-chemotherapy imaging modalities for small metastases are low in the setting of DLM. For surgical planning, an optimized pre-chemotherapy imaging is essential.

Nitinol versus steel partially covered self-expandable metal stent for malignant distal biliary obstruction: a randomized trial.

BACKGROUND AND STUDY AIMS: Covered nitinol alloy self-expandable metal stents (SEMSs) have been developed to overcome the shortcomings of steel SEMS in patients with malignant biliary obstruction. In a randomized, multicenter trial, we compared stent patency, patient survival, and adverse events in patients with partly covered stents made from steel or nitinol. PATIENTS AND METHODS: A total of 400 patients with unresectable distal malignant biliary obstruction were randomized at endoscopic retrograde cholangiopancreatography (ERCP) to insertion of a steel or nitinol partially covered SEMS, with 200 patients in each group. The primary outcome was confirmed stent failure during 300 days of follow-up.  RESULTS: At 300 days, the proportion of patients with patent stents was 77 % in the steel group, compared with 89 % in the nitinol group (P = 0.01). Confirmed stent failure occurred more often in the steel SEMS group compared with the nitinol SEMS group, in 30 versus 14 patients (P = 0.02). Stent migration occurred in 13 patients in the steel group and in 3 patients in the nitinol group (P = 0.01). Median patient survival (secondary outcome) was 137 days and 120 days in the steel SEMS and nitinol SEMS groups, respectively (P = 0.59). CONCLUSIONS: The nitinol SEMS showed longer patency time, and the nitinol group had fewer patients with stent failure, compared with the steel SEMS group. We could not detect any differences between the two groups regarding survival time, and regarding adverse event rate.Clinical trial registration : NCT 00980889.

Pancreaticoduodenectomy--the transition from a low- to a high-volume center.

OBJECTIVE: Previous studies have identified a significant volume-outcome relationship for hospitals performing pancreaticoduodenectomy (PD). However, scant information exists concerning the effects of increased caseload of PD within the same hospital. Here, we describe the effects of becoming a high-volume provider of PD. MATERIAL AND METHODS: The study group comprised 221 patients who underwent PD between 2000 and 2012. Hospital volume was allocated into three groups: low-volume (<10 PDs/year), years 2000-2004, n = 25; medium-volume (10-24 PDs/year), years 2005-2009, n = 86; and high-volume (≥25 PDs/year), years 2010-2012, n = 110. RESULTS: The annual number of PDs increased from 5 in 2000 to 39 in 2012. The median operative duration decreased over the volume categories (p < 0.001). Intraoperative blood loss dropped (p < 0.001). The need for intraoperative blood transfusion was reduced (p < 0.001). Increasing hospital volume was associated with fewer reoperations (p = 0.041) and shorter postoperative length of stay (p = 0.010). There was a tendency toward reduced mortality: 4.0% for the low-volume period, 2.3% for the medium-volume period, and 0% for the high-volume period (p = 0.066). CONCLUSIONS: The transition from a low- to a high-volume center resulted in optimized outcomes for PD and 0% operative mortality, favoring the continued centralization of this high-risk operation.