Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Meta-analysis of associating liver partition with portal vein ligation and portal vein occlusion for two-stage hepatectomy.

BACKGROUND: Discussion is ongoing regarding whether associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) or portal vein occlusion is better in staged hepatectomy. The aim of this study was to compare available strategies using a two-stage approach in extended hepatectomy. METHODS: A literature search was performed in MEDLINE, Scopus, the Cochrane Library and Embase, and additional articles were identified by hand searching. Data from the international ALPPS registry were extracted. Clinical studies reporting volumetric changes, mortality, morbidity, feasibility of the second stage and tumour-free resection margins (R0) in two-stage hepatectomy were included. RESULTS: Ninety studies involving 4352 patients, including 320 from the ALPPS registry, met the inclusion criteria. Among these, nine studies (357 patients) reported on comparisons with other strategies. In the comparison of ALPPS versus portal vein embolization (PVE), ALPPS was associated with a greater increase in the future liver remnant (76 versus 37 per cent; P < 0·001) and more frequent completion of stage 2 (100 versus 77 per cent; P < 0·001). Compared with PVE, ALPPS had a trend towards higher morbidity (73 versus 59 per cent; P = 0·16) and mortality (14 versus 7 per cent; P = 0·19) after stage 2. In the non-comparative studies, complication rates were 39 per cent in the PVE group, 47 per cent in the portal vein ligation (PVL) group and 70 per cent in the ALPPS group. After stage 2, mortality rates were 5, 7 and 12 per cent respectively. CONCLUSION: ALPPS is associated with greater future liver remnant hypertrophy and a higher rate of completion of stage 2, but this may be at the price of greater morbidity and mortality.

Short Chemotherapy-Free Interval Improves Oncological Outcome in Patients Undergoing Two-Stage Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: In patients undergoing two-stage hepatectomy (TSH) for colorectal liver metastases (CRLM), chemotherapy is discontinued before portal vein occlusion and restarted after curative resection. Long chemotherapy-free intervals (CFI) may lead to tumor progression and poor oncological outcomes. OBJECTIVE: The aim of this study was to investigate the impact of the length of CFI on oncological outcome in patients undergoing TSH for CRLM. PATIENTS AND METHODS: Overall, 74 patients suffering from bilobar CRLM who underwent ALPPS (associating liver partition with portal vein ligation for staged hepatectomy; n = 43) or conventional TSH (n = 31) at two tertiary centers were investigated. The impact of CFI on long-term outcomes was analyzed by univariable and multivariable analysis. RESULTS: Preoperative chemotherapy was administered in 91 % (67/74) of patients, and chemotherapy was resumed postoperatively in 69 % (44/64) of patients who completed TSH. The use of postoperative chemotherapy was significantly associated with improved mean overall survival (36 ± 3 vs. 13 ± 3 months; p < 0.001). Overall, the median CFI from surgery to postoperative chemotherapy was 16 weeks (interquartile range 11-31) and was significantly shorter in the ALPPS group when compared with the conventional TSH group (10 vs. 21 weeks; p < 0.001). Multivariable analysis revealed a CFI ≤ 10 weeks as an independent factor associated with improved overall survival (p = 0.006) and disease-free survival (p = 0.010). CONCLUSION: A short CFI is associated with improved oncological outcome in patients undergoing TSH for CRLM. Decreased interstage intervals after ALPPS may facilitate the timely resumption of chemotherapy.

Epidural analgesia and perioperative kidney function after major liver resection.

BACKGROUND: Epidural analgesia (EDA) is a common analgesia regimen in liver resection, and is accompanied by sympathicolysis, peripheral vasodilatation and hypotension in the context of deliberate intraoperative low central venous pressure. This associated fall in mean arterial pressure may compromise renal blood pressure autoregulation and lead to acute kidney injury (AKI). This study investigated whether EDA is a risk factor for postoperative AKI after liver surgery. METHODS: The incidence of AKI was investigated retrospectively in patients who underwent liver resection with or without EDA between 2002 and 2012. Univariable and multivariable analyses were performed including recognized preoperative and intraoperative predictors of posthepatectomy renal failure. RESULTS: A series of 1153 patients was investigated. AKI occurred in 8·2 per cent of patients and was associated with increased morbidity (71 versus 47·3 per cent; P = 0·003) and mortality (21 versus 0·3 per cent; P < 0·001) rates. The incidence of AKI was significantly higher in the EDA group (10·1 versus 3·7 per cent; P = 0·003). Although there was no significant difference in the incidence of AKI between patients undergoing minor hepatectomy with or without EDA (5·2 versus 2·7 per cent; P = 0·421), a substantial difference in AKI rates occurred in patients undergoing major hepatectomy (13·8 versus 5·0 per cent; P = 0·025). In multivariable analysis, EDA remained an independent risk factor for AKI after hepatectomy (P = 0·040). CONCLUSION: EDA may be a risk factor for postoperative AKI after major hepatectomy.

Quantitative in vivo analysis of small bowel motility using MRI examinations in mice--proof of concept study.

Small bowel motility analyses using magnetic resonance imaging (MRI) could reduce current invasive techniques in animal studies and comply with the 'three Rs' rule for human animal experimentation. Thus we investigated the feasibility of in vivo small bowel motility analyses in mice using dynamic MRI acquisitions. All experimental procedures were approved by the institutional animal care committee. Six C57BL/6 mice underwent MRI without additional preparation after isoflurane anaesthetization in the prone position on a 4.7 T small animal imager equipped with a linear polarized hydrogen birdcage whole-body mouse coil. Motility was assessed using a true fast imaging in a steady precession sequence in the coronal orientation (acquisition time per slice 512 ms, in-plane resolution 234 × 234 µm, matrix size 128 × 128, slice thickness 1 mm) over 30 s corresponding to 60 acquisitions. Motility was manually assessed measuring the small bowel diameter change over time. The resulting motility curves were analysed for the following parameters: contraction frequency per minute (cpm), maximal contraction amplitude (maximum to minimum [mm]), luminal diameter (mm) and luminal occlusion rate. Small bowel motility quantification was found to be possible in all animals with a mean small bowel contraction frequency of 10.67 cpm (SD ± 3.84), a mean amplitude of the contractions of 1.33 mm (SD ± 0.43) and a mean luminal diameter of 1.37 mm (SD ± 0.42). The mean luminal occlusion rate was 1.044 (SD ± 0.45%/100). The mean duration needed for a single motility assessment was 185 s (SD ± 54.02). Thus our study demonstrated the feasibility of an easy and time-sparing functional assessment for in vivo small bowel motility analyses in mice. This could improve the development of small animal models of intestinal diseases and provide a method similar to clinical MR examinations that is in concordance with the 'three Rs' for humane animal experimentation.

Para-aortic lymph node sampling in pancreatic head adenocarcinoma.

BACKGROUND: The significance of positive para-aortic nodes in patients with resectable pancreatic carcinoma is unclear. This study sought to evaluate the accuracy of intraoperative detection and prognostic significance of these lymph nodes in patients with resected adenocarcinoma of the pancreatic head. METHODS: From 2000 to 2010, para-aortic node sampling was performed prospectively in all patients before pancreatoduodenectomy. Frozen sections were created and nodes categorized as positive or negative for metastases. Surgeons were blinded to the frozen-section results. This was followed by standard histopathological assessment of corresponding paraffin-embedded, haematoxylin and eosin-stained material. Nodes considered uninvolved by this analysis were examined immunohistochemically for micrometastases. RESULTS: A total of 111 consecutive patients were included, with a median follow-up of 20·8 (range 1·5-126) months. The 1-, 2- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 73·6, 54·0 and 24·7 per cent, and 51·8, 28·1 and 18·8 per cent respectively. Para-aortic node involvement was always associated with peripancreatic lymph node metastasis, and was detected by frozen-section analysis in 12 patients and by haematoxylin and eosin staining in 17. Sensitivity and specificity of frozen-section examination for detecting para-aortic lymph node metastases were 71 and 100 per cent respectively. Median OS for patients with and without para-aortic node involvement on frozen-section analysis was 9·7 versus 28·5 months respectively (P = 0·012), and 15·7 versus 27·2 months (P = 0·050) when assessed by haematoxylin and eosin staining. Median DFS for patients with and without para-aortic node involvement on frozen-section examination was 5·6 versus 12·9 months respectively (P = 0·041), and 8·4 versus 12·9 months (P = 0·038) for haematoxylin and eosin analysis. The presence of micrometastases in para-aortic nodes was not significantly associated with altered OS or DFS. CONCLUSION: Para-aortic node sampling with frozen-section examination detects distant lymphatic involvement reliably. It should be performed systematically. When metastases are found, they should be considered a contraindication to pancreatic resection.

Serotonin: a double-edged sword for the liver?

Since the discovery of the impact of serotonin in liver regeneration, this molecule has gained considerable attention in liver physio-pathology. Platelet-derived serotonin initiates liver regeneration after partial hepatectomy in various rodent models. Serotonin agonism stabilizes the hepatic microcirculation and prevents small-for-size liver graft failure. Similarly, serotonin receptor agonists improve the sinusoidal perfusion of aged liver and restore the deficient liver regeneration in old mice through a pathway dependent on vascular endothelial growth factor. Beside hepatocyte proliferation, cholangiocytes have been shown to be able to deploy serotonin as an autocrine/paracrine signal to regulate regeneration of the biliary tree. Increasing evidence indicates that serotonin is involved in many pathological conditions of the liver. For example, serotonin promotes tissue repair after ischemia/reperfusion injury. Reactive oxygen species generated by serotonin degradation contribute to steatohepatitis in rodent models. Serotonin aggravates viral hepatitis, again through vasoactive effects on the microcirculation, and plays a crucial role in the progression of hepatic fibrosis. Finally, serotonin may facilitate tumor growth of primary liver carcinoma like cholangiocarcinoma and hepatocellular carcinoma. These findings make serotonin both friend and foe for the liver. Whichever, these new data emphasize the potential of serotonin as a pharmacological target in liver disease.

Giant mesenteric cystic lymphangioma of mesocolic origin in an asymptomatic adult patient.

A 34-year-old patient was scheduled for valve replacement to treat a symptomatic mitral regurgitation. The preoperative work-up incidentally discovered an intra-abdominal cystic tumour extending from the epigastrium to the pelvic region on a computed tomography scan. The patient had no abdominal symptoms by the giant cyst from unkown origin. An open "en bloc" resection disclosed a large cyst in the mesocolon. Pathological examination, including immunohistochemistry, enabled the diagnosis of a mesenteric cystic lymphangioma. Long-term follow-up of 12 months shows no recurrence. Mesenteric cystic lymphangioma, which is extremely rare in adults, is a challenge to diagnose and needs complete resection to ensure dignity and to avoid recurrence.

Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre.

BACKGROUND: Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia-reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. METHODS: This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. RESULTS: Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. CONCLUSION: IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. REGISTRATION NUMBER: NCT00908245 (http://www.clinicaltrials.gov).

Is preoperative histological diagnosis necessary before referral to major surgery for cholangiocarcinoma?

Major surgical resection is often the only curative treatment for cholangiocarcinoma. When imaging techniques fail to establish the accurate diagnosis, biopsy of the lesion is unavoidable. However, biopsy is not necessarily required for topography of the cholangiocarcinoma (intrahepatic or extrahepatic). 1) In extrahepatic cholangiocarcinoma (ECC), clinical features and radiological imaging relate to biliary obstruction. Provided that between 8% and 43% of bile duct strictures are not ECC, the lesions mimicking ECC that should be ruled out are gallbladder cancer, Mirizzi syndrome, primary sclerosing cholangitis (PSC), autoimmune pancreatitis and portal biliopathy. Systematic biopsy is usually difficult and has poor sensitivity, but a good knowledge of these mimicking ECC diseases, along with precise analysis of clinical and imaging semiology, may lead to a correct diagnosis without the need for biopsy. 2) Intrahepatic cholangiocarcinoma (ICC) developing in normal liver appears as a hypovascular tumour with fibrotic component and capsular retraction that can be confused with fibrous metastases such as breast and colorectal cancers. The lack of the primary site, a relatively large tumour size and ancillary findings such as bile duct dilatation may provide a clue to the diagnosis. If not, we advocate local resection with lymph node dissection, since ICC is the most likely diagnosis and surgery is the only curative treatment. In the event of adenocarcinoma from unknown primary, surgery is an effective treatment even if prognosis is poor.

Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives.

Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases.

Right portal vein ligation is as efficient as portal vein embolization to induce hypertrophy of the left liver remnant.

BACKGROUND: Aim of this retrospective study was to compare induction of left liver hypertrophy after right portal vein ligation (PVL) and right portal vein embolization (PVE) before right hepatectomy for liver metastases. MATERIALS AND METHODS: Between 1998 and 2005, 18 patients underwent a PVE, whereas 17 patients underwent a PVL during a first stage laparotomy. RESULTS: There was no complication related to PVE or PVL. After a similar interval time (7 +/- 3 vs 8 +/- 3 weeks), the increase of the left liver volume was similar between the two groups (35 +/- 38 vs 38 +/- 26%). After PVE and PVL, right hepatectomy was performed in 12 and 14 patients, respectively. Technical difficulties during the right hepatectomy were similar according to duration of procedure (6.4 +/- 1 vs 6.7 +/- 1 h, p = 0.7) and transfusion rates (33 vs 28%, p = 0.7). Mortality was nil in both groups, and morbidity rates were respectively 58% for the PVE group and 36% for the PVL group (p = 0.6). CONCLUSION: Right PVL and PVE result in a comparable hypertrophy of the left liver. During the first laparotomy of a two-step liver resection, PVL can be efficiently and safely performed.

Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis.

The aim of this review was to assess the impact of transarterial chemoembolization (TACE) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). An electronic search on the Medline database (1990-2005) was used to identify relevant articles. The studies were reviewed and ranked according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. As a bridge to OLT, pretransplant TACE does not improve long-term survival (grade C). There is currently no convincing evidence that TACE allows to expand the current selection criteria for OLT, nor that TACE decreases dropout rates on the waiting list (grade C). However, TACE does not increase the risk for postoperative complications (grade C). There is insufficient evidence that TACE offers any benefit when used prior to OLT, neither for early nor for advanced HCC. Well-designed randomized controlled trials are needed to define the role of TACE in OLT patients.

Does laparoscopic colorectal resection for diverticular disease impair male urinary and sexual function?

BACKGROUND: Laparoscopic colorectal resection may induce bladder and sexual dysfunction secondary to injury to the autonomic nervous system. The aim of this study was to evaluate urinary and sexual function in male patients after laparoscopic colorectal resection for diverticular disease. METHODS: From January 1997 to March 2002, we performed a retrospective analysis of urinary and sexual function in 56 consecutive male patients who had undergone laparoscopic colorectal resection for diverticular disease. Preoperative and 6-month postoperative assessment was carried out using data collected via standardized postal questionnaires. RESULTS: Three patients were excluded (one had a prior prostatectomy, one had Peyronie's disease, and one was treated with neuroleptics). Fifty-three patients with a mean age of 54 A+/- 2 years were included in the study. There were no conversions. The morbidity rate was 9.4%. Mean follow-up was 27 A+/- 2 months. There was no significant difference in preoperative and postoperative urinary function. Fifty-one patients (96%) were sexually active preoperatively and were still sexually active postoperatively. Compared with the preoperative period, postoperative impairment of libido, erection, ejaculation, and orgasm were not significant. Every patient was able to achieve ejaculation after the intervention, and no retrograde ejaculations were reported. One patient was unable to have an erection after the intervention. CONCLUSION: Laparoscopic colorectal resection for diverticular disease does not significantly impair urinary and sexual function.

Intrahepatic cholangiocarcinoma and hepatolithiasis: an unusual association in Western countries.

Hepatolithiasis is uncommon in Western countries and the relationship with cholangiocarcinoma is unusual. We report the association of hepatolithiasis and a cholangiocarcinoma in a Caucasian patient with a 17-year history of recurrent pancreatitis associated with hepatolithiasis. We discuss work-up and surgical treatment, and stress the need to keep in mind the possible association between hepatolithiasis and cholangiocarcinoma even in Western countries.