Robbert J. de Haas

R1 Resection by Necessity for Colorectal Liver Metastases Is It Still a Contraindication to Surgery

Objective:To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery. Summary Background Data:Complete macroscopic resection with negative margins is the gold standard recommendation in the surgical treatment of CLM. However, due to vascular proximity or multinodularity, complete macroscopic resection can sometimes only be performed through R1 resection. Increasingly efficient chemotherapy may have changed long-term outcome after R1 resection. Methods:All resected CLM patients (R0 or R1) at our institution between 1990 and 2006 were prospectively evaluated. Exclusion criteria were: macroscopic incomplete (R2) resection, use of local treatment modalities, and presence of extrahepatic disease. We aimed to resect all identified metastases with negative margins. However, when safe margins could not be obtained, resection was still performed provided complete macroscopic tumor removal. Overall survival (OS) and disease-free survival were compared between groups, and prognostic factors were identified. Results:Of 840 patients, 436 (52%) were eligible for the study, 234 (28%) of whom underwent R0 resection, and 202 (24%) underwent R1 resection. Number and size of CLM were higher, and distribution was more often bilateral in the R1 group. After a mean follow-up of 40 months, 5-year OS was 61% and 57% for R0 and R1 patients (P = 0.27). Five-year disease-free survival was 29% in the R0 group versus 20% in the R1 group (P = 0.12). In the R1 group, intrahepatic (but not surgical margin) recurrences were more often observed (28% vs. 17%; P = 0.004). Preoperative carcinoembryonic antigen level ≥10 ng/mL and major hepatectomy, but not R1 resection, were independent predictors of poor OS. Size ≥30 mm, bilateral distribution, and intraoperative blood transfusions independently predicted positive surgical margins. Conclusions:Despite a higher recurrence rate, the contraindication of R1 resection should be revisited in the current era of effective chemotherapy because survival is similar to that of R0 resection.

Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases.

Objective:To assess feasibility, risks, and long-term outcome of 2-stage hepatectomy as a means to improve resectability of colorectal liver metastases (CLM). Summary Background Data:Two-stage hepatectomy uses compensatory liver regeneration after a first noncurative hepatectomy to enable a second curative resection. Methods:Between October 1992 and January 2007, among 262 patients with initially irresectable CLM, 59 patients (23%) were planned for 2-stage hepatectomy. Patients were eligible when single resection could not achieve complete treatment, even in combination with chemotherapy, portal embolization, or radiofrequency, but tumors could be totally removed by 2 sequential resections. Feasibility and outcomes were prospectively evaluated. Results:Two-stage hepatectomy was feasible in 41 of 59 patients (69%). Eighteen patients failed to complete the second hepatectomy because of disease progression (n = 17) or bad performance status (n = 1). The 41 successfully treated patients had a mean number of 9.1 metastases (mean diameter, 48.5 mm at diagnosis). Chemotherapy was delivered before (95%), in between (78%), and after (78%) the 2 hepatectomies. Mean delay between the 2 liver resections was 4.2 months. Postoperative mortality was 0% and 7% (3/41) after the first and second hepatectomy, respectively. Morbidity rates were also higher after the second procedure (59% vs. 20%) (P < 0.001). Five-year survival was 31% on an intention to treat basis, and all but 2 patients who did not complete the 2-stage strategy died within 19 months. After a median follow-up of 24.4 months (range, 3.7–130.3), overall 3- and 5-year survivals for patients that completed both hepatectomies were 60% and 42%, respectively, after the first hepatectomy (median survival, 42 months from first hepatectomy and 57 months from metastases diagnosis). Disease-free survivals were 26% and 13% at 3 and 5 years, respectively. Conclusions:Two-stage hepatectomy provides a 5-year survival of 42% and a hope of long-term survival for selected patients with extensive bilobar CLM, irresectable by any other means.

Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection.

Background:An expansion of resectability criteria of colorectal liver metastases (CLM) is justified provided “acceptable” short-term and long-term outcomes. The aim of the present study was to ascertain this paradigm in an era of modern liver surgery. Methods:All consecutive patients who underwent hepatic resection for CLM at our institute between 1990 and 2010 were included in the study. Ninety-day mortality and morbidity rates were determined in the total study population and in 2 separate time periods (group I: 1990–2000; group II: 2000–2010). Similarly, overall and progression-free survival rates were determined. Independent predictors of postoperative morbidity were identified at multivariate analysis. Results:Between 1990 and 2010, 1394 hepatectomies were performed in 1028 patients. Overall perioperative mortality and postoperative morbidity rates were 1.3% and 33%, respectively. Although patients in group II were older, had more often comorbid illnesses, and presented with more extensive liver disease, similar perioperative mortality rates were observed (1.1% in group I and 1.4% in group II; P = 0.53). A trend toward a higher morbidity rate was observed in group II (34% vs 31% in group I; P = 0.16). Independent predictors of postoperative morbidity were: treatment between 2000 and 2010, total hepatic ischemia time of 60 minutes or more, maximum size of CLM of 30 mm or more at histopathology, and presence of abnormalities in the nontumoral liver parenchyma. Although a trend toward lower overall survival was observed in patients with significant postoperative complications, no significant differences were observed in long-term outcomes between both treatment periods. Conclusion:After an aggressive multidisciplinary treatment of CLM, acceptable overall mortality and morbidity rates were observed. Perioperative mortality rates did not differ according to treatment period; however, more recently operated patients experienced more postoperative complications. These favorable short-term outcomes, without worsening of long-term outcomes, justify an expansion of the criteria for resectability in this patient category.

Resection of Colorectal Liver Metastases with Extrahepatic Disease

Extrahepatic disease in combination with colorectal liver metastases has long been considered an absolute contraindication for surgery. However, in many reported series, long-term survival is achieved in selected patients with concomitant extrahepatic disease as long as the resection of all metastatic sites is complete. Owing to these results, an increasing number of patients with advanced metastatic colorectal disease are now being referred for surgery. For patients with concomitant liver and lung metastases, sequential resection of both disease sites has proven to be safe, offering a 5-year survival rate of more than 30%. On the contrary, hepatectomy combined with resection of regional lymph node metastases can only provide long-term survival in case of pedicular lymph node involvement. Furthermore, control of the disease by preoperative chemotherapy appears to be crucial. For peritoneal carcinomatosis, aggressive treatment combining cytoreductive surgery and intraperitoneal chemotherapy can offer a chance of prolonged long-term survival to selected patients with limited peritoneal extension. In conclusion, resection of both intra- and extrahepatic colorectal metastases should be considered if resection of all metastatic sites can be complete and the disease is controlled by chemotherapy. Long-term survival in these patients with advanced disease could be achieved if they are managed by experienced multidisciplinary teams.

Glycogen storage disease type Ia adult presentation with microcytic anemia and liver adenomas

Glycogen storage disease type Ia (GSD Ia; OMIM #232200) is an ultra-rare inherited metabolic disorder caused by deficient glucose-6-phosphatase (G6Pase; EC 3.1.3.9) activity, which hydrolyzes glucose-6-phosphate (G6P), to produce glucose in the endoplasmic reticulum lumen in the final common pathway of glycogenolysis and gluconeogenesis. Classically, symptoms and signs in the first year of life include severe fasting intolerance, failure to thrive, and hepatomegaly, biochemically characterized by nonketotic hypoglycemia, fasting hyperlactidemia, hyperuricaemia, and hyperlipidaemia (Fig. 1), but few milder phenotypes are described. Dietary management is the cornerstone of treatment aiming at maintenance of euglycemia, prevention of secondary metabolic perturbations, and long-term complications including the liver (hepatocellular adenomas and carcinomas).

Contents Vol. 25, 2008

N. Ando, Chiba C.G.M.I. Baeten, Maastricht C. Bassi, Verona H.-P. Bruch, Lübeck X.P. Chen, Wuhan S.-T. Fan, Hong Kong A. Fingerhut, Poissy S. Galandiuk, Louisville, Ky. H.G. Gooszen, Utrecht T.M. van Gulik, Amsterdam J.G. Hunter, Portland, Oreg. I. Ihse, Lund J.R. Izbicki, Hamburg J.F. Ji, Beijing M. Kaminishi, Tokyo M.R.B. Keighley, Birmingham J.-P. Kim, Seoul J.J.B. van Lanschot, Rotterdam R.S. Leicester, London H. Lippert, Magdeburg P. Malfertheiner, Magdeburg P.E. O’Brien, Prahran R. Padbury, Adelaide H.A. Pitt, Indianapolis, Ind. L.F. Rikkers, Madison, Wisc. F. Seow-Choen, Singapore J.R. Siewert, Munich M. Sunamura, Sendai Y. Tekant, Istanbul H.W. Tilanus, Rotterdam J. Toouli, Adelaide B. Vollmar, Rostock A.L. Warshaw, Boston, Mass. Official Journal of European Digestive Surgery (EDS)