Michael I. D'Angelica

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.

Actual 10-Year Survival After Resection of Colorectal Liver Metastases Defines Cure

PURPOSE Resection of colorectal liver metastases (CLM) in selected patients has evolved as the standard of care during the last 20 years. In the absence of prospective randomized clinical trials, a survival benefit has been deduced relative to historical controls based on actuarial data. There is now sufficient follow-up on a significant number of patients to address the curative intent of resecting CLM. METHODS Retrospective review of a prospectively maintained database was performed on patients who underwent resection of CLM from 1985 to 1994. Postoperative deaths were excluded. Disease-specific survival (DSS) was calculated from the time of hepatectomy using the Kaplan-Meier method. RESULTS There were 612 consecutive patients identified with 10-year follow-up. Median DSS was 44 months. There were 102 actual 10-year survivors. Ninety-nine (97%) of the 102 were disease free at last follow-up. Only one patient experienced a disease-specific death after 10 years of survival. In contrast, 34% of the 5-year survivors suffered a cancer-related death. Previously identified poor prognostic factors found among the 102 actual 10-year survivors included 7% synchronous disease, 36% disease-free interval less than 12 months, 25% bilobar metastases, 50% node-positive primary, 39% more than one metastasis, and 35% tumor size more than 5 cm. CONCLUSION Patients who survive 10 years appear to be cured of their disease, whereas approximately one third of actual 5-year survivors succumb to a cancer-related death. In well-selected patients, there is at least a one in six chance of cure after hepatectomy for CLM. The presence of poor prognostic factors does not preclude the possibility of long-term survival and cure.

Intrahepatic Cholangiocarcinoma : Rising Frequency, Improved Survival, and Determinants of Outcome After Resection

Background:Despite data suggesting a rising worldwide incidence, intrahepatic cholangiocarcinoma (IHC) remains an uncommon disease. This study analyzes changes in IHC frequency, demographics, and treatment outcome in a consecutive and single institutional cohort. Methods:Consecutive patients with confirmed IHC seen and treated over a 16-year period were included. The trend in IHC frequency over the study period was compared with that of hilar cholangiocarcinoma patients (HCCA) seen during the same time. Demographics and patient disposition, histopathologic, treatment, recurrence, and survival data were analyzed; changes in these variables over time were assessed. Results:From December 1990 through July 2006, 594 patients were evaluated (IHC = 270, HCCA = 324). Over the study period, the average annual increase in new IHC patients was 14.2% (P < 0.001). Relative to HCCA, the proportional increase in IHC was nearly 3-fold, and new IHC patients have outnumbered those with HCCA by 2:1 over the last 3 years. Conditions associated with IHC were rarely seen, with only 7 patients having a history of sclerosing cholangitis and/or inflammatory bowel disease and none with hepatolithiasis or biliary parasitic disease; however, heavy tobacco use (27%) and diabetes mellitus (16.4%) were particularly prevalent. The majority of patients were not candidates for resection, most commonly because of advanced hepatic disease. After resection (n = 82), median disease-specific survival was 36 months; recurrence was observed in 62.2% of patients at a median follow-up of 26 months, with the liver remnant involved most frequently (62.7%). Multiple hepatic tumors (P < 0.001), regional nodal involvement (P = 0.012), and large tumor size (P = 0.016) independently predicted poor recurrence-free survival. Most patients (n = 115, 73.7%) with unresectable disease were treated with chemotherapy, either systemic alone (n = 75) or combined with regional hepatic arterial floxuridine (FUDR) (n = 28). Compared with the first 10 years of the study (1990–2000), the last 6 years saw an overall improvement in disease-specific survival for all patients (22 vs. 12 months, P = 0.002), which was particularly notable for patients with unresectable disease (15 vs. 6 months, P = 0.003). Conclusions:At Memorial Sloan-Kettering Cancer Center, IHC incidence has increased dramatically in the last 16 years. Resection offers the best opportunity for long-term survival but is possible in the minority, and patients with large, node-positive or multifocal IHC seem to derive little benefit. Establishing and maintaining control of the intrahepatic disease remains the biggest problem for all IHC patients. The recent increase in survival seems largely because of improved nonoperative therapy for unresectable disease.

Patterns of Initial Recurrence in Completely Resected Gastric Adenocarcinoma

Objective:To review recurrence patterns in completely resected gastric adenocarcinoma. Summary Background Data:Despite improvements in the surgical treatment of gastric adenocarcinoma, recurrence rates remain high in patients with advanced stage disease. Understanding the timing and patterns of recurrence is essential to develop effective adjuvant treatment strategies. Methods:A retrospective review of a prospectively maintained gastric cancer database was carried out. The timing and pattern of recurrence were reviewed. Univariate and multivariate analyses were performed to identify factors predictive of recurrence patterns. Results:From July 1985 through June 2000, 1172 patients underwent an R0 resection. Of these, 496 (42%) had recurrence and complete data on recurrence could be obtained in 367 patients (74%). Among the documented recurrences, 79% were detected within 2 years of operation. Locoregional sites were involved as any part of the recurrence pattern in 199 patients (54%). Distant sites were involved as any part of the recurrence in 188 patients (51%) and peritoneal recurrence was detected as any part of the recurrence in 108 patients (29%). On multivariate analysis, peritoneal recurrence was associated with female gender, advanced T-stage, and distal and diffuse type tumors; locoregional recurrence was associated with male gender and proximal location; distant recurrence was associated with proximal location, early T stage, and intestinal type tumors. The median time to death from the time of recurrence was 6 months. Conclusions:Recurrence after complete resection of gastric adenocarcinoma usually occurs within 2 years and is rapidly fatal. Patterns of recurrence are variable and may be associated with specific clinicopathologic factors.

Impact of steatosis on perioperative outcome following hepatic resection

Fatty liver disease may interfere with liver regeneration and is postulated to result in an adverse outcome for patients subjected to partial hepatectomy. This study examines the impact of steatosis on outcome following hepatic resection for neoplasms. All patients with fatty livers (n = 325) who underwent hepatectomy between December 1991 and September 2001 were identified from a prospective database. Slides were reviewed and steatosis was quantified as follows: <30% (mild) and ≧30% (marked). Patient data were gathered and compared with results in 160 control patients with normal livers; subjects were matched for age, comorbidity, and extent of liver resection. There were 223 patients with mild and 102 with marked steatosis. Those with steatosis were more likely to be men (59% marked vs. 55% mild vs. 43% control; P = 0.01)withahigherbodymassindex(29.7± 5.5 marked vs. 28.2 ± 5.5 mild vs. 26.0 ± 5.4 control; P<0.01), and treated preoperatively with chemotherapy (66% marked vs. 55% mild vs. 38% control; P < 0.01). Total (62%, 48%, and 35%; P< 0.01) and infective (43%, 24%, and 14%; P< 0.01) complications correlated with the degree of steatosis. No difference was observed in complications requiring major medical intervention, hospitalization, or admission to the intensive care unit between groups. On multivariate analysis, steatosis was an independent predictor of complications (P< 0.01, risk ratio = 3.04, 95% confidence interval = 1.7 to 5.54). There was a nonsignificant trend toward higher 60-day mortality in patients with marked steatosis who had lobe or more resections (9.4% marked vs. 5.0% mild vs. 5.0% control; P = 0.30). Marked steatosis is an independent predictor of complications following hepatic resection but does not have a significant impact on 60-day mortality. Steatosis alone should not preclude aggressive hepatic resection for neoplasms when indicated; however, patients with marked steatosis undergoing large resections should still be approached with due caution.

Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection

Liver-enhancing modalities, such as portal vein embolization, are increasingly employed prior to major liver resection to prevent postoperative liver dysfunction. Selection criteria for such techniques are not well described. This study uses CT-based volumetric analysis as a tool to identify patients at highest risk for postoperative hepatic dysfunction. Between July 1999 and December 2000, a total of 126 consecutive patients who were undergoing liver resection for colorectal metastasis and had CT scans at our institution were included in the analysis. Volume of resection was determined by semiautomated contouring of the liver on preoperative volumetrically (helical) acquired CT scans. Hepatic dysfunction was defined as prothrombin time greater than 18 seconds or serum bilirubin level greater than 3 mg/dl. Marginal regression was used to compare the predictive ability of volumetric analysis and the extent of resection. The percentage of liver remaining was closely correlated with increasing prothrombin time and bilirubin level (P < 0.001). After trisegmentectomy, 90% of patients with ≤s25% of liver remaining developed hepatic dysfunction, compared with none of the patients with more than 25% of liver remaining after trisegmentectomy (P < 0.0001). The percentage of liver remaining was more specific in predicting hepatic dysfunction than was the anatomic extent of resection (P = 0.003). Male sex nearly doubled the risk of hepatic dysfunction (odds ratio = 1.89, P = 0.027), and having ≤25% of liver remaining more than tripled the risk (odds ratio = 3.09, P < 0.0001). Hepatic dysfunction and ≤25% of liver remaining were associated with increased complications and length of hospital stay (P < 0.0001 and P = 0.0003, respectively). Preoperative assessment of future liver volume remaining distinguishes which patients undergoing liver resection will most likely benefit from preoperative liver enhancement techniques such as portal vein embolization.

Intraductal Papillary Mucinous Neoplasms of the Pancreas: An Analysis of Clinicopathologic Features and Outcome

Objective:To define the natural history of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas and to identify clinical and pathologic prognostic features. Summary Background Data:IPMN of the pancreas is a recently described pancreatic tumor. Because of a limited number of cases, prognostic factors and the natural history of resected cases have not been well defined. Materials and Methods:A prospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed. Pathologic re-review of each case was performed, and the clinicopathologic features were examined. Log rank and χ2 analysis were used to identify factors predictive of survival and recurrence. Results:Over a 17-year period, 63 patients were identified. One patient was unresectable, 6 (10%) underwent a total pancreatectomy, and 56 (89%) had a partial pancreatectomy. Invasive carcinoma was present in 30 patients (48%). Transection margins were involved with atypia or carcinoma in 32 patients (51%). The median follow-up for survivors was 38 months. Disease-specific 5- and 10-year survival were 75% and 60%, respectively. Significant predictors of poor outcome included presentation with elevated bilirubin, presence of invasive carcinoma, increasing size and percentage of invasive carcinoma, histologic type of invasive carcinoma, positive lymph nodes, and vascular invasion. The presence of atypia or carcinoma in situ at the ductal resection margin was not associated with a poor outcome. Conclusions:Overall, IPMN has a favorable prognosis. Poor outcome in a subset of patients is largely the result of the presence, extent, and type of an invasive component, lymph node metastases, and vascular invasion.

Survival after Hepatic Resection for Metastatic Colorectal Cancer: Trends in Outcomes for 1,600 Patients during Two Decades at a Single Institution

BACKGROUND This study analyzes factors associated with differences in long-term outcomes after hepatic resection for metastatic colorectal cancer over time. STUDY DESIGN Sixteen-hundred consecutive patients undergoing hepatic resection for metastatic colorectal cancer between 1985 and 2004 were analyzed retrospectively. Patients were grouped into 2 eras according to changes in availability of systemic chemotherapy: era I, 1985 to 1998; era II, 1999 to 2004. RESULTS There were 1,037 patients in era I and 563 in era II. Operative mortality decreased from 2.5% in era I to 1% in era II (p = 0.04). There were no differences in age, Clinical Risk Score, or number of hepatic metastases between the 2 groups; however, more recently treated patients (era II) had more lymph node-positive primary tumors, shorter disease-free intervals, more extrahepatic disease, and smaller tumors. Median follow-up was 36 months for all patients and 63 months for survivors. Median and 5-year disease-specific survival (DSS) were better in era II (64 months and 51% versus 43 months and 37%, respectively; p < 0.001); but median and 5-year recurrence-free survival (RFS) for all patients were not different (23 months and 33% era II versus 22 months and 27% era I; p = 0.16). There was no difference in RFS or DSS for high-risk (Clinical Risk Score >2, n = 506) patients in either era. There was a marked improvement in both RFS and DSS for low risk (Clinical Risk Score < or =2, n = 1,094) patients. CONCLUSIONS Despite worse clinical and pathologic characteristics, survival but not recurrence rates after hepatic resection for colorectal metastases have improved over time and might be attributable to improvements in patient selection, operative management, and chemotherapy. The improvement in survival over time is largely accounted for by low-risk patients.

Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.

Current approaches to adjuvant treatment after resection of gallbladder carcinoma (GBCA) and hilar cholangiocarcinoma (HCCA) are based on an incomplete understanding of the recurrence patterns of these diseases. Through an in‐depth analysis of the sites of initial recurrence after resection of GBCA and HCCA, the current study aimed to highlight differences in the biology of these tumors and to provide further insight for adjuvant therapeutic strategies.

Operative Blood Loss Independently Predicts Recurrence and Survival After Resection of Hepatocellular Carcinoma

Objective:To determine if the degree of blood loss during resection of hepatocellular carcinoma (HCC) is predictive of recurrence and long-term survival. Background:Several studies have addressed the impact of blood transfusion on survival and recurrence after liver resection for HCC. However, the independent effect of intraoperative estimated blood loss (EBL) on oncologic outcome is unclear. Methods:From our prospective database, we identified 192 patients who had a partial hepatectomy for HCC from 1985 to 2002. Clinicopathologic predictors of EBL were identified using logistic regression. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were assessed using the Kaplan-Meier and Cox regression methods. Results:The median patient age was 64 (range, 19–86) and 66% were men. All patients had histologically proven HCC. The median follow-up time was 34 months (range, 1–297). Factors associated with increased EBL on multivariate analysis were male gender, vascular invasion, extent of hepatectomy, and operative time (P < 0.01). EBL and vascular invasion were independent predictors of OS and DSS. Only EBL was significantly associated with RFS on multivariate analysis (P = 0.02). Additionally, we found a significant inverse correlation between increasing levels of EBL and length of DSS (P = 0.01). Conclusions:The magnitude of EBL during HCC resection is related to biologic characteristics of the tumor as well as the extent of surgery. Increased intraoperative blood loss during HCC resection is an independent prognostic factor for tumor recurrence and death.