Surgical treatment of liver metastases from non-colorectal non-neuroendocrine carcinomas.

INTRODUCTION: In the literature, results after surgical treatment of non-colorectal non-neuroendocrine liver metastases (NCNNLM) are reported that are often inferior to those from colorectal liver metastases. The selection of patients with favorable tumor biology is currently still a matter of discussion. MATERIALS/METHODS: The retrospective data analysis was based on data that were collected for the multicenter study "Role of surgical treatment for non-colorectal liver metastases" in county Thuringia. RESULTS: For the study, 637 patients were included from 1995 to 2018. 5 and 10-year survival of R0 resected patients were 33% and 19%, respectively. In the multi-variate analysis of the entire group, sex, timing, disease-free interval, number of metastases, R-classification as well as lymph node status of the primary lesion showed an independent statistical influence on the 5-year survival. In the group of R0 resected patients, disease-free interval, number of metastases and lymph node status of the primary lesion influenced the 5-year survival in the multi-variate analysis. In kidney malignancies, R-classification, timing and number of liver metastases were statistically significant in the multi-variate analysis of the 5-year survival, in mamma carcinomas only the R-classification. CONCLUSION: The Adam score identifies some risk factors which influence prognosis in most but not in all tumor entities. For kidney cancer and breast cancer it can be simplified.

Optimal hepatic surgery: Are we making progress in North America?

BACKGROUND: The aim of this analysis was to determine whether optimal outcomes have increased in recent years. Hepatic surgery is high risk, but regionalization and minimally invasive approaches have evolved. Best practices also have been defined with the goal of improving outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried. Analyses were performed separately for partial (≤2 segments), major (≥3 segments), and all hepatectomies. Optimal hepatic surgery was defined as the absence of mortality, serious morbidity, need for a postoperative invasive procedure or reoperation, prolonged length of stay (<75th percentile) or readmission. Tests of trend, χ2, and multivariable analyses were performed. RESULTS: From 2014 to 2018, 17,082 hepatectomies, including 11,862 partial hepatectomies and 5,220 major hepatectomies, were analyzed. Minimally invasive approaches increased from 25.6% in 2014 to 29.6% in 2018 (P < .01) and were performed more frequently for partial hepatectomies (34.2%) than major hepatectomies (14.4%) (P < .01). Operative time decreased from 220 minutes in 2014 to 208 minutes in 2018 (P < .05) and was lower in partial hepatectomies (189 vs 258 minutes for major hepatectomies) (P < .01). Mortality (0.7%) and length of stay (4 days) were lower for partial hepatectomies compared with major hepatectomies (1.9%; 6 days), and length of stay decreased for both partial hepatectomies (5 days in 2014 to 4 days in 2018) and major hepatectomies (6 days in 2014 to 6 days in 2018) (all P < .01). Postoperative sepsis (2.9% in 2014 and 2.4% in 2018), bile leaks (6% in 2014 and 4.8% in 2018), and liver failure (3.7% in 2014 and 3.3% in 2018) decreased for all patients (<.05). On multivariable analyses, overall morbidity decreased for major hepatectomies (OR 0.95, 95% CI 0.91-0.99) and all hepatectomies (OR 0.97, 95% CI 0.94-0.99, both P < .01), and optimal hepatic surgery increased over time for partial hepatectomies (OR 1.05, 95% CI 1.02-1.09) and all hepatectomies (OR 1.04, 95% CI 1.02-1.07, both P < .01). CONCLUSION: Over a 5-year period in North America, minimally invasive hepatectomies have increased, while operative time, postoperative sepsis, bile leaks, liver failure, and prolonged length of stay have decreased. Optimal hepatic surgery has increased for partial and all hepatectomies and is achieved more often in partial than in major resections.

The evolution of surgery for colorectal liver metastases: A persistent challenge to improve survival.

Only a few decades ago, the opinion that colorectal liver metastases were a palliative diagnosis changed. In fact, previously, the prevailing view was strongly resistant against resecting colorectal liver metastases. Constant technical improvement of liver surgery and, much later, effective chemotherapy allowed for a successful wider application of surgery. The clinical use of portal vein embolization was the starting signal of regenerative liver surgery, where insufficient liver volume can be expanded to an extent where safe resection is possible. Today, a number of these techniques including portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and bi-embolization (portal and hepatic vein) can be successfully used to address an insufficient future liver remnant in staged resections. It turned out that the road to success is embedding surgery in a well-orchestrated oncological concept of controlling systemic disease. This concept was the prerequisite that meant liver transplantation could enter the treatment strategy for colorectal liver metastases, ending up with a 5-year overall survival of 80% in highly selected cases. In particular, techniques combining principles of 2-stage hepatectomy and liver transplantation, such as "resection and partial liver segment 2-3 transplantation with delayed total hepatectomy" (RAPID) are on the rise. These techniques enable the use of partial liver grafts with primarily insufficient liver volume. All this progress also prompted a number of innovative local therapies to address recurrences ultimately transferring colorectal liver metastases from instantly deadly into a chronic disease in some cases.

Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.

Trends and outcomes of simultaneous versus staged resection of synchronous colorectal cancer and colorectal liver metastases.

BACKGROUND: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases. METHODS: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching. RESULTS: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; ptrend = 0.02). After propensity score matching (n = 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P = .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P = .002) yet comparable 90-day mortality (3.5% vs 1.0%; P = .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; ptrend = 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P = .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy. CONCLUSION: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases.

Robotic Liver Surgery - Current Standards and Future Perspectives.

BACKGROUND: Robotic liver surgery is emerging as the future of minimal invasive surgery. The robotic surgical system offers a stable camera platform, elimination of physiologic tremor, augmented surgical dexterity as well as improved ergonomics because of a seated operating position. Due to the theoretical advantages of the robotic assisted system, complex liver surgery might be an especially interesting indication for a robotic approach since it demands delicate tissue dissection, precise intracorporeal suturing as well as difficult parenchymal transection with subsequent need for meticulous hemostasis and biliostasis. MATERIAL AND METHODS: An analysis of English and German literature on open, laparoscopic and robotic liver surgery was performed and this review provides a general overview of the existing literature along with current standards and aims to specifically point out future directions of robotic liver surgery. RESULTS: Robotic liver surgery is safe and feasible compared to open and laparoscopic surgery, with improved short-term postoperative outcomes and at least non-inferior oncological outcomes. CONCLUSION: In complex cases including major hepatectomies, extended hepatectomies with biliary reconstruction and difficult segmentectomies of the posterior-superior segments, robotic surgery appears to emerge as a reasonable alternative to open surgery rather than being an alternative to laparoscopic procedures.

Extended liver resection in mice: state of the art and pitfalls-a systematic review.

BACKGROUND: Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases. METHODS: A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy. RESULTS: The Boolean search found 3741 articles on Pubmed, with 3130 publications remaining when filtered by language and the presence of a full text. In total, 21 of these publications examined the key themes of the animal model described. The mortality varied from 0 to 50% depending on the surgeon's experience and the resection method. The liver resection was mainly performed with classic sutures (14 out of 21 publications) and isoflurane was used for anaesthesia (10 out of 21 publications) in combination with analgesics (buprenorphine or ketamine/xylazine). The most used mouse strain was C57BL/6 (7 of 21 publications) which was on average 11 weeks old with a weight of 23 g. CONCLUSION: Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.

Systematic failure to operate on colorectal cancer liver metastases in California.

BACKGROUND: Despite evidence that liver resection improves survival in patients with colorectal cancer liver metastases (CRCLM) and may be potentially curative, there are no population-level data examining utilization and predictors of liver resection in the United States. METHODS: This is a population-based cross-sectional study. We abstracted data on patients with synchronous CRCLM using California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning Inpatient Database. Quantum Geographic Information System (QGIS) was used to map liver resection rates to California counties. Patient- and hospital-level predictors were determined using mixed-effects logistic regression. RESULTS: Of the 24 828 patients diagnosed with stage-IV colorectal cancer, 16 382 (70%) had synchronous CRCLM. Overall liver resection rate for synchronous CRCLM was 10% (county resection rates ranging from 0% to 33%) with no improvement over time. There was no correlation between county incidence of synchronous CRCLM and rate of resection (R2  = .0005). On multivariable analysis, sociodemographic and treatment-initiating-facility characteristics were independently associated with receipt of liver resection after controlling for patient disease- and comorbidity-related factors. For instance, odds of liver resection decreased in patients with black race (OR 0.75 vs white) and Medicaid insurance (OR 0.62 vs private/PPO); but increased with initial treatment at NCI hospital (OR 1.69 vs Non-NCI hospital), or a high volume (10 + cases/year) (OR 1.40 vs low volume) liver surgery hospital. CONCLUSION: In this population-based study, only 10% of patients with liver metastases underwent liver resection. Furthermore, the study identifies wide variations and significant population-level disparities in the utilization of liver resection for CRCLM in California.

Liver resection in Cirrhotic liver: Are there any limits?

Liver resection remains one of the most technically challenging surgical procedure in abdominal surgery due to the complex anatomical arrangement in the liver and its rich blood supply that constitutes about 20% of the cardiac output per cycle. The challenge for resection in cirrhotic livers is even higher because of the impact of surgical stress and trauma imposed on borderline liver function and the impaired ability for liver regeneration in cirrhotic livers. Nonetheless, evolution and advancement in surgical techniques as well as knowledge in perioperative management of liver resection has led to a substantial improvement in surgical outcome in recent decade. The objective of this article was to provide updated information on the recent developments in liver surgery, from preoperative evaluation, to technicality of resection, future liver remnant augmentation and finally, postoperative management of complications.

Current status of liver transplantation in Asia.

In spite of early adoption of the brain death legislation, and all efforts at promoting deceased donation, various social, economic and cultural factors have acted as road blocks to the furthering of deceased donor liver transplantation (DDLT) in most Asian societies. On the other hand, Asian liver transplant centers have been the pioneers, innovators, and technical advancement catalysts for the world to follow, especially with regards to living donor liver transplantation (LDLT). With some high volume centers performing more than 200 LDLTs a year with good outcomes in the donor and recipient, techniques to expand the living donor pool have also been adopted like ABO-incompatible, paired exchange and dual lobe living donor liver transplants. Although large multicenter, and registry data as regards safety and outcomes of minimally invasive donor hepatectomy are awaited, expert centers have pioneered, and now regularly perform purely laparoscopic and robotic living donor hepatectomies, especially in Korea.

Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience.

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63-75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5 years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

[The progresses of liver resection for solitary large hepatocellular carcinoma].

Large hepatocellular carcinoma (HCC) is one of the most common malignancies and was mistaked as "advanced and unresectable" . Liver resection is still the best curable treatment for HCC.The resection of large HCC is very difficult, which seriously restrict the progress of liver surgery.Our study proved that solitary large HCC (SLHCC) has unique clinicopathological and molecular biological characteristics.No matter how big the tumor size is, it belongs to early stage if there is no vascular invasion.Liver resection should be aggressively recommended for the patients with SLHCC, in which they can obtain good outcome, with 40% 5-year survival rate.We has also defined the borderline resectable hepatocellular carcinoma, and suggested that strictly master and correctly judge the surgical indications, syntheticly evaluate the surgical safety and patient's tolerability for liver resection.After that, with hands of experienced surgeons, liver resection for SLHCC can be safely and reliablely performed.

Ubiquitin-Specific Protease 22/Silent Information Regulator 1 Axis Plays a Pivotal Role in the Prognosis and 5-Fluorouracil Resistance in Hepatocellular Carcinoma.

BACKGROUND: Ubiquitin-specific protease 22 (USP22) is described as a key subunit of the Spt-Ada-Gcn5 acetyl transferase complex, which plays an important role in the prognosis and resistance to chemotherapy drugs in hepatocellular carcinoma (HCC). Silent information regulator 1 (SIRT1) is a member of the sirtuin family that is deubiquitinated by USP22. However, it is still unknown whether USP22 and SIRT1 co-expression is associated with disease progression and 5-Fluorouracil (5-FU) resistance in HCC. METHODS: 141 patients who received hepatectomy at our hospital from January 2010 to December 2014 were enrolled in this study. The expression of USP22 and SIRT1 was detected by immunohistochemical staining. Clinicopathological features, including age, gender, tumor number, tumor size, tumor differentiation, tumor stage, alpha-fetoprotein and microscopic vascular invasion, were assessed. Further experiments confirmed the role of SIRT1 in 5-FU drug resistance in vivo. RESULTS: Immunohistochemical staining showed that the high expression of USP22 and SIRT1 was frequently observed in HCC tissues relative to normal liver tissues. Overexpression of USP22 is associated with microscopic vascular invasion (MVI). Further analysis showed that the co-expression of USP22 and SIRT1 was more effective in predicting the prognosis of HCC. The SIRT1 inhibitor EX-527 dramatically inhibited the expression of Cyclin B1 and resistance-associated protein 3 (MRP3) to reduce 5-FU drug resistance in vivo. CONCLUSION: These findings suggest that the co-expression of USP22 and SIRT1 is significantly associated with unfavorable HCC progression. The inhibition of SIRT1 in vivo could be valuable in improving 5-FU drug sensitivity and inhibiting tumor cell proliferation and inducing apoptosis.

Right anatomical hepatectomy: pioneers, evolution, and the future.

To identify the pioneers of right anatomical hepatectomy (RAH), and clarify the development of associated operative procedures, concepts, and the future, we reviewed the "hidden" literature published in Eastern and Western countries since the 1940s. We searched the English and non-English literature on RAH through web search engines, text books and documents, and also referred to experts' comments. Non-English literature, other than in Japanese, was translated. Changes in the anatomical concept, anatomical identification, vascular control technique, approaches, pre-operative management, and other aspects of RAH were analyzed. Honjo and Lortat-Jacob, in 1949 and 1951, respectively, reported the first cases of successful RAH; since then, RAH has been used in the treatment of liver malignancies worldwide. Vascular in-flow control is divided into intrafascial, extrafascial or transfissual access. The anatomical border along the main hepatic veins was proposed for transection, and anterior approaches have been suggested as alternative options in the hazardous situation of right liver rotation. In the laparoscopic era, several procedures and positions have been devised for RAH. In summary, RAH and related anatomical hepatectomy have been established as treatment methods for 70 years, and the future of RAH includes new concepts, approaches, and techniques to optimize patient safety and disease curability.

Recent advances in surgical strategies for alveolar echinococcosis of the liver.

Liver resection is the safest intervention for alveolar echinococcosis (AE), because the only potentially curative treatment is complete removal of the lesion. In combination with medical anthelmintic treatment, a safe distance of at least 1 mm is permissible in this procedure. Even when liver resection does not cure AE, good long-term survival outcomes can be achieved if most of the lesion has been removed and the disease is controlled with lifelong benzimidazole treatment. If the residual lesion is comparatively small and does not contain a closed space that may adhere to the surrounding tissue and form an abscess, complications such as sepsis arising from an abscess on the cut surface can be prevented and the required biliary drainage might be relatively simple. Larger AE lesions that invade the inferior vena cava can be treated effectively with the recent advances in reduction surgical techniques. An effective concentration of albendazole (ABZ) is found only in the periphery of AE lesions, because this drug penetrates the lesions passively. Liver transplantation, with adjuvant ABZ and the administration of appropriate immunosuppressive agents such as cyclosporin A, is indicated for patients with end-stage AE.

Outcomes of laparoscopic repeat liver resection for recurrent liver cancer: A system review and meta-analysis.

BACKGROUND: With the improvements of surgical instruments and surgeons' experience, laparoscopic liver resection has been applied for recurrent tumors. However, the value of laparoscopic repeat liver resection (LRLR) is still controversial nowadays, which compelled us to conduct this meta-analysis to provide a comprehensive evidence about the efficacy of LRLR for recurrent liver cancer. METHODS: A computerized search was performed to identify all eligible trials published up to April 2019. This meta-analysis was conducted to estimate the perioperative data and oncological outcomes of LRLR by compared with open repeat liver resection (ORLR) and laparoscopic primary liver resection (LPLR). A fixed or random-effect modal was established to collect the data. RESULTS: A total of 1232 patients were included in this meta-analysis (LRLR: n = 364; ORLR: n = 396; LPLR: n = 472). LRLR did not increase the operative time compared to ORLR (WMD = 15.92 min; 95%CI: -33.53 to 65.37; P = .53). Conversely, LRLR for patients with recurrent tumors was associated with less intraoperative blood loss (WMD = -187.33 mL; 95%CI: -249.62 to -125.02; P < .00001), lower transfusion requirement (OR = 0.24; 95%CI: 0.06-1.03; P = .05), fewer major complications (OR = 0.42; 95%CI: 0.23-0.76; P = .004), and shorter hospital stays (WMD = -2.31; 95%CI: -3.55 to -1.07; P = .0003). In addition, the oncological outcomes were comparable between the two groups. However, as for the safety of LRLR compared with LPLR, although the operative time in LRLR group was longer than LPLR group (WMD = 58.63 min; 95%CI: 2.99-114.27; P = .04), the blood loss, transfusion rates, R0 resection, conversion, postoperative complications, and mortality were similar between the two groups. CONCLUSIONS: LRLR for recurrent liver cancer could be safe and feasible in selected patients when performed by experienced surgeons.

Chemotherapeutic doses of arsenic trioxide delays hepatic regeneration by oxidative stress and hepatocyte apoptosis in partial hepatectomy rat.

The extensive regeneration potential of the liver makes use of hepatic re-sectioning and split liver transplantation for treating advanced liver diseases. Heavy metals such as cisplatin, carboplatin, and arsenic trioxide (ATO) are being practiced as chemotherapeutic agents for different cancers. Further, research is progressed on using different heavy metal nano-particles as a drug, drug carrier and diseases detective agent. Since liver is the chief organ metabolize ingested materials, the current study focuses on the involvement of ATO on acute liver injury regeneration using a partially hepatectomised (PHx) rat model. Scrutiny of serum liver markers such as albumin, AST, ALT & ALP and hepatic antioxidants like reduced glutathione, glutathione peroxidase, glutathione S-transferase, catalase & superoxide dismutase reveled ATO mediated hepatocyte injury and oxidative stress. Further, oxidative stress is confirmed with elevated TBARS and 8-OHdG in the hepatocyte nucleus in ATO supplemented healthy and regenerating liver and are co-relating with the H&E histological observations. It is noticed that ATO supplementation reduced liver regeneration potential as evidenced by reduced proliferative markers (Ki-67 and PCNA) and meanwhile increases apoptotic protein PARP-1. ICP-MS analysis displayed several-fold hiked serum and liver arsenic in ATO administrated normal and liver regenerating animals. This study concludes that ATO at a chemotherapeutic concentration augments oxidative stress and hepatocytes apoptosis, thereby delays liver regeneration potential and could affect the outcome of liver transplantation.

[Current status and prospect of surgical treatment of liver cancer].

With the rapid development of liver surgery,minimally invasive techniques have been widely used in liver surgery. Many challenging liver can be performed laparoscopically to decrease the surgical trauma. At the same time,the efficiency and accuracy of liver surgeries have been highly improved by the advanced assisted technology of liver surgery. The purpose of this article is to summarize the current situation of liver surgery as well as the future of liver surgery.