Laurens T. de Wit

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results. METHODS Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group (log-rank, p = 0.737). No reduction of locoregional recurrence rates was apparent in the groups. CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated. However, the benefit in this study was small; routine use of adjuvant chemoradiotherapy is not warranted as standard treatment in cancer of the head of the pancreas or periampullary region.

Rates of Complications and Death After Pancreaticoduodenectomy: Risk Factors and the Impact of Hospital Volume

ObjectiveTo perform a two-part study of pancreaticoduodenectomy in the Netherlands, focusing on the effects of risk factors on outcomes in a single high-volume hospital and the effect of hospital volume on outcomes. Summary Background DataHospital volume and surgeon caseload can be related to the rates of complications and death, and the influence of risk factors can be volume-dependent. Provision of regionalized care should take this into account. MethodsIn part A, a single-institution database on 300 consecutive patients undergoing pancreaticoduodenectomy was divided into two periods with similar numbers of patients. Overall complications, deaths, hospital stay, and risk factors were analyzed in the two periods and compared with an historical reference group. In part B, Netherlands medical registry data on age and postoperative death of patients who underwent partial pancreaticoduodenectomy from 1994 to 1998 were analyzed for the influence of hospital volume on death. ResultsBetween the time periods, the institutional death rate decreased from 4.9% to 0.7%, the complication rate from 60% to 41%. Median hospital stay decreased from 24 to 15 days. The death rate was not related to patient age and did not differ between surgeons. Serum creatinine levels, need for blood transfusion, and period of resection were independent risk factors for complications. The death rate after pancreaticoduodenectomy in the Netherlands was 12.6% in 1994 and 10.1% in 1998; it was greater in patients older than age 65. During the 5-year period, 40% of the procedures were performed in hospitals performing fewer than five resections per year, and the death rate was greater than in hospitals performing more than 25 resections per year. ConclusionsThe overall death rate after pancreaticoduodenectomy did not decrease significantly during the period, and it was greater in low-volume hospitals and older patients. The lower death and complication rates in high-volume hospitals, including the single-center outcomes, were similar to those reported in other countries and may be due to better prevention and management of complications. Pancreaticoduodenectomy should be performed in centers with sufficient experience and resources for support.

Incidence, risk factors, and treatment of pancreatic leakage after pancreaticoduodenectomy: drainage versus resection of the pancreatic remnant.

BACKGROUND Pancreatic leakage is a major cause of morbidity and mortality after pancreaticoduodenectomy, with incidences varying between 6-24% and a mortality rate up to 40%. Treatment is an issue of controversy. In this study we analyzed risk factors for pancreatic leakage and the results of early resection of the pancreatic remnant versus drainage procedures for leakage of the pancreaticojejunostomy. STUDY DESIGN From 1983 to 1995, 269 patients underwent pancreaticoduodenectomy, with pancreaticojejunostomy. Patients with manifestations of pancreatic leakage were compared with nonleakage patients to evaluate risk factors. Patients with leakage were divided into two treatment groups. One group comprised patients undergoing percutaneous or surgical drainage procedures; the other had patients undergoing resection of the pancreatic remnant. RESULTS Twenty-nine patients (11%) had clinical manifestations of pancreatic leakage, and the mortality in these patients was 28% (overall mortality: 3.7%). Leakage occurred after a median of 5 days (range 1-20). Age, preoperative bilirubin level, and albumin counts were not risk factors for pancreatic leakage. Small pancreatic duct size (< 2 mm) (p < 0.01) and ampullary carcinoma as histopathologic diagnosis (p < 0.05) were risk factors. The median number of relaparotomies was two (range 0-4) in the drainage group (n = 21), versus 1.5 (range 1-5) in patients who underwent resection (n = 8). The median hospital stay was 74 days (range 36-219), versus 55 days (range 22-107) for the drainage and resection groups, respectively (p < 0.05). Mortality was lower in patients who underwent resection, 38 versus 0% (p < 0.05). CONCLUSIONS Leakage of the pancreatic anastomosis is a severe complication after pancreaticoduodenectomy and carries a high mortality rate (28%). Completion pancreatectomy could be performed without additional mortality. In patients with severe and persistent leakage of the anastomosis, early completion pancreatectomy is the treatment of choice.

Results of pancreaticoduodenectomy for ampullary carcinoma and analysis of prognostic factors for survival

BACKGROUND Results of pancreaticoduodenectomy for ampullary carcinoma were evaluated, and prognostic factors for survival were analyzed. METHODS During the period from 1984 to 1992 67 patients underwent subtotal or total pancreaticoduodenectomy for ampullary carcinoma. All clinicopathologic data and their influence on survival were studied. RESULTS Subtotal pancreaticoduodenectomy was performed in 62 of 67 patients with a mortality of 6% and a morbidity of 65%; the remaining five patients underwent total pancreaticoduodenectomy. Intraabdominal infection was the most important complication. Resection margins were tumor free in 75% of 67 patients. The overall 5-year survival was 50%. Survival was significantly influenced by the involvement of resection margins. After resection with involved margins 5-year survival was 15% and 60% after resection with free margins (p < 0.001). Tumor size, lymph node involvement, and differentiation grade had limited and not significant influence on survival. CONCLUSIONS Subtotal pancreaticoduodenectomy is the type of resection of first choice for ampullary carcinoma. Involvement of resection margins was the strongest prognostic factor for survival. Patients with a tumor size larger than 2 cm, with lymph node involvement, or with a poorly differentiated tumor still had a 5-year survival rate greater than 40%. Patients with involved margins might be candidates for studies on adjuvant therapy.

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BackgroundRecent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay.The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease.Methods/designThe LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate.Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected.DiscussionThe LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease.

Staging laparoscopy and laparoscopic ultrasonography in more than 400 patients with upper gastrointestinal carcinoma

BACKGROUND Resection offers the only chance of cure to patients with esophageal, gastroesophageal junction, and hepatopancreatobiliary tumors. Staging is essential to select patients who will benefit from operation because palliation can also be performed nonoperatively. Several studies, including limited numbers of patients, have shown that laparoscopic staging prevents unnecessary laparotomies, but it is doubtful whether general application of this staging method can be advised. The aim of this study was to assess the benefit of diagnostic laparoscopy for staging patients with esophageal, gastroesophageal junction, and hepatopancreatobiliary tumors. STUDY DESIGN Between June 1992 and December 1996, 420 patients with a resectable tumor after conventional staging underwent diagnostic laparoscopy combined with laparoscopic ultrasonography. Histologic proof of metastases or ingrowth was used to cancel laparotomy. RESULTS Laparoscopic staging avoided laparotomy in 20% of patients (sensitivity 0.70): 5% with an esophageal tumor, 20% with a gastroesophageal junction tumor, 15% with a periampullary tumor, 40% with a proximal bile duct tumor, 35% with a liver tumor, and 40% with a pancreatic body or tail tumor. Complications and port-site metastases were seen in 4% and 2% of patients, respectively. CONCLUSIONS Laparoscopic staging is a safe procedure with low morbidity and without mortality in this series. It has shown no benefit in esophageal cancer, but seems beneficial for staging tumors located at the gastroesophageal junction, proximal bile duct tumors, liver tumors, and pancreatic body and tail tumors. The value of laparoscopic staging for patients with periampullary tumors is not as great as stated in previous studies and is still the subject of investigation.

Palliative treatment in patients with unresectable hilar cholangiocarcinoma: results of endoscopic drainage in patients with type III and IV hilar cholangiocarcinoma.

OBJECTIVE To find out how patients fared after palliative endoscopic biliary drainage for inoperable hilar cholangiocarcinoma. DESIGN Retrospective study. SETTING University hospital, the Netherlands. SUBJECTS Between 1992 and 1999, 41 patients who were referred for resection had tumours that were considered unresectable after additional investigations, including an exploratory laparotomy in 16 patients. In all patients, biliary drainage was established by endoscopic retrograde cholangiography (ERCP) and insertion of endoprostheses. Twelve patients also had percutaneous transhepatic biliary drainage (PTBD). RESULTS The patients who did not have an exploratory laparotomy had fewer complications (1/25) than those who had explorations (4/16). All patients in both groups had one or more long-term complications during follow-up, of which cholangitis, jaundice, and abdominal pain were the most often recorded. In 32 patients, endoprostheses had to be replaced, a mean of 4 times. Median survival was 9 months, with no significant difference between the groups (8 and 11 months). Adjuvant radiotherapy had no influence on survival. CONCLUSION The patients in this series had relatively long survival times, during which they had a substantial number of complications predominantly related to biliary drainage. Because biliary-enteric bypass operations result in effective relief of symptoms and excellent palliation, we suggest that when an exploration is done for patients with type III and IV tumours, a bypass should be made.

Two Patients with Chronic Pancreatitis Complicated by a Pancreaticopleural Fistula

Two patients presented with dyspnea and signs of chronic pancreatitis. Patient B had pleural effusion on chest X-ray. Patient A developed pleural effusion during the course of disease. On further analysis these pleural effusions showed elevated amylase concentrations. This finding suggested the diagnosis of a pancreaticopleural fistula which was confirmed by magnetic resonance cholangiopancreatography. Because of the distinct localization of the fistulas the patients were treated differently. In patient A an endoprosthesis was successfully placed in the pancreatic duct, and patient B underwent distal pancreatic resection. Considering the rarity of pancreaticopleural fistula, there is no consensus on diverse aspects of treatment, such as length of treatment with octreotide. However, a rationale for the distinction between fistulas suited for treatment with endoprosthesis or surgery seems to provide some grip.