Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

Pancreatic neuroendocrine tumor(P-NET) is rare and slow-growing. Current classifications predict its progno-sis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of pa-tients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indi-cated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally con-ceived as an ideal therapy for unresectable liver metas-tases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases.     

Portopulmonary hypertension in liver transplant candidates

Pulmonary vascular disorders including portopulmonary hypertension(PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure(PAP) and liver transplant surgery, survival of patients with Po PHT and advanced liver disease is significantly improved. Because of the prognostic significance of Po PHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild Po PHT can safely undergo liver transplant surgery. In cases of moderate to severe Po PHT, right heart catheterization(RHC) should be performed. In patients with moderate to severe Po PHT on RHC(mean PAP 35-45 mm Hg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed.     

New insights into the coagulopathy of liver disease and liver transplantation

INTRODUCTION The liver plays several key roles in blood coagulation being involved in both primary and secondary hemostasis[1]. It is the site of synthesis of all coagulation factors and their inhibitors except for von Willebrand factor (vWf)[2]. Liver da…     

肝移植术后早期肝功能的动态变化及其对预后的价值

目的动态观察肝移植术后1周内肝功能的变化,明确变化规律及术式对其的影响,以筛选对判断预后有价值的指标。方法回顾性分析149例肝移植受者术前、术后1、3、7d时ALT、AST、总胆红素(TB)、直接胆红素(DB)及凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原的变化情况,采用logistic回归筛选与预后有关的指标。结果肝移植术后1个月内生存的患者在术后1周内肝功能呈单峰变化。术后1d,纤维蛋白原恢复;术后3d,PT、APTT恢复;术后7d,ALT、AST下降至正常值附近。术后1个月内死亡的患者胆红素出现双峰,PT、APTT高峰前移,各项指标恢复时间延迟。背驮式肝移植受者前期恢复慢于经典式受者,但在术后1周内两组均可恢复,且术式与预后无关。术后7d的AST水平,术前及术后1、3、7d的TB水平,术后1、3d的DB水平及术后1d的PT值与预后相关。结论肝移植术后1周内肝功能出现单峰改变,术后7d基本可恢复正常;肝移植术后1周内AST、TB、PT与术后早期预后相关。术后高峰形状及位置改变提示并发症的出现,对术后管理和判断预后有积极意义。     

Ex-situ liver surgery without veno-venous bypass

AIM:To evaluate the results of hepatic resection with ex-situ hypothermic perfusion and without veno-venous bypass.METHODS:In 3 patients with liver tumor,the degree of the inferior vena cava and/or main hepatic vein involvement was verified when the liver was dissociated in the operation.It was impossible to resect the tumors by the routine hepatectomy,so the patients underwent ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.All surgical procedures were carried out or supervised by a senior surgeon.A retrospective analysis was performed for the prospectively collected data from patients with liver tumor undergoing ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.We also compared our data with the 9 cases of Pichlmayr's group.RESULTS:Three patients with liver tumor were analysed.The first case was a 60-year-old female with a huge haemangioma located in S1,S4,S5,S6,S7 and S8 of liver;the second was a 64-year-old man with cholangiocarcinoma in S1,S2,S3 and S4 and the third one was a 55-year-old man with a huge cholangiocarcinoma in S1,S5,S7 and S8.The operation time for the three patients were 6.6,6.4 and 7.3 h,respectively.The anhepatic phases were 3.8,2.8 and 4.0 h.The volume of blood loss during operation were 1200,3100,2000 mL in the three patients,respectively.The survival periods without recurrence were 22 and 17 mo in the first two cases.As for the third case complicated with postoperative hepatic vein outflow obstruction,emergency hepatic vein outflow extending operation and assistant living donor liver transplantation were performed the next day,and finally died of liver and renal failure on the third day.Operation time(6.7 ± 0.47 h vs 13.7 ± 2.6 h) and anhepatic phase(3.5 ± 0.64 h vs 5.7 ± 1.7 h) were compared between Pichlmayr's group and our series(P = 0.78).CONCLUSION:Ex-situ liver resection and liver autotransplantation has shown a potential for treatment of complicated hepatic neoplasms that are unresectable by traditional procedures.     

Multisciplinary management of patients with liver metastasis from colorectal cancer

Colorectal cancer(CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent(25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twentythirty per cent(20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and antiEGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases.     

脾切除术后抗病毒治疗对肝硬化患者肝脏储备及再出血风险的影响

目的评价脾切除术后抗病毒治疗对丙肝肝硬化患者肝脏储备及再出血风险的影响。方法收集长期随访资料完整的肝硬化脾切除患者的资料纳入回顾性统计分析。依照术后不同治疗方式分为两组:治疗组为抗病毒治疗42例和对照组为未抗病毒治疗33例。分别在治疗过程中6个不同时间点对各组患者凝血系列(APTT、PT、PTA、Fib)、肝脏功能(ALB、A/G)、PLT及门静脉宽度等主要指标进行统计分析。结果 PT在治疗组中的表达于术后60个月较抗病毒治疗前显著降低(P0.01),延缓了PT时间;APTT在治疗组和对照组术后均即刻出现下降(P0.05),但这种下降趋势于治疗组可保持到术后60个月,而对照组自术后6个月以后呈上升趋势;治疗组对PTA短期无改善,但术后60个月时较对照组差异有统计学意义(P0.01);术后6个月时治疗组和对照组Fib值均为最高点,但治疗组与各时间点差异均无统计学意义;PLT在术后即刻升高且与术前比较差异有统计学意义(P0.001),并随病程延长出现与ALB水平和A/G比值相同的先升后降趋势。治疗组较对照组能够使术后降低的门静脉宽度值和出血率延缓上升。结论肝硬化患者脾切除术后进行抗病毒治疗能够显著改善患者的凝血功能,降低再出血风险。     

内镜下乳头切开术与外科手术治疗胆总管结石合并肝硬化的回顾性分析

目的探讨内镜下乳头切开术（EST）与外科手术治疗胆总管结石合并肝硬化病例疗效及并发症情况的比较。方法1985年8月至2008年5月间,胆总管结石合并肝硬化患者中139例行EST术,98例行外科手术作为对照组。结果EST组和外科手术组取石成功率分别为95％和100％。术后并发症发生率EST组为16．5％,外科手术组为62．2％;术后死亡率EST组为5．O％,外科手术组为24．5％,两组差异均有统计学意义。并发症发生率与肝功能Child—Pugh分级关系：A级,两组比较差异无统计学意义,而B级与C级,两组比较差异有统计学意义。死亡率与肝功能Child-Pugh分级关系：A级与B级,两组比较差异无统计学意义,而C级,两组比较差异有统计学差异。结论与外科手术相比,EST治疗胆总管结石合并肝硬化可显著减少术后并发症发生率和死亡率,取石成功率高达95％。     

Application of stapling devices in liver surgery: Current status and future prospects

The liver is a vascular-rich solid organ. Safe and effective dissection of the vessels and liver parenchyma, and control of intraoperative bleeding are the main concerns when performing liver resection. Several studies have confirmed that intraoperative blood loss and postoperative transfusion are predictors of postoperative morbidity and mortality in liver surgery. Various methods and instruments have been developed during hepatectomy. Stapling devices are crucial for safe and rapid anastomosis. They are used to divide hepatic veins and portal branches, and to transect liver parenchyma in open liver resection. In recent years, laparoscopic liver surgery has developed rapidly, and is now preferred by many surgeons. Stapling devices have also been gradually introduced in laparoscopic liver surgery, from dividing vascular and biliary structures to parenchymal transection. This may be because staplers make manipulation more simple, rapid and safe. Even in single incision laparoscopic surgery, which is recognized as a new minimally invasive technique, staplers are also utilized, especially in left lateral hepatectomy. For safe application of stapling devices in liver surgery, more related designs and modifications, such as application of a suitable laparoscopic articulating liver tissue crushing device, a staple line reinforcement technique with the absorbable polymer membrane or radiofrequency ablation assistance, are still needed. More randomized studies are needed to demonstrate the benefits and find broader indications for the use of stapling devices, to help expand their application in liver surgery.     

Therapy of central pontine myelinolysis following living donor liver transplantation： Report of three cases

We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine myelinolysis following living donor liver transplantation from January 2005 to November 2007 were retrospectively analyzed at the West China Hospital, Sichuan University, China. The three patients developed hyponatremia prior to surgery. Case 1 suffered locked-in syndrome following surgery, and received a large dose of gamma globulin, and subsequently recovered. Case 2 was in a coma for three days, and received hyperbaric chamber treatment. This patient remained in a mild coma for six months following surgery. Case 3 developed consciousness disturbances, gradually went into a coma following surgery, and died due to pulmonary infection. Central pontine myelinolysis is a severe complication in patients following living donor liver transplantation. Largedose gamma globulin treatment, as well as hyperbaric oxygen, might be effective therapeutic methods.     

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM:To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.METHODS:A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010.Regeneration was evaluated by multidetector computed tomographyat a mean follow-up of 43.85 d.The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation,and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data.Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.RESULTS:Ten of the 27 patients(37%)underwent chemotherapy prior to surgery,with a statistically significant prevalence of patients with metastasis(P=0.007).Eight patients(30%)underwent embolization,3 with primary tumors,and 5 with secondary tumors.Twenty patients(74%)experienced complications,with 12(60%)experiencing Clavien-Dindo Grade 3a to 5 complications.Regeneration≥100%occurred in 10(37%)patients.The predictors were smaller future remnant liver volume(-0.002;P<0.001),and a greater spleen volume/future remnant liver volume ratio(0.499;P=0.01).Patients with a resection of≥5 Couinaud segments experienced greater early regeneration(P=0.04).Nine patients experienced surgical site infections,and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected(P=0.016).There were no significant differences between patients with primary or secondary tumors,and either onset or infections or severity of surgical complications.CONCLUSION:Regardless of the onset of infective complications,future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.     

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several significant concerns. Liver resection is the most important treatment for colorectal liver metastases. The definition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with definitely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluating and predicting the efficacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.     

Prognostic value of disseminated colorectal tumor cells in the liver: results of follow-up examinations

Background and aims Dissemination of tumor cells is an initial step in metastatic disease. Detection of disseminated tumor cells (DTC) in blood, bone marrow and lymph nodes has been associated with reduced disease-free survival, but to date there are no data for hepatic DTC. We investigated the prognostic relevance of hepatic DTC that are present in patients with colorectal cancer (CRC) at the time of surgery.Patients and methods In 121 patients with CRC clinically diagnosed for liver metastasis by ultrasound, CT, and exploration during surgery DNA from liver biopsy specimens obtained during surgery was examined by a PCR-RFLP assay for K-ras mutations as a marker for DTC. At the time of surgery 54 of the 121 were mutated in K-ras codons 12 or 13. After a median follow-up of 405 days all survivors were reevaluated by ultrasound/CT.Results Patients with a K-ras mutation in their primary tumor had a significantly lower probability of survival and higher risk of harboring a synchronous second colorectal carcinoma than patients with a K-ras wild-type tumor. Based on specimens taken intraoperatively DTC were found in the liver of 14 of 54 patients (26%). At follow-up only 10 of 40 patients (25%) with DTC-free liver had died of their disease but 9 of the 14 patients with hepatic DTC. Among the 14 patients with hepatic DTC 10 (71%) had developed new liver metastasis, compared to 12 of 40 (30%) in those without hepatic DTC.Conclusion Hepatic DTC in colorectal cancer patients is associated with reduced overall survival and increased risk of hepatic metastasis development. Further studies are necessary to corroborate our results since the number of patients studied is still limited.U. Linnemann and C.C. Schimanski contributed equally to this work     

吲哚菁绿清除试验在结直肠癌肝转移患者化疗性肝损伤评估中的作用

手术是目前结直肠癌肝转移患者获得生存延长的最佳治疗手段,临床实践中多数结直肠癌肝转移患者需要术前化疗,而化疗性肝损伤的严重程度及其对围术期安全性的影响亟须精确评估。吲哚菁绿（ICG）清除试验是肝储备功能定量检测的手段之一。对于肝硬化造成永久性的肝损伤,ICG试验可以精准地反映其肝储备功能的异常。但ICG试验能否反映化疗性肝损伤对肝储备功能的影响尚存在争议。本综述将从ICG试验反映肝储备功能的原理、应用及ICG指标异常与化疗性肝损伤有无和严重程度的相关性,以及与肝切除安全性的关系和ICG指标的影响因素等多个角度进行文献归纳总结,探讨ICG试验在化疗性肝损伤的评估中的作用。     

肝癌肝移植转化治疗策略进展

肝移植能够在彻底去除肿瘤的同时完整移除病肝,对于合并肝硬化的肝癌患者是最佳选择。近年来,随着肝癌综合治疗研究的进展,转化治疗理念被引入肝癌外科治疗领域以及肝移植领域,成功的转化治疗有望将超出标准肝癌患者转变为符合标准而接受肝移植手术,从而极大改善其预后。就肝癌肝移植转化治疗的进展进行简要介绍。     

肝硬化的手术与细胞治疗

肝硬化是由一种或多种病因长期或反复作用形成的弥漫性肝损害。肝移植是治疗失代偿期肝硬化的有效方法,但是由于肝源紧张等因素,多数肝硬化患者因上消化道出血、肝性脑病、继发感染、癌变等并发症危及生命。干细胞治疗可以改善肝硬化,自体骨髓经门静脉移植到肝脏,更有利于干细胞在肝内的存活和增殖。对150多例失代偿期肝硬化患者做自体骨髓经门静脉移植,结果显示肝功能好转,肝脏体积增大,弹性超声检查提示肝脏硬度减低。     

Prealbumin is predictive for postoperative liver insufficiency in patients undergoing liver resection

AIM: To investigate the risk factors for postoperative liver insufficiency in patients with Child-Pugh class A liver function undergoing liver resection.METHODS: A total of 427 consecutive patients undergoing partial hepatectomy from October 2007 to April 2011 at a single center (Department of Hepatic SurgeryI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China) were included in the study. All the patients had preoperative liver function of Child-Pugh class A and were diagnosed as having primary liver cancer by postoperative histopathology. Surgery was performed by the same team and hepatic resection was carried out by a clamp crushing method. A clamp/unclamp time of 15 min/5 min was adopted for hepatic inflow occlusion. Patients’ records of demographic variables, intraoperative parameters, pathological findings and laboratory test results were reviewed. Postoperative liver insufficiency and failure were defined as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak, clinically apparent ascites, prolonged coagulopathy requiring frozen fresh plasma, and/or hepatic encephalopathy. The incidence of postoperative liver insufficiency or liver failure was observed and the attributing risk factors were analyzed. A multivariate analysis was conducted to determine the independent predictive factors.RESULTS: Among the 427 patients, there were 362 males and 65 females, with a mean age of 51.1 ± 10.4 years. Most patients (86.4%) had a background of viral hepatitis and 234 (54.8%) patients had liver cirrhosis. Indications for partial hepatectomy included hepatocellular carcinoma (391 patients), intrahepatic cholangiocarcinoma (31 patients) and a combination of both (5 patients). Hepatic resections of ≤ 3 and ≥ 4 liver segments were performed in 358 (83.8%) and 69 (16.2%) patients, respectively. Seventeen (4.0%) patients developed liver insufficiency after hepatectomy, of whom 10 patients manifested as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak, 6 patients had clinically apparent ascites and prolonged coagulopathy, 1 patient had hepatic encephalopathy and died on day 21 after surgery. On univariate analysis, age ≥ 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency (P = 0.045 and P = 0.009, respectively). There was no statistical difference in postoperative liver insufficiency between patients with or without hepatitis, liver cirrhosis and esophagogastric varices. Intraoperative parameters (type of resection, inflow blood occlusion time, blood loss and blood transfusion) and laboratory test results were not associated with postoperative liver insufficiency either. Age ≥ 60 years and prealbumin < 170 mg/dL were selected on multivariate analysis, and only prealbumin < 170 mg/dL remained predictive (hazard ratio, 3.192; 95%CI: 1.185-8.601, P = 0.022).CONCLUSION: Prealbumin serum level is a predictive factor for postoperative liver insufficiency in patients with liver function of Child-Pugh class A undergoing hepatectomy. Since prealbumin is a good marker of nutritional status, the improved nutritional status may decrease the incidence of liver insufficiency.     

Transoesophageal echocardiography during liver transplantation

Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.     

Total laparoscopic liver resection in 78 patients

AIM: To summarize the clinical experience of laparoscopic hepatectomy at a single center.METHODS: Between November 2003 and March 2009, 78 patients with hepatocellular carcinoma ( n = 39), metastatic liver carcinoma ( n = 10), and benign liver neoplasms ( n = 29) underwent laparoscopic hepatectomy in our unit. A retrospective analysis was done on the clinical outcomes of the 78 patients.RESULTS: The lesions were located in segments Ⅰ ( n = 3), Ⅱ ( n = 16), Ⅲ ( n = 24), Ⅳ ( n = 11), Ⅴ ( n = 11),Ⅵ ( n = 9), and Ⅷ ( n = 4). The lesion sizes ranged from 0.8 to 15 cm. The number of lesions was three ( n = 4),two ( n = 8) and one ( n = 66) in the study cohort. The surgical procedures included left hemi-hepatectomy ( n = 7), left lateral lobectomy ( n = 14), segmentectomy ( n = 11), local resection ( n = 39), and resection of metastatic liver lesions during laparoscopic surgery for rectal cancer ( n = 7). Laparoscopic liver resection was successful in all patients, with no conversion to open procedures. Only four patients received blood transfusion (400-800 mL). There were no perioperative complications, such as bleeding and biliary leakage. The liver function of all patients recovered within 1 wk, and no liver failure occurred.CONCLUSION: Laparoscopic hepatectomy is a safe and feasible operation with minimal surgical trauma. It should be performed by a surgeon with sufficient experience in open hepatic resection and who is proficient in laparoscopy.     

Liver transplantation in acute liver failure:A challenging scenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, intervalbetween jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.