Anthony T. Ruys

Extent of liver resection for hilar cholangiocarcinoma (Klatskin tumor): how much is enough?

Background: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. Methods: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. Results: The majority of resections (78%) were performed for Bismuth type III–IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. Conclusion: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%.

Jejunal cancer in patients with familial adenomatous polyposis.

BACKGROUND & AIMS Familial adenomatous polyposis (FAP) is an inherited disease affecting approximately 1:10,000 newborns, characterized by the formation of numerous adenomas in the digestive tract. Surveillance and prophylactic treatment of colonic and duodenal manifestations of this disease have much influenced disease course and survival. In more recent years, it has become clear that adenoma formation in FAP patients is not restricted to the colon and duodenum. Accordingly, these adenomas might have malignant potential, although the actual risk is unknown. METHODS We report 3 cases of jejunal carcinoma in FAP patients and review data on incidence, prognosis, and risk factors of jejunoileal adenoma and carcinoma development in FAP. RESULTS Three patients with FAP aged 71, 57, and 59 years developed advanced duodenal adenomatosis and a jejunal carcinoma, which was associated with poor prognosis in 2 patients. CONCLUSIONS Jejunal adenomas in FAP patients are reported occasionally and can progress into adenocarcinoma with a poor prognosis. In the future a subset of FAP patients benefitting from jejunal surveillance should be identified.

FDG-positron emission tomography/computed tomography and standardized uptake value in the primary diagnosis and staging of hilar cholangiocarcinoma.

BACKGROUND The diagnosis and staging of hilar cholangiocarcinoma (HCCA) remain challenging despite recent advances in imaging. Little is known about the use of positron emission tomography/computed tomography (PET/CT) in HCCA. OBJECTIVES This study aimed to evaluate the additional value of FDG-PET/CT and standardized uptake value (SUV) in patients with highly suspected HCCA. METHODS Between February 2006 and August 2009, PET/CT was performed in 30 patients with highly suspected HCCA, all of whom were deemed resectable by conventional staging methods, including laparoscopy. The results of PET-CT and SUV were compared with intraoperative and histopathological findings. RESULTS The primary tumour was (18) F-FDG-positive in 88% of patients. Sensitivity and specificity for the detection of regional lymph node metastases and distant metastases were 67% and 68%, and 33% and 96%, respectively. The median SUV in the primary tumour was significantly (P < 0.05) higher in patients with (mean: 8.9) than without (mean: 6.1) distant metastases. The SUV in patients with benign disease (n= 4) showed a trend towards lower values than in patients with cholangiocarcinoma, although this was not significant. CONCLUSIONS After conventional staging including diagnostic laparoscopy, the additional value of PET/CT is limited. This somewhat disappointing finding may reflect the fact that extensive staging studies were carried out prior to PET/CT. The SUV potentially predicts patients with distant metastases and may differentiate between HCCA and benign lesions that mimic malignancies.

Differences in immunohistochemical biomarkers between intra- and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis

Cholangiocarcinomas of different locations differ in growth patterns, symptoms, treatment response, and survival. Still, they are regarded in many studies as a uniform malignancy. Because intra‐ (iCCA) and extrahepatic (eCCA) cholangiocarcinoma display such differences, we performed a systematic review and meta‐analysis to analyze differences in the immunohistochemical profile of these tumors.

Metastatic lymph nodes in hilar cholangiocarcinoma: does size matter?

AIM To determine the diagnostic efficacy of the size criteria for the detection of metastatic lymph nodes (LN) in patients with hilar cholangiocarcinoma (HCCA). INTRODUCTION LN metastasis is one of the most significant independent prognostic factors in patients with HCCA. Presently, in spite of the well known lack of sensitivity and specificity, one of the most used clinical criteria for nodal metastases is LN size. METHODS Pathological slides of 147 patients who had undergone exploration for HCCA were assessed. The size (maximum and short axis diameter) of each single node was retrieved from the pathology report or measured from a section on the glass slide using a stereo microscope and a calibrated ruler integrated in the software. When a metastatic lesion was detected, the proportion of the lesion in relation to LN size was estimated. RESULTS Out of 147 patients, 645 LN were retrieved and measured. In all, 106 nodes (16%) showed evidence of metastasis. The proportion of positive nodes was 8% in nodes <5 mm and 37% in nodes >30 mm. Ten per cent of LN smaller than 10 mm were positive, whereas only 23% of LN larger than 10 mm were metastastically involved. No clear cut-off point could be found. Similar results were found for the short axis diameter. In 50% of positive LN, the metastatic lesion accounted for 10% or less of the LN size. CONCLUSION No cut-off point could be determined for accurately predicting nodal involvement. Therefore, imaging studies should not rely on LN size when assessing nodal involvement.

Prognostic Impact of Preoperative Imaging Parameters on Resectability of Hilar Cholangiocarcinoma

Objectives. To evaluate, in hilar cholangiocarcinoma (HCCA), the prognostic impact of specific preoperative radiologic parameters on resectability, metastases, and yield of laparoscopy, and to evaluate the currently used staging systems. Methods. Consecutive patients with HCCA presenting in our center from January 2003 through August 2010 were evaluated. Suspicion on lymph node metastasis, portal vein and hepatic artery involvement, lobar atrophy, and proximal extent of ductal invasion was scored. The prognostic value of these parameters for predicting resectability, yield of diagnostic laparoscopy, likelihood of metastatic disease, R0 resection, and survival was assessed. The Bismuth-Corlette classification and MSKCC staging system were evaluated. Results. Of all 289 evaluated patients, 158 patients (55%) had unresectable disease based on cross-sectional imaging studies or diagnostic laparoscopy; 131 patients (45%) underwent exploration. 83 patients (64%) underwent resection, of whom 67 (87%) had a radical (R0) resection. Suspicious lymph nodes and involvement of the hepatic artery were important prognostic factors for resectability. Predictive power of the evaluated staging systems was limited. Conclusions. Current staging systems predict resectability, but there is room for improvement. Hepatic artery involvement and nodal status might be important factors for prediction of resectability and should be considered in future staging systems.

Effects of Prolonged Pneumoperitoneum on Hepatic Perfusion During Laparoscopy

Objective: To assess the influence of prolonged pneumoperitoneum (PP) on liver function and perfusion in a clinically relevant porcine model of laparoscopic abdominal insufflation. Background: PP during laparoscopic surgery produces increased intra-abdominal pressure, which potentially influences hepatic function and microcirculatory perfusion. Methods: Six pigs (49.6 ± 5.8 kg) underwent laparoscopic intra-abdominal insufflation with 14 mm Hg CO2 gas for 6 hours, followed by a recovery period of 6 hours. Two animals were subjected to 25 mm Hg CO2 gas. Hemodynamic parameters were monitored, and damage parameters in the blood were measured to assess liver injury. Liver total blood flow and function were determined by the indocyanine green (ICG) clearance test. Intraoperative hepatic hemodynamics were measured by simultaneous reflectance spectrophotometry (venous oxygen saturation StO2 and relative tissue hemoglobin concentration rHb) and laser Doppler flowmetry (blood flow and flow velocity). Postmortem liver samples were collected for histological evaluation. Results: A decrease in microvascular perfusion was observed during PP. After 6 hours of PP, ICG clearance increased (P < 0.001), indicating a compensatory improvement of overall liver blood flow resulting in concomitantly improved microcirculatory perfusion (P = 0.024). Minimal parenchymal damage (aspartate aminotransferase) of the liver was seen after 6 hours of PP (P = 0.006), which seemed related to PP pressure. Minor histological damage was observed. Conclusions: The liver sustains no additional damage due to prolonged PP during laparoscopic surgery. Our findings suggest that prolonged PP does not hamper liver function or cause liver damage after extended laparoscopic procedures.

Delay in surgical treatment of patients with hilar cholangiocarcinoma: does time impact outcomes?

BACKGROUND Substantial time elapses before patients with hilar cholangiocarcinoma (HCC) receive surgical treatment because of time-consuming preoperative staging and other interventions, including biliary drainage and portal vein embolization. Prolonged times potentially lead to unresectability and the formation of metastases, yet these issues have not been investigated previously in HCC. This study aimed to evaluate the time between onset of symptoms and the provision of ultimate treatment in patients with HCC and the impact of the length of time on outcomes. METHODS Delays in the treatment of consecutive patients with HCC were evaluated by contacting general practitioners (GPs) and extracting data from hospital files. Time periods were correlated with resectability, occurrence of metastasis, tumour stage and survival using logistic and Cox regression analyses. RESULTS Treatment times in 209 consecutive HCC patients were evaluated. The median time from first GP visit until presentation at the tertiary centre was 35 days. Time until treatment was longer when initial symptoms did not include jaundice (non-specific symptoms, P < 0.001). Duration of workup and preoperative biliary drainage at the tertiary centre prior to final surgical treatment resulted in an additional median time of 74 days. No correlation was found between treatment time in weeks and resectability [odds ratio (OR) 1.010, 95% confidence interval (CI) 0.985-1.036], metastasis (OR = 0.947, 95% CI 0.897-1.000), tumour stage (OR = 1.006, 95% CI 0.981-1.031) or survival in resected patients (hazard ratio = 0.996, 95% CI 0.975-1.018). CONCLUSIONS The time that elapses between the presentation of symptoms and final treatment in patients with HCC is substantial, especially in patients with non-specific symptoms. This time, however, does not affect resectability, metastasis, tumour stage or survival, which suggests that preoperative optimization should not be omitted because of potential delays in treatment.

Erratum to: Surgical Treatment of Renal Cell Cancer Liver Metastases: A Population-Based Study

The online version of the original article can be found under doi:10.1245/s10434-010-1526-x.

Erratum to: Surgical Treatment of Renal Cell Cancer Liver Metastases: A Population-Based Study (vol 18, pg 1932, 2011)

The online version of the original article can be found under doi:10.1245/s10434-010-1526-x.