Interventional treatment options for management of delayed arterial hemorrhage after major hepato-pancreatic-biliary surgery

Hilar cholangiocarcinoma is a biliary malignancy arising from the perihilar biliary tree,which is associated with poor oncological outcomes due to its aggressive biology,chemo-resistance and insidious onset[1].As stated by Di Martino et al.,the standard of care is radical resection,and during the last decades,there have been great efforts to improve survival of potentially resectable hilar cholangiocarcinoma,with surgery being the treatment associated with longer survival[2].However,radical resection still represents a challenging operation with high risk of intraoperative and postoperative complications.

Laparoscopic liver resection:Experience based guidelines

Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

Early changes of graft function,cytokines and superoxide dismutase serum levels after donor liver denervation and Kupffer cell depletion in a rat-to-rat liver transplantation model

BACKGROUND: Hepatic reperfusion injury may cause acute inflammatory damage, producing significant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. METHODS: Donor rats were divided into four groups: control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. RESULTS: HG pre-treatment significantly decreased ALT, TNF-alpha, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not significant at 4 postoperative hours. CONCLUSIONS: Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.

Does autologous blood transfusion during liver transplantation for hepatocellular carcinoma increase risk of recurrence?

AIM: To analyze outcomes in patients who underwent liver transplantation(LT) for hepatocellular carcinoma(HCC) and received autologous intraoperative blood salvage(IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher's exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death,and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test.RESULTS: Between 2002 and 2012,158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients,122(77.2%) were in the IBS group and 36(22.8%) in the non-IBS group. The overall survival(OS) and recurrence free survival(RFS) at 5 years were 59.7% and 83.3%,respectively. No differences in OS(P=0.51) or RFS(P=0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS,degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS,no differences were detected in OS or RFS(P=0.055 and P=0.512,respectively) according to the volume infused,even when outcomes at 90 d or longer were analyzed separately(P=0.518 for both outcomes).CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes.

Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy

Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions mis-diagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 small bilateral focal liver lesions, with magnetic resonance imaging consistent with colorectal liver metastases (CLM), and fluorodeoxyglucose (FDG)-positron emission tomography (PET) negative. The second patient had up to 5 small focal liver lesions, with computed tomography consistent with CLM, and FDG-PET negative. They had parenchyma sparing liver surgery, with uneventful postoperative course. At the histology the diagnosis was multiple FNHs. The risks of oxaliplatin- based chemotherapy regimens in development of liver injuries, such as FNH, should not be further denied.The value of the modern multidisciplinary management of patients with colorectal cancer relies also on the precise estimation of the risk/benefit for each patient.

Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma

Cholangiocarcinoma(CCC)is the most aggressive malignant tumor of the biliary tract.Perihilar CCC(pCCC)is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results.Besides its clinical presentation,a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis.Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure.During staging iter,magnetic resonance can obtain satisfactory cholangiographic images,while invasive techniques should be used if bile duct samples are needed.Consistently,to improve diagnostic potential,bile duct drainage is not necessary in jaundice,while it is indicated in refractory cholangitis or when liver hypertrophy is needed.Once resecability criteria are identified,the extent of liver resection is secondary to the longitudinal spread of CCC.While in the past type IV pCCC was not considered resectable,some authors reported good results after their treatment.Conversely,in selected unresectable cases,liver transplantation could be a valuable option.Adjuvant chemotherapy is the standard of care for resected patients,while neoadjuvant approach has growing evidences.If curative resection is not achieved,radiotherapy can be added to chemotherapy.This multistep curative iter must be carried on in specialized centers.Hence,the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.

Laparoscopic resection for hepatocellular carcinoma: eastern and western experiences

Hepatocellular carcinoma （HCC） is the most common primary liver cancer （1）. The incidence is rising in the last decades due to many factors, especially hepatitis C, alcoholic liver disease and non-alcoholic steatohepatitis. Moreover, the introduction of screening programs in patients with chronic liver disease has led to an increase in HCC diagnosis （1,2）. In the western world, 80% to 90% of HCC eases occur in patients with liver cirrhosis （3） while this proportion is lower in some regions in Asia and sub-Saharian Africa, where hepatitis B remains as an important etiologic factor for chronic liver disease （2,4）. In 1990, the annual world frequency of HCC was 437,000 cases/year （1）, and in 2012 the number reached 782,200 cases/year being responsible for 746,000 deaths （5）. Nowadays, HCC represents the 6th most frequent neoplastic disease in the world and the 3rd in mortality （5）.

Tailoring the area of hepatic resection using inflow and outflow modulation

The performance of hepatic surgery without a parenchyma-sparing strategy carries significant risks for patient survival because of the not negligible occurrence of postoperative liver failure.The key factor of modern hepatic surgery is the use of the intraoperative ultrasound(IOUS),not only to stage the disease,but more importantly to guide resection with the specific aim to maximize the sparing of the functional parenchyma.Whether in patients with hepatocellular carcinoma and underlying liver cirrhosis,or in patients with colorectal liver metastasis,IOUS allows the performance of the so-called "radical but conservative surgery",which is the pivotal factor to offer a chance of cure to an increasing proportion of patients,who until few years ago were considered only for palliative care.Using some new IOUS-guided surgical maneuvers,which are based on the liver inflow and outflow modulations,more precise anatomically subsegmental-and segmentaloriented resections can be effectively performed.The present work describes the rationale and the surgical technique for a precise tailoring of the area of hepatic resection using the most recent attainments in IOUS.Such important technical achievements should be a fundamental part of the surgical armamentarium of the modern liver surgeon.

Reply to "Application of contrast-enhanced intraoperative ultrasonography in the decision-making about hepatocellular carcinoma operation"

The use of contrast-enhanced intraoperative ultrasound for hepatocellular carcinoma has been already proposed as a novel technique to stage the disease during surgical resection. In the herein presented "letter to the editor", the authors underline some important points, which have been raised following paper published in the January issue of World Journal of Gastroenterology.

Comparison between open and laparoscopic reversal of Hartmann’s procedure for diverticulitis

AIM: To compare the open and laparoscopic Hartmann’s reversal in patients first treated for complicated diverticulitis.METHODS: Forty-six consecutive patients with diverticular disease were included in this retrospective,singlecenter study of a prospectively maintained colorectal surgery database.All patients underwent conventional Hartmann’s procedures for acute complicated diverticulitis.Other indications for Hartmann’s procedures were excluded.Patients underwent open(OHR) or laparoscopic Hartmann’s reversal(LHR) between 2000 and 2010,and received the same pre-and post-operative protocols of cares.Operative variables,length of stay,short-(at 1 mo) and long-term(at 1 and 3 years) postoperative complications,and surgery-related costs were compared between groups.RESULTS: The OHR group consisted of 18 patients(13 males,mean age ± SD,61.4 ± 12.8 years),and the LHR group comprised 28 patients(16 males,mean age 54.9 ± 14.4 years).The mean operative time and the estimated blood loss were higher in the OHR group(235.8 ± 43.6 min vs 171.1 ± 27.4 min;and 301.1 ± 54.6 mL vs 225 ± 38.6 mL respectively,P = 0.001).Bowel function returned in an average of 4.3 ± 1.7 d in the OHR group,and 3 ± 1.3 d in the LHR group(P = 0.01).The length of hospital stay was significantly longer in the OHR group(11.2 ± 5.3 d vs 6.7 ± 1.9 d,P 【 0.001).The 1 mo complication rate was 33.3% in the OHR(6 wound infections) and 3.6% in the LHR group(1 hemorrhage)(P = 0.004).At 12 mo,the complication rate remained significantly higher in the OHR group(27.8% vs 10.7%,P = 0.03).The anastomotic leak and mortality rates were nil.At 3 years,no patient required re-intervention for surgical complications.The OHR procedure had significantly higher costs(+56%) compared to the LHR procedure,when combining the surgery-related costs and the length of hospital stay.CONCLUSION: LHR appears to be a safe and feasible procedure that is associated with reduced hospitality stays,complication rates,and costs compared to OHR.

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases

Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.