Busch, O.R.C.

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis (Article)

2011-11-01T00:00:00Z

Background & Aims: A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Methods: Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. Results: During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. Conclusions: In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.

Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer (Article)

2011-02-01T00:00:00Z

Background and purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. Material and methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 × 2.5 Gy radiotherapy combined with UFT 300 mg/m2 per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer (Article)

2011-01-01T00:00:00Z

Background: Neoadjuvant chemoradiotherapy before surgery can improve survival in patients with potentially curable esophageal cancer, but not all patients respond. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed to identify nonresponders early during neoadjuvant chemoradiotherapy. The aim of the present study was to determine whether FDG-PET could differentiate between responding and nonresponding esophageal tumors early in the course of neoadjuvant chemoradiotherapy. Methods: This clinical trial comprised serial FDG-PET before and 14 days after start of chemoradiotherapy in patients with potentially curable esophageal carcinoma. Histopathologic responders were defined as patients with no or less than 10% viable tumor cells (Mandard score on resection specimen). PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic analysis was used to evaluate the ability of SUV in distinguishing between histopathologic responders and nonresponders. Results: In 100 included patients, 64 were histopathologic responders. The median SUV decrease 14 days after the start of therapy was 30.9% for histopathologic responders and 1.7% for nonresponders (P = 0.001). In receiver operating characteristic analysis, the area under the curve was 0.71 (95% CI = 0.60-0.82). Using a 0% SUV decrease cutoff value, PET correctly identified 58 of 64 responders (sensitivity 91%) and 18 of 36 nonresponders (specificity 50%). The corresponding positive and negative predictive values were 76% and 75%, respectively. Background: SUV decrease 14 days after the start of chemoradiotherapy was significantly associated with histopathologic tumor response, but its accuracy in detecting nonresponders was too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer.

Lymphatic micrometastases in patients with early esophageal adenocarcinoma (Article)

2010-12-01T00:00:00Z

Background: Both endoscopic and surgical treatments are recommended for m3- or sm1-adenocarcinomas of the esophagus, depending on patients' lymph nodal status. Lymphatic dissemination is related to tumor infiltration depth, but varying incidences have been reported in m3- and sm1-adenocarcinomas. The study aim was to investigate whether the presence of occult tumor cells in lymph nodes could explain this variation. Methods Sixty-three node-negative (N0) patients with early esophageal adenocarcinoma (m2/m3/sm1-tumors) were included. Multilevel-sectioning of lymph nodes was performed; sections were stained by means of immunohistochemistry with cytokeratin marker CAM5.2. Two pathologists searched for micrometastases (0.2-2.0 mm) and isolated tumor cells (ITCs, <0.2 mm). Results Positive CAM5.2 staining in lymph nodes was not seen in any of the 18 m2-patients. In 2/25 m3-tumors (8.0%) an ITC was found, but no micrometastases. Tumor cells were identified in 4/20 sm1-tumors (20.0%): three micrometastases and one ITC. Median follow-up was 121 months. Two m3-patients (3.2%) died due to disease recurrence, including one patient in whom an ITC was detected. Conclusions Lymphatic migration of tumor cells was found in node-negative m3- and sm1-adenocarcinomas of the esophagus (8.0% and 20.0%, respectively). However, the clinical relevance of these occult tumor cells should become apparent from large series of endoscopically treated patients.

Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage (Article)

2010-11-01T00:00:00Z

Objective: To evaluate the relation between delay in surgery because of preoperative biliary drainage (PBD) and survival in patients scheduled for surgery for pancreatic head cancer. Background: Patients with obstructive jaundice due to pancreatic head cancer can undergo PBD. The associated delay of surgery can lead to more advanced cancer stages at surgical exploration, affecting resection rate and survival. Methods: We conducted a multicenter, randomized controlled clinical trial to compare PBD with early surgery (ES) for pancreatic head cancer for complications. We obtained Kaplan-Meier estimates of overall survival for patients with pathology-proven malignancy and compared survival functions of ES and PBD groups using log-rank test statistics. Multivariable Cox regression analyses were performed to evaluate the prognostic role of time to surgery for overall survival. Results: Mean times from randomization to surgery were 1.2 (0.9-1.5) and 5.1 (4.8-5.5) weeks in the ES and PBD groups, respectively (P < 0.001). In the ES group, 60 (67%) of 89 patients underwent resection, versus 53 (58%) of 91 patients in the PBD group (P = 0.20). Median survival after randomization was 12.2 (9.1-15.4) months in the ES group versus 12.7 (8.9-16.6) months in the PBD group (P = 0.91). A longer time to surgery was significantly associated with slightly lower mortality rate after surgery (hazard ratio = 0.90, 95% CI, 0.83-0.97), when taking into account resection, bilirubin, complications, pancreatic adenocarcinoma, tumor-positive lymph nodes, and microscopically residual disease. Conclusions: In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate. Copyright

Intrathoracic manifestations of cervical anastomotic leaks after transhiatal and transthoracic oesophagectomy (Article)

2010-05-01T00:00:00Z

Background: A possible advantage of cervical oesophagogastrostomy over intrathoracic anastomosis after oesophagectomy is the presumed mild clinical course of cervical anastomotic leakage. The incidence and consequences of intrathoracic manifestations after cervical anastomotic leakage remain unclear, and were investigated in this study. Methods: Consecutive patients undergoing potentially curative transhiatal oesophagectomy (THO) or transthoracic oesophagectomy (TTO) with cervical oesophagogastrostomy between 1993 and 2007 were included. Intrathoracic manifestations after cervical anastomotic leakage were compared following THO and TTO. Multivariable logistic regression analysis was used to identify potential risk factors for intrathoracic manifestations. Results: Seventy-nine (15-8 per cent) of 501 patients developed anastomotic leakage after THO compared with 50 (15.3 per cent) of 327 after TTO (P = 0.853). Intrathoracic manifestations developed in 21 (27 per cent) and 22 (44 per cent) patients respectively (P = 0.041). A transthoracic approach was the only independent predictor of the development of intrathoracic manifestations in patients with cervical leakage (odds ratio 2.60; P = 0.022). Total hospital stay (P < 0.001), intensive care unit stay (P < 0.001) and in-hospital mortality (P = 0.035) were greater in patients with intrathoracic manifestations than in those without. Conclusion: Intrathoracic manifestations of cervical anastomotic leakage are associated with a prolonged hospital stay, carry a higher mortality and occur more frequently after TTO than THO. Copyright

Preoperative biliary drainage for cancer of the head of the pancreas (Article)

2010-01-14T00:00:00Z

BACKGROUND: The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear. METHODS: In this multicenter, randomized trial, we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head. Patients with obstructive jaundice and a bilirubin level of 40 to 250 μmol per liter (2.3 to 14.6 mg per deciliter) were randomly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retrograde cholangiopancreatography. The primary outcome was the rate of serious complications within 120 days after randomization. RESULTS: We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage; 6 patients were excluded from the analysis. The rates of serious complications were 39% (37 patients) in the early-surgery group and 74% (75 patients) in the biliary-drainage group (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P = 0.14). Mortality and the length of hospital stay did not differ significantly between the two groups. CONCLUSIONS: Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.) Copyright

Preoperative and Early Postoperative Quality of Life Predict Survival in Potentially Curable Patients with Esophageal Cancer (Article)

2009-01-01T00:00:00Z

Background: In patients with esophageal cancer, evidence for prognostic significance of preoperative quality of life (QoL) is limited, while the prognostic significance of postoperative QoL has not been investigated at all. Aim: To determine whether preoperative and postoperative QoL measurements can predict survival independently from clinical and pathological factors, in patients with potentially curable esophageal adenocarcinoma. Methods: A randomized controlled trial was performed from 1994 to 2000 in two academic medical centres, comparing transthoracic and transhiatal esophagectomy. QoL questionnaires were sent before and 3 months after surgery (Medical Outcome Study Short Form-20 and Rotterdam Symptom Checklist). Uni- and multivariate Cox regression analyses were used to examine firstly the prognostic value of preoperative QoL and several clinical factors, and secondly of postoperative QoL, several clinical factors, and pathological staging. Results: Out of 220 randomized patients, 199 participated in the QoL-study. In the multivariate preoperative model physical symptom scale (p = 0.021), tumor length (p = 0.034), and endosonographic T-stage (p = 0.003) were predictive for overall survival. In the postoperative multivariate analysis, social functioning (p = 0.035), pain (p = 0.026), and activity level (p = 0.037) predicted survival, besides pathological T-stage (p < 0.001) and N-stage (p < 0.001). Conclusion: In the present paper the first large consecutive series of potentially curable esophageal cancer patients is presented in whom prospectively collected QoL data before and after potentially curative surgical resection were used to predict survival. Both preoperative (physical symptoms) and postoperative (social functioning, pain, and activity level) QoL subscales are independent predictors of survival in potentially curable patients with esophageal adenocarcinoma.

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS) (Article)

2008-12-01T00:00:00Z

Background. A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. Methods/design. The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm. The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. Discussion. This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. Trial registration. ISRCTN80832026.

Pancreas-preserving total duodenectomy versus standard pancreatoduodenectomy for patients with familial adenomatous polyposis and polyps in the duodenum (Article)

2008-11-01T00:00:00Z

Background: Pancreas-preserving total duodenectomy (PPTD) was introduced as a replacement for pancreatoduodenectomy (PD) for familial adenomatous polyposis (FAP). This study analysed the results of PPTD in the Netherlands and reviewed the relevant literature. Methods: All 26 patients who underwent PPTD for FAP in four centres in the Netherlands between January 2000 and January 2007 were compared with a group of 77 patients who had PD for ampulla of Vater adenocarcinoma at one centre during the same interval. Results: Morbidity rates were similar after PPTD for FAP (16 patients, 62 per cent) and PD for ampulla of Vater adenocarcinoma (44 patients, 57 per cent) (P = 0.694). One patient (4 per cent) died after PPTD and two (3 per cent) after PD. A review of the literature, including patients from the present study, found that 71 patients had PPTD, with postoperative morbidity in 36 (51 per cent) and one death (1 per cent). In publications containing a total of 94 patients who underwent PD for FAP, 43 (46 per cent) developed complications and three (3 per cent) died. Conclusion: PPTD has similar short-term results to PD in terms of morbidity and mortality. Copyright

Postoperative complications after esophagectomy for adenocarcinoma of the esophagus are related to timing of death due to recurrence (Article)

2008-01-01T00:00:00Z

BACKGROUND: Esophagectomy is frequently accompanied by substantial complications with secondary disturbance of the immune system. After esophagectomy for adenocarcinoma of the distal esophagus and/or gastroesophageal junction, the majority of patients develops an early recurrence and dies within 2 years. The aim of this study was to determine the relevance of perioperative complications on the timing of death due to recurrence. METHODS: A consecutive series of 351 patients who underwent esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction was reviewed. RESULTS: Of the 351 included patients, 191 patients (54%) died due to recurrence of esophageal adenocarcinoma. Of these 191 patients, 77 (40%), 138 (72%), and 186 patients (97%) died before 12, 24, and 60 months, respectively. Multivariate Cox regression analysis demonstrated that T-stage, lymph node ratio >0.20, the presence of extracapsular lymph node involvement, but not complications were significant factors for the prediction of death due to cancer recurrence. However, in the patients who died, multivariate Cox regression analysis demonstrated that not only the presence of extracapsular lymph node involvement but also the occurrence of complications were significantly related with a shorter time interval until death due to recurrence. CONCLUSION: The relation between perioperative complications and cancer recurrence per se is not causal. However, postoperative complications are independently associated with the early timing of death due to cancer recurrence. A possible explanation for this phenomenon is that immunologic host factors enhance microscopic residual disease to develop more rapidly into clinically manifest recurrence.

Surgical symposia during the 14th UEGW, Berlin, Germany, 2006 (Article)

2007-06-01T00:00:00Z

Referral pattern and timing of repair are risk factors for complications after reconstructive surgery for bile duct injury (Article)

2007-05-01T00:00:00Z

BACKGROUND: The aim of the present study was to assess the role of the referral pattern and the timing of the surgical procedure on outcome after reconstructive surgery for bile duct injury (BDI). SUMMARY BACKGROUND DATA: BDI after laparoscopic cholecystectomy remains a major problem in current surgical practice. Controversy exists about the influence of previous interventions before referral and the timing of repair on outcome. METHODS: Of 500 patients referred to a tertiary center, 151 patients (30.2%) underwent reconstructive surgery for BDI. The influence of referral pattern was analyzed by defining patients as primary and secondary referred patients. The influence of timing of repair was investigated by categorizing 3 groups of patients: A, acute repair; B, delayed repair; and C, late repair. RESULTS: Hospital mortality was zero. Perioperative complications occurred in 29 patients (19.2%): in 26.4% in secondary referred patients and 7.9% in primary referred patients (P = 0.04). Perioperative complications occurred in group A in 33.3%, in group B in 15.6%, and in group C in 22.5% (P = 0.22). Postoperative strictures occurred significantly more often in patients operated in the acute phase (P < 0.01) and in secondary referred patients (P = 0.03). A multivariate analysis identified 3 independent negative predictive factors for outcome: extended injury in the biliary tree (odds ratio = 3.70; confidence interval, 1.32-10.34), secondary referral (odds ratio = 4.35; confidence interval, 1.12-16.76), and repair in the acute phase after injury (odds ratio = 5.44; confidence interval, 1.2-24.43). CONCLUSIONS: Reconstructive surgery for the treatment of BDI is associated with acceptable morbidity and no mortality. Extended injury to the bile duct, referral to a tertiary center after therapeutic interventions, and acute repair are independent negative predictors on outcome after reconstructive surgery for BDI.

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial) (Article)

2007-03-22T00:00:00Z

Background. Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. Methods/design. Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). Discussion. The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

Autologous and allogeneic blood transfusions in colorectal cancer (Doctoral Thesis)

1995-06-08T00:00:00Z

Since blood transfusion became a therapeutical option in patient care, the surgical possibilities have increased tremendously. Since the problems of anticoagulation and blood group typing were largely resolved, blood transfusions were in only a minority of cases directly lethal. However, it was estimated that still up to 20% of the blood transfusions induces a sort of adverse side-effect. Because the most important side-effects are a result of the transmission of infections and the induction of immunological reactions, these are further discussed.

Blood transfusions and local tumor recurrence in colorectal cancer. Evidence of a noncausal relationship (Article)

1994-01-01T00:00:00Z

OBJECTIVE. The authors analyzed the effect of blood transfusions on the pattern of colorectal cancer recurrence. BACKGROUND. Retrospective studies suggest that blood transfusions are associated with a poor prognosis in patients who undergo operations for colorectal malignancies. In a previously published, randomized trial, it was investigated whether autologous blood transfusions could overcome this putative detrimental effect. However, this did not appear to be the case. METHODS. In the current study, the authors analyzed the patterns of recurrence in 420 patients who underwent curative operations for colorectal cancer. RESULTS. Patients who did not require transfusions (N = 143) had significantly better disease-free survival than those who did need transfusions (N = 277); percentages at 4 years were 73% and 59%, respectively (p = 0.001). No difference was found between both groups in comparing cumulative percentages of patients having metastases; percentages at 4 years were 25% in the group that did not undergo transfusion and 27% in the transfused group. The percentage of cases having local recurrence, however, was significantly increased (p = 0.0006) in the transfused group as compared with the group that did not undergo transfusion; percentages at 4 years were 20% and 3%, respectively. The groups of patients receiving only allogeneic, only autologous, or both types of transfusions all had a significantly higher incidence of local recurrence than the patients who did not receive transfusions, but no differences were found between these three groups. CONCLUSIONS. These findings suggest that the association between blood transfusions and prognosis in colorectal cancer is a result of the circumstances that necessitate transfusions, leading to the development of local recurrences, but not of distant metastases.