Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin.

The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m(-2) and leucovorin 20 mg m(-2) both given as intravenous bolus injection on days 1-4, plus cisplatin 20 mg m(-2) administered as 90-min infusion on days 1-4. Treatment courses were repeated every 4 weeks x 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of > or = 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3-32), and median overall survival was 14.0 months (range 3-45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted.

Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma.

Adjuvant chemotherapy with fluorouracil (FU) and levamisole or FU/leucovorin (LV) has been established as effective adjuvant treatment for patients with stage III colon cancer. Among several other promising treatment strategies in resected colon cancer, intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation. To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole, the present randomized study was initiated. A total of 241 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned to 'standard therapy' with FU and levamisole, given for a duration of 6 months, or to an investigational arm, consisting of LV 200 mg m(-2) plus FU 350 mg m(-2), both administered intravenously (days 1-4) and intraperitoneally (days 1 and 3) every 4 weeks for a total of six courses. In patients with stage II disease, no significant difference was noted between the two arms after a median follow-up time of 4 years (range 2.5-6 years). Among 196 eligible patients with stage III disease, however, a comparative analysis of the two treatment groups suggested both an improvement in disease-free survival (P = 0.0014) and a survival advantage (P = 0.0005), with an estimated 43% reduction in mortality rate (95% confidence interval 26-70%) in favour of the investigational arm. In agreement with its theoretical rationale, combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement (9 vs 25 patients in the FU/levamisole arm; P = 0.005). Treatment-associated side-effects were infrequent and generally mild in both arms, although a lower rate of severe (WHO grade 3) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy (3% vs 12%; P = 0.01). The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma.

Fluorouracil plus racemic leucovorin versus fluorouracil combined with the pure l-isomer of leucovorin for the treatment of advanced colorectal cancer: a randomized phase III study.

PURPOSE: To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS: A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier. RESULTS: There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms. CONCLUSION: The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.

Flushable exo-endodrainage: a modified palliative approach to non-resectable malignant biliary obstruction.

The introduction of new imaging techniques has markedly improved the diagnosis of hepatobiliary disorders. Due to their anatomic situation, a substantial percentage of malignancies located near the hilus is not suitable for surgical management. We discuss an effective palliative intervention to relieve jaundice. In many instances drainage is a superior choice when biliodigestive anastomoses are not technically feasible and palliative resection carries a high complication rate. We present an irrigatable exo-endodrainage method employing a modified port-a-cath system as a new alternative. In four patients, all older than 75 years, this system was implanted because of jaundice due to unresectable malignant stenosis of the extrahepatic bile duct. One patient (80 years old) died of pre-existing acute necrotizing pancreatitis, although hyperbilirubinemia was found to decrease on the 7th postoperative day. The other three patients showed complete normalization of their bilirubin levels and their port-a-cath systems remained open until their death (at 3 weeks, 6 months and 7 months respectively).

[Treatment of Fournier's gangrene. A review based on 3 new cases]. / Die Behandlung der Fournier'schen Gangrän. Eine Ubersicht anhand von 3 neuen Fällen.

We describe three new cases of Fournier's gangrene-a necrotizing fasciitis of urogenital or anorectal origin. Though in the initial report the disease was believed to be idiopathic, the source of infection or immuncompromising factors can be identified in nearly all cases today. We present a combination of aggressive surgical therapy and adjunctive use of Imipenem which was successful in the treatment of all our cases. By using fully resorbable nutrition colostomy could be avoided successfully.

A phase II trial of 5-fluorouracil, leucovorin, and recombinant alpha-2b-interferon in advanced adenocarcinoma of the pancreas.

BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.

Long term analysis of factors influencing the outcome in carcinoma of the breast smaller than one centimeter.

We evaluated established risk factors (tumor size, lymph node status, menopausal status, estrogen receptor status, tumor histology and grading according to Bloom and Richardson, including subfactor analysis), as well as the influence of local procedures, in 138 patients with primary carcinoma of the breast smaller than 1 centimeter. The patients were operated upon during 1969 to 1989 at the Department of Surgery, Hanusch Medical Center, Vienna. Twenty-two patients had a recurrence after a median observation time of 15 years. Seven patients died of the primary disease by the control date (31 May 1990). Grading (p = 0.01, 0.0044) as well as nuclear polymorphism (p = 0.003, 0.00001) and mitosis rate (p = 0.02, 0.01) proved to be significant parameters for recurrence free survival and overall survival. Local procedures (modified radical mastectomy, breast conserving operation with or without postoperative radiotherapy) revealed borderline significance with local recurrence free survival (p = 0.08). All other parameters were without any statistical significance (Mantel-Cox log rank test). Our data confirm the superior prognostic relevance of histologic grading and nuclear polymorphism in patients with carcinoma of the breast smaller than 1 centimeter. High grade nuclear polymorphism as a subfactor in the grading classification according to Bloom and Richardson appears to be a highly valid risk factor for this entity.

Partial pancreaticoduodenectomy (Whipple procedure) for pancreatic malignancy: occlusion of a non-anastomosed pancreatic stump with fibrin sealant.

Following partial pancreaticoduodenectomy for periampullary and pancreatic cancer, the complication and mortality rates are particularly high. Various approaches have aimed at improving the postoperative result, with less than complete success. The discouraging results of others, and our own dissatisfaction, led us to evaluate an atraumatic, sutureless method for management of the residual gland. Following head resection, the remaining pancreas is occluded with a fibrin sealant (Tisseel c, Immuno AG, Vienna) via injection into the pancreatic duct, which is then ligated and left free in the peritoneal cavity. Among 44 patients treated with this method, there were no perioperative deaths. Three patients developed local complications (2 fistulae, 1 pancreatitis) due to technical errors that presumably resulted in incomplete occlusion. Evaluation of patients after two to three years indicates that the endocrine function of the pancreas has been largely conserved despite ductal occlusion.

Local gentamicin application for perineal wound healing following abdominoperineal rectum excision.

A major complication of abdominoperineal rectum excision for rectal or anal carcinoma is local wound infection. The main reason for this infection is that systemically administered antibiotic prophylaxis does not reach sufficiently high concentrations of antibiotic in the tissue of the sacroperineal wound. Since gentamicin-polymethylmethacrylate (PMMA) in the form of chains of beads has been confirmed as a useful tool in the treatment of local infection in bone and soft tissue surgery, we have evaluated its effect on the abdominoperineal rectum excision in a prospective, randomized trial. Forty-four patients with rectal or anal carcinoma entered the study. Only patients with stage Dukes D were excluded from the trial. Following randomized selection, the patients were treated either with local gentamicin and drainage (Group A) or drainage alone (Group B), using the Lloyd-Davies procedure. The two groups were comparable regarding age, sex, tumor stage and level, and risk factors predisposing for an infectious complication (anemia, nutritional status, blood transfusion). The postoperative mortality rate was 0% in both series. Analysis of local perineal wound healing revealed a statistically significant higher percentage of primary wound healing in Group A than in Group B (87% versus 46%; p less than 0.01). This led to a significantly shorter hospitalization period for patients in Group A (p less than 0.01). Gentamicin-PMMA chains have been demonstrated to exert a favorable effect on local wound healing and the postoperative outcome of patients with abdominoperineal rectum excision.

Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.

Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.

Diagnosis and tactical approach to surgery for early gastric carcinoma: a retrospective analysis of the past 16 years in an Austrian general hospital.

In principle, many authors advocate a radical surgical approach for early gastric cancer (gastrectomy on principle). Our own experience with subtotal gastrectomy (including N1 + N2 lymphadenectomy; limited resection even without groups 11, 12) shows that this method yields comparable results. With an operative mortality of 2%, the survival rate was 84.3% after 5 years and 70.5% after 10 years, instead of the predicted values of 82.8% and 63.4%, respectively. Applied to the same age group without gastric carcinoma, this yields a 5-year survival rate of 101.8% and thus almost reaches Japanese standards.

[Splenectomy in idiopathic thrombocytopenic purpura]. / Splenektomie bei idiopathisch-thrombocytopenischer Purpura (ITP).

In the period between 1978 to 1987 16 female and 11 male patients with a median age of 35 years (range: 14 years to 85 years) underwent splenectomy for ITP. There was no lethality in the postoperative period. 77.8% of all patients are in a complete remission, only 22.2% showed a recurrence and need further conservative therapy.

[Lymphomas of the gastrointestinal tract]. / Lymphome des Gastrointestinaltrakts.

Recent progress in polychemotherapy employed in the treatment of gastrointestinal lymphomas has markedly improved prognosis. Between 1980 and 1986, 22 patients with malignant lymphomas of the gastrointestinal tract were treated at the Department of Surgery at the Hanusch Medical Center, in cooperation with the Department of Hematology and Oncology. 19 patients underwent surgery. The average observation time was 29 months. The rate of survival after 36 months was 64% in the entire patient population. Palliative-surgical interventions combined with chemotherapy equally produced satisfactory results.

[Plasma exchange in acute abdomen with multiple organ failure--a case report]. / Plasmaaustausch bei akutem Abdomen mit Polyorganversagen--ein Fallbericht.

Following four weeks of conservative treatment of acute pancreatitis a 43 years old female was admitted to our ICU in severe circulatory shock (MAP less than 50 mmHg despite dopamine and dobutamine 5 mcg/kg/min, and norepinephrine 0.4 mcg/kg/min), respiratory failure, incipient renal failure and coma. Laboratory examination revealed thrombopenia (14 G/l) and leucopenia (0.5 G/l), as well as impaired prothrombine time (20%) and partial thromboplastine time (greater than 2 min). As abdominal sepsis was suspected to be the most likely cause of the patients multiple organ failure, a laparotomy was planned. To improve coagulation prior to surgery, plasmapheresis was performed exchanging 4.8 liters of plasma with fresh frozen plasma. In addition 3 units of platelets were transfused. The effects of the plasmapheresis were an improvement of circulatory as well as coagulatory parameters. Laparotomy revealed toxic megacolon, whereas the pancreas seemed to be normal; a coecostomy and a transversostomy were performed. The patient thereafter improved gradually; catecholamine doses were reduced, renal function recovered and five days postoperatively weaning from the ventilator was possible. Platelet substitution (6 more units), fresh frozen plasma administration (76 units à 200 ml) and AT III substitution (total 10,500 U) had to be continued throughout the first week. Five weeks after this operation, which would have been impossible without preoperative plasmapheresis, the patient was discharged in good health.

[Extragenital endometriosis--abdominal manifestations and complications (a general review)]. / Endometriosis extragenitalis--Abdominelle Manifestationen und Komplikationen (Ein Ubersichtsreferat).

This paper describes the aetiology, symptoms, diagnosis and therapeutic management of extragenital endometriosis and discusses the abdominal complications on the basis of the case histories of several patients with severe manifestation of this condition.

[Consecutive series of 100 colonic resections with a modified continuous suture technic]. / Konsekutive Serie von 100 Colonresektionen mit einer modifizierten fortlaufenden Nahttechnik.

Based on a consecutive series it is reported about a modified type of "continuous" suture on the colon, used especially in elderly patients for being a secure and prompt method of anastomosing. The rate of insufficiency and mortality, as far as the clinical relevance is concerned, turns out to be 2% each and there was no relation between mortality and insufficient anastomosis. The complication rate was 11%, whereby the urological complications predominated with 6% of the total.

[New facts on haemostasis by using fibrin adhesive in abdominal surgery]. / Erfahrungen bei der Blutstillung mittels Fibrinklebers in der Abdominalchirurgie.

In each one of our 34 different cases in which we used the fibrin adhesive on parenchymatous tissue, we were successful in obtaining immediate haemostasis. Although the number of cases studied is rather small, the good results are encouraging.