Personal observations, opinions, and approaches to cancer of the pancreas and the periampullary area.

This article reviews the diagnosis, staging, surgical, and adjuvant treatment of pancreatic and periampullary cancer based on personal experience covering 25 years. In spite of remarkable progress, especially in regard to staging and surgical treatment, the authors conclude that with the modalities currently available, timely diagnosis and definitive cure of this particular cancer is rare.

[Ultrafast magnetic resonance tomography changes the standard in pancreas diagnosis]. / Die ultraschnelle Magnetresonanztomographie verändert den Standard in der Pankreasdiagnostik.

BACKGROUND: Since the introduction of MRI, including imaging of the hepato-pancreatic duct system (MRCP) and 3D-MR angiography (3D-MRA), new pancreatic diagnostic procedures have been developed. METHODS AND PATIENTS: We report on 143 patients with benign and malignant diseases of the pancreas, who only received MRI preoperatively. All radiologic findings were confirmed intraoperatively. RESULTS: For resectability, MRI obtained sensitivity of 96.0% and specificity of 89.5% and for classification sensitivity of 99.1% and specificity of 95.2%. CONCLUSION: Based on our experience, the benign vs malignant nature of the disease, MRI is a safe and reliable method for pancreatic tumors being able to become the standard diagnostic procedure in the future.

Rare indications for a Kausch-Whipple procedure.

OBJECTIVES: To find out whether the Kausch-Whipple operation is adequate for the cure of rare tumours of the pancreatic head. DESIGN: Retrospective study. SETTING: University hospital, Germany. PATIENTS: Of 640 patients who had Kausch-Whipple procedures between 1972 and 1998 we found 42 (6.6%) who were operated on for rare tumours of the pancreatic head. RESULTS: Among these 42 patients 12 had functioning and non-functioning endocrine tumours, 11 had adenomas that were not locally resectable, 6 had leiomyosarcomas or oncocytomas, 4 had cystadenocarcinomas, 3 had acinar cell carcinomas, 2 had primary lymphomas, and 3 had metastases to the pancreatic head. Operative treatment (such as extended resection), postoperative course, and survival time after operation varied. Patients with adenomas had the most favourable mean survival time of 106.5 months. Among patients with cancer, those with endocrine malignancies had the best outcome with a mean survival duration of 58.3 months.

Sphincter-saving treatment in epidermoid anal cancer: cooperative analysis of 142 patients in five German university surgical centers.

Five southern German university centers cooperated in comparing the effect of surgical vs. nonsurgical therapy strategies on survival and sphincter preservation in the treatment of anal cancer. A standardized questionnaire was used to evaluate retrospectively (mean follow-up 30 months) treatment strategy and outcome (survival, colostomy rate, colostomy-free survival) in patients treated between 1987 and 1996. Of the 142 patients 65% had squamous cell, 20% basaloid, 6% adeno-, and 1% undifferentiated carcinoma (8% histology not recorded); 9% were classified in UICC stage I, 37% in stage II, 25% in stage III, and 4% in stage IV (25% not recorded). Primary treatment consisted of local excision (10%), excision plus radio- and/or chemotherapy (17%), radiotherapy (20%), radiochemotherapy (28%), or colostomy with or without resection, radiotherapy, and chemotherapy (23%). We observed no difference between these treatment groups in overall (P = 0.43) or colostomy-free survival (P = 0.14, log-rank). Primary colostomy was prevented in 77% of cases and decreased over the years. Mean overall survival (in months) was 42 in stage I, 38 in stage II, and 25 in stage III (P = 0.0013); mean colostomy-free survival was 36 in stage I, 26 in stage II, and 16 in stage III (P = 0.0021, log-rank). Outcome was not significantly related to therapeutic strategy (surgery or radio-chemotherapy. Primary surgical and nonsurgical strategies in treating anal cancer thus produced similar results, although radiochemotherapy is usually recommended for sphincter-endangering anal cancer. Challenges to be met in the future include the prevention of metastasis and long-term preservation of anal sphincter function.

HLA-DR expression in acute pancreatitis.

OBJECTIVE: To investigate the role of the monocyte/macrophage system in acute pancreatitis DESIGN: Prospective clinical study SETTING: University clinic, Germany SUBJECT: 37 consecutive patients who presented with acute pancreatitis. MAIN OUTCOME MEASURE: Correlation between function of monocytes measured by HLA-DR expression and outcome RESULTS: Patients were divided into three groups according to outcome: those with severe pancreatitis who died (n = 10), those with severe pancreatitis who survived (n = 15), and those with mild pancreatitis who survived (n = 12). There was a clear and significant difference between those with severe and those with mild disease. HLA-DR expression was initially depressed in both groups, but after the third day of treatment it started to recover significantly in those with mild disease (p < 0.05). The difference was also significant from day 7 onwards between those with severe disease who died and those with severe disease who survived (p < 0.05). CONCLUSION: Monocyte function as measured by HLA-DR expression (CD14+DR+) is reduced in patients with acute pancreatitis and does not recover in patients who are going to die (median < 20 relative antigen density units; RU).

Aortocaval fistula complicating abdominal aortic aneurysm: diagnosis with gadolinium-enhanced three-dimensional MR angiography.

With approximately 150 reported cases, fistulas between the abdominal aorta and inferior vena cava are rare. Preoperative clinical diagnosis of aortocaval fistula is difficult because the classical triad of abdominal pain, pulsatile abdominal mass, and abdominal machinery-like bruit may be absent in up to 50 % of patients. We report a case of aortocaval fistula complicating abdominal aortic aneurysm which was diagnosed preoperatively using breath-hold gadolinium-enhanced three-dimensional MR angiography.

Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation.

BACKGROUND: Epidemiological data implicate that renal transplants from living unrelated donors result in superior survival rates as compared with cadaveric grafts, despite a higher degree of human lymphocyte antigen (HLA) mismatching. We undertook a center-based case control study to identify donor-specific determinants affecting early outcome in cadaveric transplantation. METHODS: The study database consisted of 152 consecutive cadaveric renal transplants performed at our center between June 1989 and September 1998. Of these, 24 patients received a retransplant. Donor kidneys were allocated on the basis of prospective HLA matching according to the Eurotransplant rules of organ sharing. Immunosuppressive therapy consisted of a cyclosporine-based triple-drug regimen. In 67 recipients, at least one acute rejection episode occurred during the first month after transplantation. They were taken as cases, and the remaining 85 patients were the controls. Stepwise logistic regression was done on donor-specific explanatory variables obtained from standardized Eurotransplant Necrokidney reports. In a secondary evaluation, the impact on graft survival in long-term follow-up was further measured by applying a Cox regression model. The mean follow-up of all transplant recipients was 3.8 years (SD 2.7 years). RESULTS: Donor age [odds ratio (OR) 1.05; 95% CI, 1.02 to 1.08], traumatic brain injury as cause of death (OR 2.75; 95% CI, 1.16 to 6. 52), and mismatch on HLA-DR (OR 3.0; 95% CI, 1.47 to 6.12) were associated with an increased risk of acute rejection, whereas donor use of dopamine (OR 0.22; 95% CI, 0.09 to 0.51) and/or noradrenaline (OR 0.24; 95% CI, 0.10 to 0.60) independently resulted in a significant beneficial effect. In the multivariate Cox regression analysis, both donor treatment with dopamine (HR 0.44; 95% CI, 0.22 to 0.84) and noradrenaline (HR 0.30; 95% CI, 0.10 to 0.87) remained a significant predictor of superior graft survival in long-term follow-up. CONCLUSIONS: Our data strongly suggest that the use of catecholamines in postmortal organ donors during intensive care results in immunomodulating effects and improves graft survival in long-term follow-up. These findings may at least partially be explained by down-regulating effects of adrenergic substances on the expression of adhesion molecules (VCAM, E-selectin) in the vessel walls of the graft.

[Combined use of MRI and MR cholangiopancreatography and contrast enhanced dual phase 3-D MR angiography in diagnosis of pancreatic tumors: initial clinical results]. / Kombinierter Einsatz von MRT, MRCP und kontrastverstärkter 2-Phasen 3D-MRA in der Diagnostik von Pankreastumoren: Erste klinische Ergebnisse.

PURPOSE: To evaluate the accuracy of a non-invasive "all-in-one" staging MR method in patients with pancreatic tumors. MATERIAL AND METHODS: 46 patients were prospectively evaluated by a combined MR imaging protocol including breath-hold T1- and T2-weighted pulse sequence, MRCP using a breath-hold 2D-RARE sequence, and breath-hold gadolinium-enhanced dual-phase 3D-MR angiography. RESULTS: All pancreatic tumors were detected by the combination of cross-sectional imaging and MRCP. In spite of the use of MRCP, definitive differentiation between pancreatic carcinoma and chronic pancreatitis was not possible in 3 (6.5%) out of 46 cases. High quality 3D-MR angiograms were obtained in 43 (93.5%) cases. In 6 (13%) patients 3D-MRA showed an aberrant right hepatic artery. The overall accuracy of MRI in assessing extrapancreatic tumor spread, lymph node metastases, liver metastases, and vascular involvement was 95.7%, 80.4%, 93.5%, and 89.1%, respectively. CONCLUSION: Due to its high accuracy, the "all-in-one" MR protocol may become the most important modality after clinical examination and ultrasound in the diagnostic work-up for most patients with suspicion of pancreatic tumors.

Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up.

Despite a superior quality of life and a favorable cost effectiveness, it has not been well established thus far whether renal cadaveric transplantation contributes to superior survival probability of end-stage renal disease patients in Europe, because the mortality rate on dialysis is lower compared with the United States. This analysis was undertaken to compare the mortality of wait-listed patients and transplant recipients during long-term follow-up, including the possibility of a retransplant in a single-center study. The study cohort included 309 consecutive patients, ages 17 to 72 yr, being registered on the waiting list of the Renal Transplantation Center of Mannheim since the initiation of the transplantation program on June 3, 1989. Follow-up was terminated on September 30, 1997, with a mean of 4.15 yr. A total of 144 renal cadaveric transplants (four retransplants) was performed during the follow-up period. A Cox regression model considering the time-dependent exposure to the different therapy modalities was applied for statistical analysis. Patients being removed from the waiting list or coming back to dialysis after transplantation were censored at time of withdrawal or graft failure. Transplantation resulted in a lower hazard ratio, which was 0.36 (95% confidence interval, 0.15 to 0.87) when the hazard of the wait-listed group was taken as 1.00. The underlying incidence rate of death was 0.026 per patient-year (0.032 on dialysis versus 0.016 with functioning graft). Performing the evaluation on an intention-to-treat basis without censoring the lower risk of the transplanted group was still pronounced according to a hazard ratio of 0.44 (95% confidence interval, 0.22 to 0.89). Thus, patients receiving a renal cadaveric transplantation have a substantial survival advantage over corresponding end-stage renal disease patients on the waiting list even in the setting of a single transplantation center where mortality on regular dialysis therapy was comparatively low.

Resection of pancreatic cancer--surgical achievements.

INTRODUCTION: Looking back at the initially dismal record for pancreatic cancer surgery - Whipple himself felt that a 30-35% mortality was justifiable (!) - significant progress has been made. PROGRESS: The operative mortality has fallen below 5% and the serious complications of pancretic resections such as leaks and haemorrhage have been reduced to some 10% and we are better equipped to deal with these if they occur. The 5-year-survival of patients in whom pancreatic cancer was amenable to an R0-resection has risen to 30%. These are the surgical achievements using the standard Kausch-Whipple technique alone. There has been no improvement in these results, either by increasing radicality (regional pancreatectomy) or by reducing it (pylorus-preserving pancreatoduodenectomy). The same can be said of all other modalities of oncological treatment that have been tried so far: adjuvant radiochemotherapy, regional chemotherapy, hormonal or genetic manipulations. PERSPECTIVE: This does not mean that we should reduce efforts at improving early detection of the disease and unravelling its complex molecular biology. On the contrary, the results of surgery alone in spite of all improvements seem to have reached a plateau that gives little cause for complacency.

[Vascular surgery within the scope of visceral surgery-oncologic interventions]. / Gefässchirurgie im Rahmen visceralchirurgisch-onkologischer Eingriffe.

The surgeon dealing with oncological operations within the abdominal cavity will be frequently confronted with vascular problems. These include surgically relevant vascular anomalies, arteriosclerotic changes, tumor infiltration of vessels and iatrogenic vascular lesions. The diagnosis, indications and, above all, the vascular surgical techniques applied during oncological procedures on the pancreas and liver are described in this review.

Hemorrhage after pancreatoduodenectomy.

OBJECTIVE: The authors reviewed the hemorrhagic complications of patients who underwent pancreatoduodenectomies between 1972 and 1996. SUMMARY BACKGROUND DATA: Although recent studies have demonstrated a reduction in the mortality of pancreatic resection, morbidity is still high. Bleeding is a close second to anastomotic dehiscence in the list of dangerous postoperative complications. METHODS: The medical records from a prospective data bank of 559 patients who underwent pancreatic resection at the Surgical Clinic of Mannheim (Heidelberg University) were analyzed in regard to postoperative hemorrhagic complications. Differences were evaluated with the Fisher exact test. RESULTS: The overall mortality rate was 2.7%. Postoperative bleeding occurred in 42 patients (7.5%), with 6 episodes ending fatally (14.3%). Erosive bleeding after pancreatic leak was noted in 11 patients (26.2%), 4 of whom died. Gastrointestinal hemorrhage occurred in 22 patients, and operative field hemorrhage was present in 20 cases. Relaparotomy was necessary in 29 patients. An angiography with interventional embolization for recurrent bleeding was performed in three patients. Seven hemorrhages (4.6%) occurred after pancreatectomy for chronic pancreatitis and 35 episodes of bleeding (8.6%) were encountered after pancreatectomy for malignant disease. Obstructive jaundice was present in 359 patients (63.9%). In this group of patients, 32 (8.9%) postoperative hemorrhages occurred. Preoperative biliary drainage did not influence the type and mortality rate of postoperative hemorrhage in jaundiced patients. CONCLUSION: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. Preoperative biliary drainage does not lower postoperative bleeding complications in jaundiced patients. Continuous, close observation of the patient in the postoperative period, so as to detect complications in time, and expeditious hemostasis are paramount.

[Magnetic resonance tomography in diagnosis of vascular infiltration in malignant pancreas tumors]. / Magnetresonanztomographie in der Diagnostik von Gefässinfiltrationen bei malignen Pankreastumoren.

This study was undertaken to evaluate the accuracy of magnetic resonance angiography (MRA) in assessing venous or arterial infiltration in pancreatic cancer. In 90 patients MRA showed a sensitivity of 81.1%, a specificity of 90.2% and an accuracy of 85.9% in predicting venous infiltration and a sensitivity of 81.8%, a specificity of 90.7% and an accuracy of 88.1% in predicting arterial infiltration. From these data we conclude that MRA is an accurate method for detecting vascular infiltration in pancreatic cancer.

[Pancreatic carcinoma--conclusions and prospects]. / Pankreaskarzinom--Schlussfolgerungen und Perspektiven.

Whereas no progress has been made in the diagnosis of early tumors, the staging of pancreatic cancer has improved, mainly through the introduction of ultrafast MRI, resulting in a higher resection rate. The early results of standard pancreatectomy are now excellent (operative mortality < 2.5%). The late results after R0 resections are improving (> 30% 5-year survival), but they are poor overall. So far, extended surgical techniques have not brought any improvement here. Unfortunately, so far adjuvant radiochemotherapy has not proved effective in a recent randomized controlled trial. Molecular and genetic research has deepened our understanding of the cancerogenesis of pancreatic cancer without leading to clinical consequences so far.

Surgery for early gastric cancer: a European one-center experience.

Between 1972 and 1995 a total of 251 patients with early gastric cancer underwent resection in our department of surgery. At the time of the operation 10.8% of the patients were proved to have lymph node involvement, and two already had distant metastases. A subtotal gastric resection was performed in 59.8% of cases (n = 150), a total gastrectomy in 33.8% (n = 85), and either a proximal or an atypical resection in 6.4% (n = 16). Since 1985 subtotal distal resection and total gastrectomy were accompanied by a systematic lymphadenectomy of compartments I and II. The overall postoperative morbidity was 18.3%, and the hospital mortality, 4.9%; it was only 1.6% within the last decade. Concerning these short-term results there were no statistically significant differences between the different surgical procedures. The cumulative overall 5-year-survival rate was 82.6%. There was no statistically significant influence of either the different surgical procedures or the histologic types according to the Japanese classification of early gastric cancer.

Ultrafast magnetic resonance imaging improves the staging of pancreatic tumors.

OBJECTIVE: This prospective study was undertaken to evaluate the accuracy of a noninvasive "all-in-one" staging method in predicting surgical resectability in patients with pancreatic or periampullary tumors. SUMMARY BACKGROUND DATA: Despite progress in imaging techniques, accurate staging and correct prediction of resectability remains one of the chief problems in the management of pancreatic tumors. Staging algorithms designed to separate operable from inoperable patients to save the latter an unnecessary laparotomy are becoming increasingly complex, expensive, time-consuming, invasive, and not without risks for the patient. METHODS: Between August 1996 and February 1997, 58 consecutive patients referred for operation of a pancreatic or periampullary tumor were examined clinically and by 5 staging methods: 1) percutaneous ultrasonography (US); 2) ultrafast magnetic resonance imaging (UMRI); 3) dual-phase helical computed tomography (CT); 4) selective visceral angiography; and 5) endoscopic cholangiopancreatography (ERCP). The assessment of resectability by each procedure was verified by surgical exploration and histologic examination. RESULTS: The study comprised 40 male and 18 female patients with a median age of 63 years. Thirty-five lesions were located in the pancreatic head (60%), 11 in the body (19%), and 1 in the tail of the gland (2%); there were 9 tumors of the ampulla (16%) and 2 of the distal common duct (3%). All five staging methods were completed in 36 patients. For reasons ranging from metallic implants to contrast medium allergy or because investigations already had been performed elsewhere, US was completed in 57 (98%), UMRI in 54 (93%), CT in 49 (84%), angiography in 48 (83%), and ERCP in 49 (84%) of these 58 patients. Signs of unresectability found were vascular involvement in 22 (38%), extrapancreatic tumor spread in 16 (26%), liver metastases in 10 (17%), lymph node involvement in 6 (10%), and peritoneal nodules in only 2 patients (3%). These findings were collated with those of surgical exploration in 47 patients (81 %) and percutaneous biopsy in 5 (9%); such invasive verification was deemed unnecessary and therefore unethical in 6 clearly inoperable patients (10%). In assessing the four main signs of unresectability (extrapancreatic tumor spread, liver metastases, lymph node involvement, and vascular invasion), the overall accuracy of UMRI was 95.7%, 93.5%, 80.4%, as compared to 85.1%, 87.2%, 76.6% for US and 74.4%, 87.2%, 69.2% for CT. In assessing vascular invasion, the sensitivity, specificity, and overall accuracy of angiography were 42.9%, 100%, and 68.8%, respectively. There were 3 complications (12.5%) after 24 resections, 5 in 17 palliative procedures, and none after 6 explorations only. The hospital stay was 14 days after resection, 13 after palliative bypass, and 6 after exploration alone. There was no operative or hospital mortality in these 58 cases. CONCLUSIONS: Although it is by no means 100% accurate, UMRI is equal or even superior to all other staging methods. It probably will replace most of these, because it provides an "all-in-one" investigation avoiding endoscopy, vascular cannulation, allergic reactions, and x-radiation. But because even UMRI is not perfect, the final verdict on resectability of a tumor still will depend on surgical exploration in some cases.

The role of laparoscopy in the preoperative staging of pancreatic carcinoma.

Between January 1990 and December 1995, a total of 398 patients underwent laparotomy for pancreatic or periampullary carcinoma at the Surgical Clinic of Mannheim. The tumor was located in the pancreatic head in 290 patients (72.9%), in the body of the pancreas in 42 patients (10.6%), and in the pancreatic tail in 19 patients (4.7%). Forty-seven patients (11.8%) presented with periampullary carcinoma. The preoperative diagnostic workup included abdominal ultrasound, CT scan, endoscopic retrograde cholangiopancreatography, and angiography. One hundred seventy-two patients (43.2%) underwent a tumor resection, 150 (37.7%) had a palliative bypass operation, and 76 (19.1%) underwent only an exploratory laparotomy. Preoperative diagnosis had predicted unresectability in 66 (87%) of the patients who underwent exploratory laparotomy. In 76 patients the intraoperative findings showed an unresectable tumor, which was located in the head of the pancreas in 54 cases (71%), in the body of the pancreas in 17 (22.4%), in the tail region in four (5.3%), and in the periampullary region in one (1.3%). Local signs of unresectability were found in 47 patients (62%) and peritoneal or hepatic metastases in 29 (28.2%). Given that local inoperability can be reliably assessed only at laparotomy, this leaves just 29 (7%) of 398 patients who did not require palliation and whose signs of unresectability could possibly have been discovered by means of the laparoscopic approach. Laparoscopy (including laparoscopic ultrasound) should be used selectively in patients considered probably unresectable who do not require a palliative procedure immediately before the planned operation.

[Guidelines in therapy of pancreatic carcinoma]. / Leitlinien zur Therapie des Pankreaskarzinoms.

The definition of guidelines as merely describing a "corridor of action" and the existence of numerous up-to-date textbooks on the subject raises the question as to their purpose and necessity. This paper provides a critical commentary on existing guidelines. Above all it points out that the sections on preoperative diagnosis and palliative surgery require amendments barely 8 months after publication of the guidelines. Thus while the compilation of guidelines is laudable, it is both expensive and time-consuming, and this problem is potentiated by the need for constant amendment.