Eylon Lahat

Impact of time to surgery in the outcome of patients with liver resection for BCLC 0-A stage hepatocellular carcinoma

BACKGROUND & AIMS The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend resection for very early and early single hepatocellular carcinoma (HCC) patients. It is not known whether a delay in resection from the time of diagnosis (the time to surgery [TTS], i.e. the elapsed time from diagnosis to surgery) affects outcomes. We aim to evaluate the impact of TTS on recurrence and survival outcomes in patients with HCC. METHODS All patients resected for BCLC stage 0-A single HCC from 2006 to 2016 were studied to evaluate the impact of TTS on recurrence rate, recurrence-free survival (RFS), transplantability following recurrence, and intention-to-treat overall survival (ITT-OS). Propensity score matching (PSM) was further performed to ensure comparability. RESULTS The study population included 100 patients. Surgery was performed between 0.6 and 77 months after diagnosis (median TTS: three months; interquartile range: 1.8-4.6 months). There was no post-operative mortality. Compared to those with TTS <3 months, patients with TTS ≥3 months (70% of these patients had TTS 3-6 months) had a higher post-operative morbidity (36% vs. 16%, p = 0.02), a similar tumor recurrence rate (32% vs. 32%, p = 1.00), RFS (37% vs. 48%, p = 0.42), transplantability following tumor recurrence (63% vs. 50%, p = 0.48), and five-year ITT-OS (82% vs. 80%, p = 0.20). Similar results were observed after PSM. CONCLUSION Patients with BCLC stage 0-A single HCC can undergo surgery with TTS ≥3 months without impaired oncologic outcomes. An increase in the TTS within a safe range could allow time for proper evaluation before surgery, and ethical testing of new neoadjuvant treatments, aiming to reduce the high rate of tumor recurrence despite curative resection. LAY SUMMARY A delay of ≥3 months in time to resection after diagnosis in HCC patients meeting the European Association for the Study of Liver Disease/American Association for the Study of Liver Disease criteria for resection does not affect oncological and long-term outcomes compared to those with a delay to surgery of <3 months.

Laparoscopic Isolated Resection of Caudate Lobe (Segment 1): A Safe and Versatile Technique

Surgical resection for liver tumors of the caudate lobe is challenging owing to its location between the inferior vena cava and the portal bifurcation and its relationship to the hepatic veins. Some case reports of isolated laparoscopic caudate lobe resection have been reported in the literature with various techniques. The aim of this study was to propose a standardized technique of laparoscopic isolated caudate lobe resection.

Role of Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation.

Context: The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is challenging, especially if it is not treatable by surgery or embolization. Objectives: The present study aims to compare the survival rates of liver transplanted patients receiving sorafenib or best supportive care (BSC) for HCC recurrence not amenable to curative intent treatments. Design: This is a retrospective comparative study on a prospectively maintained database. Participants: Liver transplanted patients with untreatable HCC recurrence receiving BSC (n = 18) until 2007 or sorafenib (n = 15) thereafter were compared. Results: No group difference was observed for demographic characteristics at the time of transplantation and at the time of HCC recurrence. On the explant pathology of the native liver, 81.2% patients were classified within the Milan criteria, and 53.1% presented with microvascular invasion. Hepatocellular carcinoma recurrence was diagnosed 17.8 months (standard deviation: 14.5) after LT, with 17 (53.1%) patients presenting with early recurrence (≤12 months). The 1-year survival from untreatable progression of HCC recurrence was 23.9% for the BSC and 60% for the sorafenib group (P = .002). The type of treatment (sorafenib vs BSC) was the sole independent predictor of survival (hazard ratio: 2.98; 95% confidence interval: 1.09-8.1; P = .033). In the sorafenib group, 8 (53.3%) patients required dose reduction, and 2 (13.3%) patients discontinued the treatment due to intolerable side effects. Conclusion: Sorafenib improves survival and is superior to the BSC in cases of untreatable posttransplant hepatocellular carcinoma recurrence.

Salvage Liver Transplantation or Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma: An Intent‐to‐treat Analysis

The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention‐to‐treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5‐year intention‐to‐treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5‐year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5‐year disease‐free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P < 0.001). Similar results were observed after propensity score matching. In conclusion, although the 5‐year OS rates were similar in the salvage LT and second resection groups, the salvage LT strategy still achieves better DFS. Second resection for recurrent HCC might be considered to be the best alternative option to LT in the current organ shortage. Liver Transplantation 23 1553–1563 2017 AASLD.

Impact of intraoperative blood transfusion on short and long term outcomes after curative hepatectomy for intrahepatic cholangiocarcinoma: a propensity score matching analysis by the AFC-IHCC study group

BACKGROUND The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained. METHODS All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method. RESULTS Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491). CONCLUSIONS IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection.

Conservative and surgical management of pancreatic trauma in adult patients.

BACKGROUND The management of pancreatic trauma is complex. The aim of this study was to report our experience in the management of pancreatic trauma. METHODS All patients hospitalized between 2005 and 2013 for pancreatic trauma were included. Traumatic injuries of the pancreas were classified according to the American Association for Surgery of Trauma (AAST) in five grades. Mortality and morbidity were analyzed. RESULTS A total of 30 patients were analyzed (mean age: 38±17 years). Nineteen (63%) patients had a blunt trauma and 12 (40%) had pancreatic injury ≥ grade 3. Fifteen patients underwent exploratory laparotomy and the other 15 patients had nonoperative management (NOM). Four (13%) patients had a partial pancreatectomy [distal pancreatectomy (n=3) and pancreaticoduodenectomy (n=1)]. Overall, in hospital mortality was 20% (n=6). Postoperative mortality was 27% (n=4/15). Mortality of NOM group was 13% (n=2/15) in both cases death was due to severe head injury. Among the patients who underwent NOM, three patients had injury ≥ grade 3, one patient had a stent placement in the pancreatic duct and two patients underwent endoscopic drainage of a pancreatic pseudocyst. CONCLUSIONS Operative management of pancreatic trauma leads to a higher mortality. This must not be necessarily related to the pancreas injury alone but also to the associated injuries including liver, spleen and vascular trauma which may cause impaired outcome more than pancreas injury.

Hepatic venous outflow block caused by compressive fecaloma in a schizophrenic patient treated with clozapine.

In Clozapine users constipation is among the reported side effects including agranulocytosis and myocarditis with prevalence rates ranging from 14% to 60%. In extreme cases this may lead to bowel obstruction and paralytic ileus which, if not detected and treated early, may lead to mortality up to 30%. We report the first case of hepatic outflow block secondary to compression of the liver by a distended colon upstream an impacted fecaloma in a 47-year old schizophrenic man treated by clozapine. Emergency sub-total colectomy was performed for pan-colonic ischemia. Surgery relieved the liver outflow block and was followed by uneventful outcome. Patients receiving clozapine should undergo routine laxatives and monitoring in order to limit the risk of clozapine-related ileus and bowel ischemia.

Liver Transplantation for Neuroendocrine Tumors: What Have We Learned?

Neuroendocrine tumors are slow-growing tumors and associated with prolonged overall survival even in the presence of untreated liver metastases. The presence of liver metastases may be responsible for severe symptoms with impairment of quality of life. Liver resection has been proposed to achieve better symptom control and/or improve overall survival, but this concerns less than 20% of patients with liver metastases. In addition, the chance to be really cured after liver resection is around 40%, which prompts consideration of liver transplantation as the only potential curative treatment. Time has come to move beyond the traditional debate around the best candidates and prognostic factors for liver transplantation. This review gives the opportunity to discuss new insights: (1) outcome of liver transplantation for neuroendocrine liver metastases as compared with hepatocellular carcinoma, (2) outcome of salvage liver transplantation as a secondary procedure after surgical resection of neuroendocrine liver metastases, (3) outcome of palliative liver transplantation for neuroendocrine liver metastases, and (4) the chance to be cured after liver transplantation for neuroendocrine liver metastases.

Ligation versus no ligation of spontaneous portosystemic shunts during liver transplantation: Audit of a prospective series of 66 consecutive patients

The management of large spontaneous portosystemic shunt (SPSS) during liver transplantation (LT) is a matter of debate. The aim of this study is to compare the short‐term and longterm outcomes of SPSS ligation versus nonligation during LT, when both options are available. From 2011 to 2017, 66 patients with SPSS underwent LT: 56 without and 10 with portal vein thrombosis (PVT), all of whom underwent successful thrombectomy and could have portoportal reconstruction. The SPSS were either splenorenal (n = 40; 60.6%), left gastric (n = 16; 24.2%), or mesenterico‐iliac (n = 10; 15.1%). Following portoportal anastomosis, the SPSS was ligated in 36 (54.4%) patients and left in place in 30 (45.5%) patients, based on the effect of the SPSS clamping/unclamping test on portal vein flow during the anhepatic phase. Intraoperatively, satisfactory portal flow was obtained in both groups. Primary nonfunction (PNF) and primary dysfunction (PDF) rates did not differ significantly between the 2 groups. Nonligation of SPSS was significantly associated with a higher rate of postoperative encephalopathy (P < 0.001) and major postoperative morbidity (P = 0.02). PVT occurred in 0 and 3 patients in the ligated and nonligated shunt group, respectively (P = 0.08). A composite end point, which included the relevant complications in the setting of SPSS in LT (ie, PNF and PDF, PVT, and encephalopathy) was present in 16 (44.4%) and 22 (73.3%) patients of the ligated and nonligated shunt group, respectively (P = 0.02). Patient (P = 0.05) and graft (P = 0.02) survival rates were better in the ligated shunt group. In conclusion, the present study supports routine ligation of large SPSS during LT whenever feasible. Liver Transplantation 24 505–515 2018 AASLD.

Liver transplantation in elderly patients: a systematic review and first meta-analysis

BACKGROUND Elderly recipients are frequently discussed by the scientific community but objective indication for this parameter has been provided. The aim of this study was to synthesize the available evidence on liver transplantation for elderly patients to assess graft and patient survival. METHODS A literature search of the Medline, EMBASE, and Scopus databases was carried out from January 2000 to August 2018. Clinical studies comparing the outcomes of liver transplantation in adult younger (<65 years) and elderly (>65 years) populations were analyzed. The primary outcomes were patient mortality and graft loss rates. This review was registered (Number CRD42017058261) as required in the international prospective register for systematic review protocols (PROSPERO). RESULTS Twenty-two studies were included involving a total of 242,487 patients (elderly: 23,660 and young: 218,827) were included in this study. In the meta-analysis, the elderly group had patient mortality (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.97-1.63; P = 0.09; I2 = 48%) and graft (HR: 1.09; 95% CI: 0.81-1.47; P = 0.59; I2 = 12%) loss rates comparable to those in the young group. CONCLUSIONS Elderly patients have similar long-term survival and graft loss rates as young patients. Liver transplantation is an acceptable and safe curative option for elderly transplant candidates.