[Position paper on surgical oncology].
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Curriculum↗
Biomedical subjects
H G Beger
Publications and source records attributed to H G Beger.
Diagnosis and staging of pancreatic cancer by positron emission tomography.
The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. Several imaging modalities are now used to diagnose pancreatic cancer, including transabdominal ultrasonography (US), contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography, and selective angiography. None of these six methods is perfect: Each has advantages and disadvantages, and their sensitivity and specificity are in a high range. In 1990 positron emission tomography (PET) was first applied to diagnose pancreatic cancer. This new diagnostic modality is based on functional changes in the pancreatic cancer cells caused by enhanced glucose metabolism. Increased glucose utilization is one of the characteristics of malignantly transformed cells, independent of their origin. The technical development of PET has allowed this new procedure to be used for clinical evaluation. Using 2-((18)F)-fluoro-2-deoxy-d-glucose, PET can identify pancreatic cancer and differentiate pancreatic cancer from chronic pancreatitis with a sensitivity of 85% to 98% and a specificity of 53% to 93%. However, high sensitivity and high specificity are strongly dependent on the tumor stage. At present PET is still experimental and is available only in specialized centers. It may represent a new and noninvasive diagnostic procedure for the detection and the staging of pancreatic cancer. Further clinical studies, especially including patients with early tumor stages (small tumor size), are needed. This review discusses the possibilities and limits of PET and evaluates its importance in the future.
Adenocarcinoma↗
Intraarterial adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic cancer: significant reduction in occurrence of liver metastasis.
The clinical benefit of adjuvant chemotherapy in pancreatic cancer patients is still questionable. Phase II studies using radiochemotherapy based on 5-fluorouracil (5-FU) provided evidence of an increase in median survival times. Because palliative chemotherapy by celiac artery infusion (CAI) led to an increase in survival in pancreatic cancer, we treated 24 patients with adjuvant CAI following resection of the head of the pancreas for pancreatic cancer (21 patients with Union Internationale contre le Cancer (UICC) stage III, 2 with UICC stage II, 1 with UICC stage I). Catheters were placed angiographically into the celiac artery and remained there for 5 consecutive days. One cycle of chemotherapy consisted of mitoxantrone, 5-FU, folinic acid, and cisplatinum. This treatment was repeated five times at monthly intervals. CAI was well tolerated, and World Health Organization (WHO) grade III toxicities were observed in 8%; WHO grade IV was seen in none of the treatment cycles. Furthermore, we observed pain reduction in nearly all patients under CAI. Median survival times in patients who received CAI were 23 months for all patients, whereas in patients who did not receive adjuvant treatment the median survival was 10.5 months. With Kaplan-Meier regression analysis of the patients who were curatively resected (R0 resection) and received CAI, the overall 4-year survival was 54%, whereas in patients without CAI the 4-year survival was 9.5%. The occurrence of liver metastases in the CAI group went down to 17%. These results demonstrate that CAI is well tolerated, reduces the risk of liver metastasis, and increases the survival time of pancreatic cancer patients.
Adult↗
Non-operative management of arterial liver hemorrhages.
A retrospective evaluation of embolotherapy in patients with arterial liver hemorrhages was carried out. Twenty-six patients, ranging in age from 10 days to 77 years with active arterial liver hemorrhages, underwent non-surgical embolotherapy. Bleeding was attributed to trauma (n = 21), tumor (n = 3), pancreatitis (n = 1), or unknown cause (n = 1). Twenty-nine embolizations were performed via a transfemoral (n = 26) or biliary (n = 2) approach. One bare Wallstent was placed into the common hepatic artery via to an axillary route to cover a false aneurysm due to pancreatitis. Treatment was controlled in 4 patients by cholangioscopy (n = 2) or by intravascular ultrasound (n = 2). Prior surgery had failed in 3 patients. Intervention controlled the hemorrhage in 24 of 26 (92%) patients within 24 h. Embolotherapy failed in 1 patient with pancreatic carcinoma and occlusion of the portal vein. In 1 patient with an aneurysm of the hepatic artery treated by Wallstent insertion, total occlusion was not achieved in the following days, as demonstrated by CT and angiography. However, colour Doppler flow examination showed no flow in the aneurysm 6 months later. Complications were one liver abscess, treated successfully by percutaneous drainage for 10 days, and one gallbladder necrosis after superselective embolization of the cystic artery. Embolization is a effective tool with a low complication rate in the treatment of liver artery hemorrhage, even in patients in whom surgery has failed.
Adolescent↗
Founding of a German society of Visceral Surgery.
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Digestive System Surgical Procedures↗
Lymph-node dissection in pancreatic cancer -- what are the facts?
BACKGROUND: The surgical therapy of ductal adenocarcinoma of the pancreas is well standardized around the world, with the exception of the extent of the resection of regional lymph nodes and peripancreatic soft tissue. This much-debated issue has become apparent after several Japanese reports that were able to demonstrate better survival after extensive lymph-node clearance. These results, however, could not be achieved using similar techniques in the Western world. The reason for these apparent differences in surgical results result from the application of two different staging systems (UICC and JPS) and the fact that the study designs of the compared trials are not comparable. The most desirable source of information coming from a randomized controlled study is, to date, only available from one trial which was not able to demonstrate a significant survival difference. CONCLUSION: So far, there is no substantial proof that extensive lymph-node clearance is beneficial for the patient. It has been shown, however, that in specialized centers these procedures do not carry an increased risk of perioperative morbidity and mortality compared with standard resections. In those institutions, the efficacy of extended resections needs to be further evaluated in prospective randomized trials, preferably based on the "International Documentation System for Pancreatic Cancer", which allows data acquisition independent of the staging system applied.
Adenocarcinoma↗
Leukocytes, the Janus cells in inflammatory disease.
BACKGROUND: Leukocytes, also called white blood cells, can be categorized into three main groups, granulocytes, monocytes, and lymphocytes, which can be further classified into various subgroups. Lymphocytes are known to intervene in immune responses such as secreting cytokines, killing cells, or the production of antibodies. Monocytes/macrophages participate in chronic inflammation by synthesizing numerous mediators and eliminating various pathogens. DISCUSSION: The main type of granulocytes is the neutrophil, also called the polymorphmononuclear (PMN) leukocyte; these are usually not found in normal "healthy" tissue and are referred to as 'the first line of defense' against invading pathogens. However, besides the beneficial microbicidal activity of neutrophils, this cell type is also involved in the pathophysiology of organ damage in ischemia/reperfusion, trauma, sepsis, or organ transplantation. The exact role or function of leukocytes during inflammatory processes is far from being elucidated and can only be estimated from the enormous amount of literature on these cell types. The present review will focus mainly on PMN leukocytes and their ambiguous role in normal and inflamed tissue.
Antibodies↗
Regional chemotherapy of non-resectable liver metastases from colorectal cancer - literature and institutional review.
BACKGROUND: Cure is possible by resecting colorectal isolated liver metastases. In non-resectable isolated colorectal liver metastases (CRLM), regional chemotherapy has been advocated to optimize the disease control in the liver in order to improve the results of the alternative, systemic chemotherapy. The drugs are delivered by means of hepatic artery infusion (HAI) via ports or pumps; pharmacological modifications of the hepatic arterial blood-flow-like HAI with starch microspheres or stop-flow and perfusion techniques were applied to improve HAI. METHODS: We reviewed the literature and report our progress, up to May 1999, in analyzing the validity of HAI for CRLM therapy. RESULTS: In the majority of phase-II and -III trials, the response rates to HAI were significantly higher than those from systemic chemotherapy, and local disease control could be achieved even when HAI was used second line to systemic chemotherapy. The meta-analysis of randomized trials comparing HAI with either systemic chemotherapy (five trials) or, optionally, either 5-fluorouracil (FU) or symptomatic treatment (two trials) showed a significant advantage of HAI in response (41% vs 14%, P<10(-10)) and median survival time (15 months vs 11 months, P<0.0009). The active anabolite of 5-FU, 5-fluordeoxyuridine (5-FUDR), the drug of choice for HAI in those trials, may cause severe hepatotoxicity. To avoid this toxicity, we developed a HAI protocol using mitoxantrone, 5-FU plus folinic acid (FA) and mitomycin C (MFFM). The response rates of HAI with 5-FU plus FA or MFFM were 45% and 66%, the interim median survival times 19.8 months and 27.4 months. 5-Year survivors were observed in all our protocols. Since no severe hepatotoxicity occurred, 9 of 74 patients were resected after response to HAI with 5-FU plus FA or MFFM, without surgical mortality and with survival times from 2+ months to 58+ months. CONCLUSION: The high response rates, the long survival times, the possibility of achieving 5-year-survival either by HAI alone or by resection after down staging with HAI all sum up to the evidence that HAI could be the primary choice of treatment for CRLM. Phase-III trials are conducted to compare the protocols with optimal regional versus systemic chemotherapy.
Adenocarcinoma↗
Immunotherapy in pancreatic cancer - current status and future.
BACKGROUND: In pancreatic cancer, multimodal protocols, involving chemotherapy, radiation, or regional treatment, are initiated to improve oncological outcome. Since pancreatic adenocarcinoma has been shown to be susceptible to immune stimulation, several immunotherapy approaches have been investigated to define the role of immunotherapy in pancreatic cancer. METHOD: A review of current and past data concerning experimental and clinical immunotherapy in pancreatic cancer is presented in the context of basic immunotherapeutic principles. Past pitfalls and future developments are analyzed and a synthesis of immune stimulation and immune suppression is deduced on the basis of published data. RESULTS: Preclinical and initial clinical studies with monoclonal antibodies CO17-1A, BW494/32 and anti-epidermal growth factor receptor (EGFR) have been conducted, and various targets suitable for immunotherapy have been identified involving new molecular and gene technology. Targets on pancreatic cancer cells currently under investigation are mucins (MUC-1), glycoproteins (GA733), ras peptides and EGFRs. Side effects are minor and rarely auto-immune reactive. Another approach combines randomized regional with systemic chemoimmunotherapy (mitomycin C, 5-fluorouracil, folinic acid, carboplatin, epirubicin; interferon-gamma, interleukin-2) in nonresectable pancreatic cancer and obtains significant differences in median survival rates (14 months vs 4.5 months in controls) and quality of life. CONCLUSION: Although single remarkable improvements in the immunological approach to treatment of pancreatic cancer have been made, immunotherapy in pancreatic cancer is still experimental. On the basis of reliable preclinical data, new immunotherapy protocols will have to be evaluated clinically. Careful monitoring of immune responses and side effects, and assessment of quality of life will ensure identification of effective immunotherapy protocols for human pancreatic cancer in the near future.
Animals↗
Isolation and characterization of a human hepatic epithelial-like cell line (AKN-1) from a normal liver.
The isolation and characterization of human liver cell lines are rather difficult due to limited material and poor growth in cell culture. In this report, we present the isolation, culture and characterization of a new epithelial-like liver cell line (AKN-1) with a heterogeneous cell population and many characteristics of the biliary epithelium. The AKN-1 cell line stained positively with antibodies to epithelial cytokeratin polypetides CK 8, 18, and 19. In addition, the cell line expressed the anti-human epithelial-related antigen (MOC-31), the human epithelial antigen (HEA), and the gamma-glutamyl transpeptidase, the hematopoietic growth factor, stem cell factor, and also its receptor, c-kit. The cell line failed to express albumin and factor 8 by immunohistochemistry. It did show, however, a twofold increase in 7-ethoxyresorufin-O-deethylase activity. Cytogenetic characterization revealed rare breakpoints in chromosome 2, which to our knowledge, have not yet been reported in liver cells.
Biomarkers↗
Intraductal papillary mucinous tumor of the pancreas.
BACKGROUND: Since 1996 the classification of pancreatic tumors was replaced by the new World Health Organization nomenclature. Formerly mucinous cystadenomas are now distinguished between intraductal papillary mucinous tumors of the pancreas (IPMT) and mucinous cystadenomas. METHODS: We reevaluated the pathological specimen and surgical therapy of 23 consecutive patients and followed up these patients up for 4 years in median. Between 1987 and 1997 we treated 8 patients with IPMT and 15 patients with mucinous cystadenomas. RESULTS: Eighty-five per cent of all patients were symptomatic. Ultrasonography and computed tomography were the most sensitive diagnostic techniques. In 25%, the entire pancreas was involved with IPMT; that was not the case in any of the patients with mucinous cystadenoma. All patients were resected with no perioperative mortality. After dismissal from the hospital, all resected patients are still alive after a median follow-up of 4 years. In no patient with IPMT, but in 1 patient with mucinous cystadenoma, the tumor recurred. CONCLUSION: Surgical resection is the treatment of choice in all cystic tumors, and the late outcome of IPMT is as good as for mucinous cystadenoma.
Cystadenoma, Mucinous↗
Surgical management of necrotizing pancreatitis.
In necrotizing pancreatitis, surgical treatment is indicated in patients with infected necrosis. Conservative management should be favored if necrosis remains sterile and the patient responds to intensive care therapy. Different surgical techniques have been established during the past years, including conventional drainage, open and semiopen drainage, and closed management with postoperative continuous lavage of the lesser sac. For experienced physicians, these techniques provide comparable results, and none has been proved to be superior to the others.
Drainage↗
Clinical course after total parathyroidectomy without autotransplantation in patients with end-stage renal failure.
In patients with chronic renal failure, hyperparathyroidism is a common problem and surgical parathyroidectomy (PTX) is frequently required. The three different surgical approaches are subtotal PTX, total PTX with autotransplantation, and total PTX without autotransplantation. Recurrence of hyperparathyroidism varies from 5% to 80% in different studies for the first two surgical approaches. To minimize the risk for recurrence, and because we fear severe relapses with calciphylaxia, we perform total PTX without autotransplantation. From October 1993 to October 1997, 20 patients (9 men and 11 women) underwent total PTX without autotransplantation (median age, 52 years; range, 23 to 74 years; median dialysis time before PTX, 6.5 years; range, 1 to 22 years). All patients were supplemented with vitamin D analogues postoperatively. Patients were followed up for 1 to 48 months (median, 20 months). Bone pain, when present, disappeared within the first week after total PTX. Postoperatively, most patients had temporary hypocalcemia. In the long term, five patients had asymptomatic hypocalcemia. One patient, however, repeatedly had hypocalcemic seizures. Five patients developed asymptomatic hypercalcemia when supplemented with calcitriol. At the end of the individual's observation time, parathyroid hormone (PTH) levels were less than normal in six patients, normal in seven patients, and increased in seven patients despite total PTX. We conclude that total PTX should be reconsidered an option for the treatment of hyperparathyroidism secondary to renal failure. There was no evidence of clinical bone disease after total PTX. Apparently, remaining ectopic parathyroid tissue accounts for PTH levels after total PTX.
Adult↗
Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life.
There is overwhelming consensus that quality of life assessment is urgently required in pancreatic cancer, yet little research has been conducted. We report on the development of a disease specific questionnaire module to supplement the EORTC core cancer module, the QLQ-C30 in patients with pancreatic cancer, using EORTC quality of life study group guidelines for module development. Relevant QoL issues were generated from literature searches and interviews with health professionals and patients with pancreatic cancer. Issues were constructed into items and provisionally translated. The provisional module was pretested in patients in 8 European centres. The resulting module the QLQ-PAN26 includes 26 items related to disease symptoms, treatment side-effects and emotional issues specific to pancreatic cancer. This should ensure that the module will be sensitive to assess the small but important disease and treatment related QoL changes in pancreatic cancer. The use of the QLQ-C30 and QLQ-PAN26 will provide a comprehensive system of QoL assessment in international trials of pancreatic cancer.
Adult↗
A phase II study of high-dose octreotide in patients with unresectable pancreatic carcinoma.
This report describes the results of a phase II trial to evaluate the safety, feasibility and response of patients with irresectable, histologically proven, stage II-IV adenocarcinoma of the pancreas receiving high-dose octreotide treatment. Octreotide was self-administered subcutaneously (3 x 2000 micrograms per day) by 49 patients. Therapy was discontinued after progression of the disease. Due to the subseqment diagnosis of bile duct carcinoma and stage I disease, 2 patients were excluded, leaving 47 evaluable patients with measurable disease. The median Karnofsky score was 80%. 3 patients had stage II (6%), 19 stage III (40%), and 25 (53%) stage IV disease. Octreotide treatment resulted in stable disease in 9 patients (19%) for more than 12 weeks. No complete or partial response was observed. The median overall survival was 21.4 weeks and the median progression-free survival 9.0 weeks. Therapy with high-dose octreotide is feasible, well tolerated and might prolong survival. In a placebo-controlled phase III study the effects of octreotide in patients with pancreatic cancer will be confirmed.
Adenocarcinoma↗
Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis.
BACKGROUND: The risk factors predisposing to organ failure in patients with necrotizing pancreatitis remain unclear. The relationship between the extent of pancreatic necrosis, the presence of infection and the incidence of organ failure was analysed. METHODS: In a retrospective review, the occurrence of pulmonary insufficiency, renal insufficiency, shock, sepsis/sepsis-like syndrome (SLS) and coagulopathy was evaluated in 273 patients with necrotizing pancreatitis, and a comparison was made between patients with sterile or infected necrosis. Additionally, the relation between the incidence of organ failure and extent of pancreatic parenchymal necrosis was investigated by classifying the patients into three groups according to the amount of necrotic tissue found by contrast-enhanced computed tomography (group 1, extent less than 30 per cent; group 2, 30-50 per cent; group 3, more than 50 per cent). RESULTS: Organ failure was more frequent in patients with infected necrosis than in those with sterile necrosis. Differences were found in the incidence of pulmonary insufficiency, sepsis/SLS and coagulopathy. Organ failure occurred more frequently in group 3 than in group 2 or 1 (95 versus 79 and 66 per cent; P = 0.0004). The extent of infected necrosis was not related to the incidence of organ failure (group 1, 88 per cent; group 2, 86 per cent; group 3, 96 per cent). However, there was a relation between the incidence of organ failure and the extent of sterile necrosis (group 1, 59 per cent; group 2, 74 per cent; group 3, 94 per cent; P = 0.0001). Multivariate analysis confirmed the presence of infection and the extent of necrosis as independent determinants of organ failure. CONCLUSION: The incidence of organ failure is determined by both bacterial infection and extent of necrosis. The incidence of organ failure is determined by the extent of necrotic parenchyma in patients with sterile necrosis. Infected necrosis is associated with a high incidence of organ failure irrespective of the extent of necrosis.
Acute Kidney Injury↗
Natural history of acute pancreatitis and the role of infection.
Bacterial infection of pancreatic necrotic tissue is a frequent complication of severe acute pancreatitis. Infected pancreatic necrotic tissue is observed in 30-70% of all patients suffering from necrotizing pancreatitis. It is the leading cause of deaths in severe acute pancreatitis, with mortality rates ranging from 15 to 30%. The incidence of infection increases with the extent of the necrotic areas and with the time after onset of pancreatitis. Compared to patients with sterile necrosis, those with infection of the necrotic areas have an increased mortality, and systemic complications occur more frequently. Standard treatment for infected pancreatic necrotic tissue is surgical debridement, whereas conservative management is feasible in approximately 30% of the patients with sterile necrosis. As bacterial infection of pancreatic necrotic tissue has a tremendous impact on the prognosis of the disease and on the patient's clinical course, efforts have been made to prevent it. Although clinical and experimental data provide evidence that prophylactic antibiotics have beneficial effects on the outcome and course of patients with severe acute pancreatitis, this topic has to be investigated further. General recommendations concerning the early use of antibiotics have to await the results of larger, double-blind studies.
Anti-Bacterial Agents↗
Downstaging by regional chemotherapy of non-resectable isolated colorectal liver metastases.
AIMS: To improve the course of isolated non-resectable colorectal liver metastases (CRLM) by hepatic arterial infusion treatment. Patients with CRLM have a worse prognosis than those whose liver metastases are resectable. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases with 5-fluorouracil+folinic acid (5-FU+FA) i.v. may result in median survival times of 6.4-14.3 months. Hepatic artery infusion (HAI) with 5-fluorodeoxyuridine (5-FUDR) has been demonstrated in a meta-analysis of randomized trials to be superior to i.v. treatment/palliative care (median survival 15 vs. 10 months). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver cirrhosis. We have developed a stepwise protocol for HAI in CRLM, which is superior to HAI with 5-FUDR and to systemic chemotherapy. METHODS: Between 1982 and 1997, 168 CRLM patients were treated within the following protocols. In protocol A, 48 CRLM patients received HAI with 5-FUDR. In protocol B, 46 patients received 5-FUDR i.a. (HAI)+i.v. In protocol C 5-FU+FA were delivered via HAI in 24 patients with CRLM. In protocol D, based on in vitro phase II studies and the results of protocol C, mitoxantrone and mitomycin C were added to 5-FU+FA (MFFM). Fifty (50) CRLM patients received HAI with HFFM. RESULTS: The response rates, median survival time, systemic toxicity and SC rate were: 42%, 20.8 months, 0-19% and 38% for protocol A; 46%, 20.8 months, 0-20% and 41% for protocol B; 45%, 19.8 months, 4-25% and 0% for protocol C; and 66%, 27.4 months, 2-26% and 0% for protocol D. The surgically placed ports for HAI in protocols C and D functioned in 90%, 82% and 76% of patients, 6, 9, and 11 months after beginning HAI. Quality of life in protocol D was high. Nine patients from protocols C and D with either partial (PR, seven patients) or complete (CR, two patients) remissions received a secondary liver resection without hospital mortality, and seven of nine patients are alive 2-58 months after liver resection. The other two died 11 and 22 months after resection. CONCLUSIONS: Optimal treatment of CRLM was found to be protocol D: HAI with MFFM. The results of this protocol, including high remission rate, long median survival time, good port function, good quality of life and, interestingly, the possibility of downstaging and resecting primarily non-resectable metastases, seem to be superior to HAI with 5-FUDR or 5-FU+FA and to systemic chemotherapy with 5-FU+FA. This hypothesis is currently being examined in a phase III study (HAI with MFFM vs. 5-FU+FA i.v.).
Adult↗