Go Wakabayashi

The International Position on Laparoscopic Liver Surgery: The Louisville Statement, 2008

Objective:To summarize the current world position on laparoscopic liver surgery. Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery. Methods:On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training. Results:The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection. Conclusions:Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.

Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka.

OBJECTIVE This review aims to assess the impact of implementing dedicated emergency surgical services, in particular acute care surgery, on clinical outcomes. BACKGROUND The optimal model for delivering high-quality emergency surgical care remains unknown. Acute Care Surgery (ACS) is a health care model combining emergency general surgery, trauma, and critical care. It has been adopted across the United States in the management of surgical emergencies. METHOD A systematic review was performed after PRISMA recommendations using the MEDLINE, Embase, and Psych-Info databases. Studies assessing different care models and institutional factors affecting the delivery of emergency general surgery were included. RESULTS Twenty-seven studies comprising 744,238 patients were included in this review. In studies comparing ACS with traditional practice, mortality and morbidity were improved. Moreover, time to senior review, delays to operating theater, and financial expenditure were often reduced. The elements of ACS models varied but included senior clinicians present onsite during office hours and dedicated to emergency care while on-call. Referrals were made to specialist centers with primary surgical assessments taking place on surgical admissions units rather than in the emergency department. Twenty-four-hour access to dedicated emergency operating rooms was also described. CONCLUSIONS ACS models as well as centralized units and hospitals with dedicated emergency operating rooms, access to radiology and intensive care facilities (ITU) are all factors associated with improved clinical and financial outcomes in the delivery of emergency general surgery. There is, however, no consensus on the elements that constitute an ideal ACS model and how it can be implemented into current surgical practice.

Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines

Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem‐loop‐mediated reverse transcription real‐time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR‐138, was significantly downregulated in ATC cell lines in comparison with PTC (P < 0.01). Eleven miRNA (including miR‐138) potentially targeting the human telomerase reverse transcriptase (hTERT) gene were totally downregulated in both ATC and PTC cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR‐138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = –0.392, P = 0.148). We demonstrated that overexpression of miR‐138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR‐138 and the hTERT 3′‐untranslated region by luciferase reporter assay. These results suggest that loss of miR‐138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma. (Cancer Sci 2008; 99: 280–286)

Ten‐year experience of totally laparoscopic liver resection in a single institution

Recent developments in liver surgery include the introduction of laparoscopic liver resection. The aim of the present study was to review a single institutions 10‐year experience of totally laparoscopic liver resection (TLLR).

Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma.

The functions of many long non-coding RNAs (ncRNAs) in human cancers have not yet been elucidated. The long ncRNA HOTAIR is expressed from the developmental HOXC locus located on chromosome 12q13.13. Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis. In this study, we examined the clinical significance of HOTAIR expression in patients with hepatocellular carcinoma (HCC). HOTAIR expression was detected in primary HCCs in 13 out of 64 patients. Patients with HOTAIR expression had significantly poorer prognoses and a larger primary tumor size than those without HOTAIR expression, similar to studies in breast and colorectal cancers. Moreover, introduction of human HOTAIR into liver cancer cells revealed that HOTAIR promoted more rapid proliferation compared to control cells. Thus, although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.

Interleukin-1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat

The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days. Rats were subjected to 90 min of partial liver warm ischemia by clamping the vessels of the left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to determine the effect of IL-1ra pretreatment on survival rate, after 90 min of partial liver ischemia, the right lateral and caudate lobes were excised, leaving only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. Histological evidence of tissue injury was minimal in the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared with the nontreated group. Survival rates in the IL-1ra-treated and nontreated group were 80% and 30%, respectively. The data demonstrated that the production of IL-1 and TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.

Comparative Short-term Benefits of Laparoscopic Liver Resection: 9000 Cases and Climbing.

Objective:To perform a systematic review of worldwide literature on laparoscopic liver resections (LLR) and compare short-term outcomes against open liver resections (OLR) by meta-analyses. Summary Background Data:There are no updated pooled data since 2009 about the current status and short-term outcomes of LLR worldwide. Patients and Methods:All English language publications on LLR were screened. Descriptive worldwide data and short-term outcomes were obtained. Separate analyses were performed for minor-only and major-only resection series, and series in which minor/major resections were not differentiated. Apparent case duplications were excluded. Results:A set of 463 published manuscripts were reviewed. One hundred seventy-nine single-center series were identified that accounted for 9527 LLR cases worldwide. Minor-only, major-only, and combined major–minor series were 61, 18, and 100, respectively, including 32, 8, and 43 comparative series, respectively. Of the total 9527 LLR cases reported, 6190 (65%) were for malignancy and 3337 (35%) were for benign indications. There were 37 deaths reported (mortality rate = 0.4%). From the meta-analysis comparing case-matched LLR to OLR (N = 2900 cases), there was no increased mortality and significantly less complications, transfusions, blood loss, and hospital stay observed in LLR vs OLR. Conclusions:This is the largest review of LLR available to date with over 9000 cases published. It confirms growing safety when performed in selected patients and by trained surgeons, and suggests that LLR may offer improved patient short-term outcomes compared with OLR. Improved levels of evidence, standardized reporting of outcomes, and assuring proper training are the next challenges of laparoscopic liver surgery.

Laparoscopic Major Hepatectomy: A Systematic Literature Review and Comparison of 3 Techniques

Objective: This review assesses the current status of laparoscopic liver resection. Background: The trend in laparoscopic liver resection has been moving from limited resections toward major hepatectomy. The surgical techniques for laparoscopic major hepatectomy include pure laparoscopic, hand-assisted laparoscopic, and laparoscopy-assisted methods. We performed a literature search and systematic review to assess the current status of laparoscopic major hepatectomy. Methods: Our literature review was conducted in Medline using the keywords “laparoscopy” or “laparoscopic” combined with “liver resection” or “hepatectomy.” Articles written in English containing more than 10 cases of laparoscopic major hepatectomy were selected. Results and Conclusions: Twenty-nine articles were selected for this review. The laparoscopic major hepatectomies achieved similar patient and economic outcomes compared with open liver resections in selected (noncirrhotic) patients. Surgeon experience with the techniques affected the results; thus, a learning period is mandatory. Of these 3 techniques, the pure laparoscopic method is suitable for experienced surgeons to achieve better cosmetic outcomes, whereas the hand-assisted laparoscopic method was associated with better perioperative outcomes; the laparoscopy-assisted method is used by surgeons for unique resections such as resection of cirrhotic livers, laparoscopic resection of tumors in unfavorable locations, and living donor hepatectomies. In addition, the laparoscopic major hepatectomy-specific, long-term oncologic outcomes remain to be addressed in future publications.

Laparoscopy-assisted major liver resections employing a hanging technique: the original procedure.

Objective:To assess the feasibility, safety, and short-term outcomes of laparoscopy-assisted major liver resections. Summary of Background Data:The number of reports of laparoscopic major hepatectomies has gradually increased, and living donor hepatectomies for liver transplant have also recently been performed. However, because of the high degree of proficiency required, major hepatectomies have not been widespread. We developed an original procedure in which the liver is mobilized laparoscopically and resected by a hanging technique through a small incision. Methods:Between November 2002 and December 2008, 43 patients underwent laparoscopy-assisted major liver resections (LAMLRs) in our institution for hepatocellular carcinoma, metastatic liver cancer, and benign diseases. Results:LAMLRs were completed for 42 patients (97.7%). The median age was 62 years (range: 24–83 years). Preoperative diagnoses were hepatocellular carcinoma (n = 15), metastatic liver cancer (n = 19), and benign disease (n = 8). The types of liver resection consisted of the following: right trisectionectomy (n = 2), right hepatectomy (n = 14), left hepatectomy (n = 16), trisegmentectomy 4, 5, 8 (n = 2), right anterior sectionectomy (n = 4), and extended right posterior sectionectomy (n = 4). The median operating time was 317 minutes (range: 192–542 minutes) and median blood loss was 631 mL (range: 68–2785 mL). There were neither perioperative deaths nor reoperations. Five patients (11.9%) experienced postoperative complications, 2 patients (4.8%) showed bile leakage, and 3 patients (7.1%) developed wound infections. The median postoperative hospital stay was 13.5 days (range: 6–154 days). Conclusions:LAMLR with the hanging technique can be completed safely. The procedure can be performed by open liver surgeons; and thus may be widely performed in the future.

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase.

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24−/CD44+/ESA+) that were isolated from both ER+ and ER− breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol.