Chetana Lim

Complex Liver Resection Using Standard Total Vascular Exclusion, Venovenous Bypass, and In Situ Hypothermic Portal Perfusion: An Audit of 77 Consecutive Cases.

OBJECTIVE To identify independent predictors of 90-day mortality after liver resection for patients undergoing standard total vascular exclusion (TVE) with hypothermic portal perfusion and venovenous bypass. The secondary endpoint was to evaluate the long-term outcomes. BACKGROUND Tumors invading the vena cava and/or the hepatocaval confluence are indications for standard TVE. The inclusion of liver hypothermic perfusion permits safe TVE. There are a limited number of reports focusing on this complex technique and no relevant analysis of short-term and long-term results. METHODS Seventy-seven consecutive liver resections performed using standard TVE with hypothermic portal perfusion and venovenous bypass between 1998 and 2010 were analyzed. The independent predictors and rates of 90-day mortality, morbidity, and long-term survival were evaluated. RESULTS The 90-day mortality rate was 19.5% (15 cases). Three independent predictors of mortality were identified: age-adjusted Charlson Comorbidity Index 3 or more (P = 0.0231; odds ratio = 47.565; 95% confidence interval = 1.701-1330.414), tumor size 10 cm or more (P = 0.0442; odds ratio = 6.374; 95% confidence interval = 1.049-38.734), and the presence of 50/50 criteria (P = 0.0407; odds ratio = 6.217; 95% confidence interval = 1.080-35.782). The overall 5-year survival rate was 30.4%. CONCLUSIONS Liver resection using standard TVE with hypothermic portal perfusion and venovenous bypass is associated with a high mortality rate. The identification of preoperative predictors of mortality should improve the selection of patients for this aggressive surgery. Compared with nonsurgical management, the long-term results are acceptable and justify this aggressive surgery in selected patients.

Tumour progression and liver regeneration—insights from animal models

Surgery remains the only curative treatment for colorectal liver metastases. For patients with multiple bilobar spread, extended hepatectomy might be required to achieve complete margin-free resection. In such cases, portal vein occlusion has been developed to induce preoperative hypertrophy of the future remnant liver and increase the resectability rate. Evidence now suggests that liver regeneration after hepatectomy and portal vein occlusion has a protumorigenic role, either through an upregulation of growth factors and cytokines or by haemodynamic changes in the blood supply to the liver. Experimental studies have reported a stimulatory effect of liver regeneration on the tumoral volume of liver metastases and on the metastatic potential of cells engrafted in the liver; this effect seems to depend on the timing of hepatectomy and portal vein occlusion. However, the variability of animal tumour models that are used for research in experimental colorectal liver metastases might account for some of the inconsistent and conflicting results. This Review presents clinical and experimental data pertaining to whether liver regeneration causes proliferation of tumour cells. We also analyse the different animal models of colorectal liver metastases in use and discuss current controversies in the field.

Current use and perspective of indocyanine green clearance in liver diseases

Indocyanine green (ICG) is a water-soluble anionic compound that binds to plasma proteins after intravenous administration. It is selectively taken up at the first pass by hepatocytes and excreted unchanged into the bile. With the development of ICG elimination measurement by spectrophotometry, the ICG retention test has become a safe, rapid, reproducible, inexpensive and noninvasive tool for the assessment of liver function. Clinical evidence suggests that the ICG retention test can enable the establishment of tailored management strategies by providing prognostic information. In particular, this method has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and for the assessment of liver function in patients undergoing liver surgery. Since recent technology enables ICG-PDR to be measured noninvasively at the bedside, this parameter is an attractive addition to liver function and regional haemodynamic monitoring. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required.

Portal vein arterialization: a salvage procedure for a totally de-arterialized liver. The Paul Brousse Hospital experience

BACKGROUND Portal vein arterialization (PVA) has been used as a salvage inflow technique when hepatic artery (HA) reconstruction is deemed impossible in liver transplantation (LT) or hepatopancreatobiliary (HPB) surgery. Outcomes and the management of possible complications have not been well described. METHODS The present study analysed outcomes in 16 patients who underwent PVA during the period from February 2005 to January 2011 for HA thrombosis post-LT (n = 7) or after liver resection (n = 1), during curative resection for locally advanced HPB cancers (requiring HA interruption) (n = 7) and for HA resection without reconstruction (n = 1). In addition, a literature review was conducted. RESULTS Nine patients were women. The median age of the patients was 58 years (range: 30-72 years). Recovery of intrahepatic arterial signals and PVA shunt patency were documented using Doppler ultrasound until the last follow-up (or until shunt thrombosis in some cases). Of five postoperative deaths, two occurred as a result of haemorrhagic shock, one as a result of liver ischaemia and one as a result of sepsis. The fifth patient died at home of unknown cause. Three patients (19%) had major bleeding related to portal hypertension (PHT). Of these, two underwent re-exploration and one underwent successful shunt embolization to control the bleeding. Four patients (25%) had early shunt thrombosis, two of whom underwent a second PVA. After a median follow-up of 13 months (range: 1-60 months), 10 patients (63%) remained alive with normal liver function and one submitted to retransplantation. CONCLUSIONS Portal vein arterialization results in acceptable rates of survival in relation to spontaneous outcomes in patients with completely de-arterialized livers. The management of complications (especially PHT) after the procedure is challenging. Portal vein arterialization may represent a salvage option or a bridge to liver retransplantation and thus may make curative resection in locally advanced HPB cancers with vascular involvement feasible.

Liver resection using total vascular exclusion of the liver preserving the caval flow, in situ hypothermic portal perfusion and temporary porta-caval shunt: a new technique for central tumors

Standard total vascular exclusion (TVE) of the liver is indicated for resection of tumors involving or adjacent to the vena cava and/or the confluence of the hepatic veins. The duration of liver ischemia can be prolonged by combined portal hypothermic perfusion of the liver (in or ex situ). The use of a venovenous bypass (VVB) during standard TVE maintains stable hemodynamics as well as optimal renal and splanchnic venous drainage. When the hepatic veins can be controlled, TVE preserving the caval flow negates the need for VVB. However this technique remains limited in duration as it is performed under warm ischemia (so-called normothermia) of the liver. To prolong the ischemia time, we have designed a modification of TVE with preservation of the caval flow including the use of temporary porta-caval shunt (PCS) and hypothermic perfusion of the liver. We describe here the first two cases of this new technique. Two patients underwent left hepatectomy extended to segments 5 and 8 (also called extended left hepatectomy) for large centrally located tumors. TVE lasted seventy-two and seventy-nine minutes, respectively. The postoperative course was uneventful and both patients were discharged on day ten and day twenty-five respectively. Both are alive without recurrence at ten and seven months following surgery. Provided the roots of the hepatic veins can be controlled, this technique combines the advantages of standard TVE with in situ hypothermic perfusion and VVB and obviates the need and the subsequent risks of the latter.

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.

When the Patient Is Sicker Than His Liver.

To the Editor: We read with great interest the study by Petrowsky et al, recently published in Annals of Surgery, regarding the outcome of 169 patients (excluding acute liver failure), with a MELD (Model for End-Stage Liver Disease) score of 40 and higher, undergoing a first liver transplantation (LT). The authors define a futile transplantation by the 90-day or in-hospital mortality. They reported a mortality rate of 22%. A risk-prediction model, derived from the multivariate analysis of 14 donor and recipient related, identified 4 predictors of futile LT, namely MELD score, Charlson Comorbidity Index, cardiac risk, and pretransplant septic shock of 26 or more is correlated to a 90-day mortality rate of 50%. However, the following points must be addressed. The model was designed from a population of patients who underwent transplantation, and by the definition formerly listed. Besides this selection bias inherent to the study design, excluding patients who were listed but did not undergo transplantation, the model remains to be validated in and/or adapted to the population of patients not yet listed for transplantation, particularly those admitted for the first time in intensive care unit. In other terms, the first question ‘‘to list or not to list?’’ remains unanswered. We acknowledge that the variable studies are clinically sound. However, major physiological (neurocognitive, respiratory, nutritional issues) and laboratory values (lactates) or prognostic scores [Sequential Organ Failure Assessment (SOFA), CLIF-SOFA, Simplified Acute Physiology Score II (SAPS II)] are lacking, whereas their value is indisputable to guide clinical decision-making for liver organ allocation and transplantation in patients with decompensated cirrhosis receiving support in a critical care setting. Moreover, although the authors noted the usefulness of predictors of mortality that were based on changes in the scores over time, no dynamic factor has been associated in the analysis. Recently, the use of predictors of mortality that were based in the prognostics score over time, including organ failure patterns, has been showed to improve prognostic performance of model or score in such patients. Overall, when a patient is listed,

Evaluation of the current guidelines for resection of hepatocellular carcinoma using the Appraisal of Guidelines for Research and Evaluation II instrument

BACKGROUND & AIMS Numerous guidelines for the management of hepatocellular carcinoma (HCC) have been developed. The Appraisal of Guidelines for Research & Evaluation (AGREE II) is the only validated instrument to assess the methodological quality of guidelines. We aim to appraise the methodological quality of existing guidelines for the resection of HCC using the AGREE II instrument. METHODS Cochrane, Medline, Google Scholar and Embase were searched using both PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and free text. The assessment of the included clinical practice guidelines and consensuses were performed using the AGREE II instrument, version 2013. Guidelines with a score ⩾80% for the overall appraisal item were considered as applicable without modifications. RESULTS Literature searches identified 22 clinical practice guidelines. Five out of 22 guidelines passed the 70% mark on overall assessment, 11 out of 22 had shortcomings on indications, contraindications, side effects, key recommendations, technical aspects, transparency and health economics. Ten of 22 scored below the 50% mark showing that the guideline had low methodological and overall quality. Only 3/22 clinical practice guidelines were considered applicable without modifications. CONCLUSIONS The methodological quality of guidelines for the surgical management of HCC is generally poor. Future guideline development should be informed by the use of the AGREE II instrument. Guidelines based upon high quality evidence could improve stratification of patients and individualized treatment strategies. Lay summary: The methodology of clinical practice guidelines for resection for hepatocellular carcinoma (HCC) evaluated with the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument is generally poor. However, there are some clinical practice guidelines that are based upon higher quality evidence and can form the framework within which patients with HCC can be selected for surgical resection. Future guideline development should be informed by the use of the AGREE II instrument.

Intragastric migration of a mesentericoportal polytetrafluoroethylene jump graft after liver transplantation

A 67-year-old man was admitted for incoercible vomiting and septic shock. Resuscitation included antibiotics and antifungal agents for positive blood cultures (Streptococcus milleri, Bacteroides fragilis, and Candida glabrata). Eleven years before the current admission, the patient underwent cadaveric liver transplantation (LT) for alcoholic cirrhosis. Portomesenteric thrombosis was discovered intraoperatively. As vascular grafts from the donor were not available, a polytetrafluoroethylene (PTFE) graft was used to jump the native superior mesenteric vein to the graft portal vein. One year before the current admission, a routine computed tomography (CT) scan showed the graft was thrombosed but still in place. At the current admission, a CT scan showed gas in the graft and migration of its distal part into the gastric antrum (Fig. 1A), which was confirmed afterward by endoscopy (Fig. 1B). At laparotomy, the prosthesis, filled with pus (Enterobacter aerogenes and Candida glabrata), was removed through a posterior gastrotomy (Fig. 1C), and a gastrojejunal anastomosis was performed. The postoperative course was uneventful. Six months later, the patient was asymptomatic. Sepsis had not recurred, and liver function tests and CT scan were normal (Fig. 1D).

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.