Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.

To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.

[Surgical resection of primary lung cancer. A 13-year experience in Geneva]. / Chirurgie d'exérèse du cancer pulmonaire primitif. Expérience genevoise de 13 années.

This retrospective study concerns 683 consecutive patients operated for primary non-small cell lung cancer between 1977 and 1989 (581 men and 102 women with a mean age of 60.3 years). Histology was as follows: squamous in 422 (62%), adenocarcinoma in 207 (30%), broncho-alveolar in 24 (4%) and large-cell in 30 (4%). According to the TNM classification, 304 tumors were graded as stage I (45%), 130 as stage II (19%), 157 as stage IIIA (23%), 62 as stage IIIB (9%) and 19 as stage IV (3%). Surgery consisted of lobectomies in 337 (49%), pneumonectomies in 210 (31%), segmentectomies and wedge resections in 42 (6%), bilobectomies in 41 (6%) and exploratory thoracotomies in 53 (8%). It was curative in 513 cases (75%) and palliative in 170 (25%). 49 patients died within 2 months of the operation (7.2%), while 209 suffered postoperative complications (31%). Mediastinal lymph node dissection was not routinely performed to in this series. However global outcome (30% 5 years survival and 18% at 10 years), compared favorably with that reported by centres that perform mediastinal lymphadenectomy systematically.

Early hematological toxicity of adjuvant perioperative intraportal and intravenous chemotherapy with fluorouracil, mitomycin and heparin in colorectal cancer. Swiss Group for Clinical Cancer Research.

BACKGROUND: From 1987 to 1993 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III adjuvant trial in patients with colorectal adenocarcinoma with the objective of comparing intraportal versus intravenous perioperative chemotherapy. PATIENTS AND METHODS: Patients younger than 75 years had a curative en bloc resection of their cancer and were then randomized into three arms: 1. adjuvant perioperative portal liver infusion with fluorouracil, mitomycin and heparin, 2. adjuvant subclavian intravenous infusion with the same regimen and 3. no adjuvant treatment. The hematological toxicity was evaluated by hemoglobin determination and leucocyte and thrombocyte counting before and during ten days after surgery. RESULTS: Hemoglobin showed a median decrease of 22% in the control group. This decrease is aggravated significantly by 3% through the chemotherapy. Leucocytes showed a median decrease of 7% in the control group. Perioperative chemotherapy caused a significantly higher median drop; 23% when given into the liver through the portal vein and 34% when given systemically through a subclavian catheter. Thrombocytes revealed a median decrease of 25% in the control group. Chemotherapy was not associated with a significant additional drop. CONCLUSIONS: Adjuvant perioperative chemotherapy with fluorouracil, mitomycin and Heparin as given in this study is associated with a significant mild drop in hemoglobin and leucocytes during the first 10 postoperative days. If drug dose increases are planned in future trials the addition of hematopoietic growth factors might be considered.

[Cephalic duodenopancreatectomy for pancreatic adenocarcinoma]. / Duodénopancréatectomie céphalique pour adénocarcinome pancréatique.

Cephalic duodenopancreatectomy is certainly the operation of choice in cases of adenocarcinoma of the pancreatic head. We evaluated the results of this operation in order to justify its indication and to pinpoint the factors that have an influence on the patients' prognosis after the operation. From 1982 to 1992, 386 patients were hospitalized in our department with the diagnosis of pancreatic cancer, all histological types included. Of these, 21 men and 18 women, mean age 65 years, underwent cephalic duodenopancreatectomy for adenocarcinoma. Associated with these operations were 3 liver metastasis excisions, 2 vascular resections, 1 colectomy and 1 splenectomy. All the tumors were operated on whenever technically possible, except those associated with distant metastasis. Postoperatively, only one patient died (on the 29th day, of viral meningitis). Postoperative morbidity was 51% with 23% local complications. There was one leakage of the anastomosis. Age, weight loss, history of pancreatitis or cirrhosis, anesthetic risk (ASA) and tumor staging were not found to be factors increasing the risk of postoperative complications. Survival after 1 year was 34% and after 5 years 6%. The degree of histological differentiation was the only factor that had any significant influence on the postoperative survival rate in our study. We conclude that cephalic duodenopancreatectomy is the treatment of choice which is capable of improving the quality, and to a lesser extent the length, of survival of patients suffering from pancreatic cancer, with acceptable postoperative mortality and morbidity rates.

[Status of portal perfusion in colorectal cancer. Swiss Study Group for Clinical Cancer Research]. / Stellenwert der portalen Perfusion beim colorectalen Carcinom. Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK).

533 patients with diagnosis of operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C (MMC) and 5-Fluorouracil (5-FU) starting immediately after operation, or no adjuvant treatment. Of these, 505 (94%) were evaluable. Over the median follow-up of 8 years, the adjuvant therapy reduced the risk of recurrence by 22% (Hazard ratio = 0.78%, 95% CI 0.61-0.99; P = 0.045). The relative reduction of relapse on death was similar in all subgroups (i.e. nodal status, localization). However, adjuvant portal chemotherapy proved to be most efficient in the subgroups of patients with tumor involvement of the regional lymph nodes (Dukes C) and of patients with colon cancer. Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (i.e. local relapses, liver metastases and/or other distant metastases) in the treated group, rather than to liver relapses alone. We conclude therefore, that part of significant benefit obtained for patients with operable colorectal carcinoma treated with a single course of adjuvant chemotherapy via the portal vein might be due to the additional systemic effects of the portal chemotherapy and further study of perioperative treatment with and without prolonged chemotherapy appears worthwhile.

Chemoradiotherapy versus radiotherapy alone for anal cancer: a retrospective comparison.

PURPOSE: To evaluate the effect of adding one cycle of concomitant chemotherapy to curative radiotherapy on tumor control and toxicity in the treatment of anal cancer. METHODS AND MATERIALS: One hundred twenty-five patients completed curative sphincter-conserving treatment, 57 with radiotherapy alone and 68 with concomitant chemo-radiotherapy. Compared with chemoradiotherapy patients, radiotherapy patients were older (median age 71 vs 63) and had less advanced tumors (T3-4 26% vs 51%). Radiotherapy patients were usually treated with a direct perineal cobalt field (mean dose 31 Gy at 5 cm/10 fractions/3 weeks), complemented in most cases by a sacral are field, followed (mean split 54 days) by Iridium-192 implantation (mean dose 23 Gy, Paris system). The large majority of chemoradiotherapy patients received antero-posterior opposed 10 MV photon fields, including pelvic and inguinal nodes (mean dose 38 Gy/19 fractions/4 weeks), followed (mean split 42 days) by implant boost (mean dose 18 Gy). In addition, chemo-radiotherapy patients received starting on day 1 an IV bolus of Mitomycin-C, 0.4 mg/kg (maximum 20 mg) and a 5-day continuous infusion of 5-fluorouracil 600-800 mg/m2/day. Median follow-up was 65 months for radiotherapy and 48 months for chemo-radiotherapy patients. RESULTS: For all 125 patients at 5 years, overall survival was 65.5%, definitive local control 83% and local control with sphincter preservation 68%. Overall and stage for stage, there was no difference in overall, progression-free or cancer-specific survival, nor in local control, local-regional control, or sphincter preservation rates between patients treated with chemoradiotherapy vs. radiotherapy alone. There was no significant difference between the two groups regarding acute or late toxicity. CONCLUSION: This retrospective analysis does not confirm the efficacy of one course of simultaneous Mitomycin-C and 5-fluorouracil, at least in association with full-dose radiotherapy incorporating Iridium-192 boost.

[Surgery of digestive system cancers in patients over 80 years of age]. / Chirurgie des cancers digestifs chez les patients de plus de 80 ans.

231 patients over 80 years old were operated at the Clinique de chirurgie digestive of Geneva University Hospital between 1981 and 1990 for a malignant tumor of the gastrointestinal tract. The following parameters were studied: intra- and postoperative morbidity and mortality, duration and quality of survival. Surgery proved valid in this age group given its low mortality (15%). Postoperative morbidity (44%) did not prolong hospital stay, since 90% of all patients were discharged within one month of surgery. Following surgery, quality of life was excellent: 75% of patients returned home, and 80% were better off than pre-operatively. Such operations provide better results in term of mortality and survival when performed on an elective basis and curatively.

[Multiple tumors of colon and rectum]. / Les tumeurs multiples du côlon et du rectum.

The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was 1.1% and that of metachronous carcinomas 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinoma was observed. The 5-year actuarial survival in case of curative resection was 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions.

[Multiple tumors of the colon and rectum]. / Les tumeurs multiples du côlon et du rectum.

The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with a carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was of 1.1% and that of metachronous carcinomas of 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinomas was observed. The 5-year actuarial survival in case of curative resection was of 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions.

Clinical evaluation of the CORDIS vascular access port systems: a multicenter study.

Two non-metallic vascular access port systems, the Multipurpose Access Port (MPAP) and Miniport, developed by CORDIS S.A., France, have been evaluated clinically in 78 cancer patients. During the investigational period covering a total experience of 369 treatment cycles and 1,370 infusion days, no cases of infection or septicemia were observed. Serious complications such as drug extravasation and catheter occlusion occurred, although the incidence was relatively low (+/- 1%) when compared with the number of treatment courses (cycles), but in relation to the number of patients included in this study, the procedure-related complication rate was 17.5% for the MPAP and 15.8% for the Miniport. Procedure-related complications can be avoided by proper handling and use of suitable drug combinations to minimize crystallization reactions within the port-catheter systems. The final complication rate (total minus procedure-related) in terms of termination of treatment, i.e. explantation of the port-catheter system was 12.1% for the MPAP and 12.5% for the MINIPORT, which generally confirms the results of other groups. More than 87% of both port-catheter systems were still functional at the end of evaluation.

[Stomach adenocarcinoma: what form of gastrectomy?]. / Adénocarcinome gastrique: quelle gastrectomie?

Three hundred and sixty consecutive cases of gastric adenocarcinoma were studied retrospectively between 1976 and 1987. Surgery was curative in 195 patients: 91 had a subtotal gastrectomy 83 a total gastrectomy and 21 a proximal gastrectomy. Subtotal and total gastrectomy were compared within this group in terms of postoperative morbidity and mortality, abdominal comfort and 5-year actuarial survival: Postoperative mortality was greater after total gastrectomy (9.6 vs 2.2%, p = 0.04), as were anastomotic leaks (19 vs 2%, p = 0.0009). Mean weight loss was greater after total gastrectomy (p = 0.005). Comparison of patients with similar tumor staging and localization did not show any significant difference in 5-year actuarial survival. If subtotal gastrectomy is certainly justified for distal gastric cancer, it should be considered for some proximal localization.

Colon carcinoma immunoscintigraphy by monoclonal anti-CEA antibody labeled with gallium-67-aminooxyacetyldeferroxamine.

Previous experimental results in nude mice showing that radiolabeling the monoclonal antibody anti-CEA 35 with 67Ga-aminooxyacetyldeferroxamine could give better tumor localization than radioiodination prompted us to initiate the present clinical study. The 67Ga-labeled antibody anti-CEA 35 (185 MBq, 0.7-1.7 mg) was injected preoperatively into 14 patients for colorectal carcinoma imaging. The same antibody labeled with 125I (3.7 MBq, 0.25 mg) was injected simultaneously to compare the 67Ga and 125I dose recoveries in surgical specimens. Twelve of 14 primary tumors gave a positive 67Ga scintigraph. The mean %ID/g recovered in all tumors 3-9 days after injection was significantly higher for 67Ga (0.019%) than for 125I (0.005%) (p < 0.001, paired t test). The tumor-to-normal tissue ratios were generally higher for 67Ga, with the exception of liver. We conclude that 67Ga-aminooxyacetyldeferroxamine improved immunoscintigraphy outside the liver, particularly in the pelvic region. We also show that deferroxamine infusion accelerates the excretion of 67Ga in eight patients and propose that this could lead to further improvement of immunoscintigraphy.

Results of surgical palliation for cancer of the head of the pancreas and periampullary region.

Between 1977 and 1986, 101 patients underwent surgical bypass for periampullary carcinoma. The hospital mortality rate was 18 per cent and the morbidity rate 43 per cent. Mortality was not influenced by the extent of the tumour. Survival rates at 1,2 and 3 years were 28, 9 and 4 per cent, respectively. The median survival time was 17 months for localized tumours, 10 months for those that had invaded surrounding tissues, 6 months in the presence of lymph node involvement and 3 months with distant metastasis. The quality of survival was good for most patients with localized tumours but poor for those with parenchymal metastasis, in whom palliation was transient for 85 per cent and effective for less than half of their survival time for 60 per cent. These results suggest that patients with distant metastasis but without impending duodenal obstruction should undergo palliation by endoscopic or percutaneous routes while those with less advanced disease or with duodenal involvement remain candidates for surgical bypass.

Elective hepatic resection in the elderly.

This retrospective review assessed the safety and validity of elective liver resection in patients older than 64 years of age. In all, 293 patients underwent elective liver resection over a 23-year period (1967-1990). Fifty-two patients (18 per cent) were older than 64 (maximum 84, mean 70.4) years and all but four of these did not have cirrhosis. In this older subgroup, indications for resection were liver metastases in 30 patients, primary malignancy in 16, benign tumours in five and multiple abscesses in one. There were 21 major resections, with two deaths from hepatic failure, and 31 minor resections, with one death from cardiac failure (total mortality rate 6 per cent). During the same period, there were seven deaths after elective resections performed in 222 patients without cirrhosis who were younger than 64 years (P = 0.39). Mortality rate and duration of postoperative hospital stay were not related to the extent of liver resection nor to patients' grading according to the American Society of Anesthesiologists' criteria. Intraoperative blood loss was the only parameter found to influence mortality rate (P = 0.008) and duration of hospital stay (P = 0.04). Elective liver resection can be safely undertaken in elderly patients without cirrhosis, provided that intraoperative blood loss is minimized.

[Final evaluation of the randomized multicenter study SAKK 40/81: adjuvant portal chemotherapy of curatively resected colorectal cancer]. / Endauswertung der randomisierten Multizenter-Studie SAKK 40/81: Adjuvante portale Chemotherapie beim kurativ resezierten kolorektalen Karzinom.

Between 1981 and 1987, 533 patients from 9 institutions have been entered in a randomized trial to assess the value of adjuvant portal infusion (5-Fluorouracil, Mitomycin C) compared to radical surgery alone. Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group. Estimated 5-year disease-free survival was 52% and 61% respectively (hazard ratio 1:0.75; 95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the control and 69 in the infusion group (p = 0.048). Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate.

[Hepatic resections for metastases]. / Résections hépatiques pour métastases.

Between January 1981 and December 1990, 79 liver resections were performed for hepatic metastases in 73 patients. Eight of these patients had a repeat resection (2 patients had their first resection performed before 1981). This figure represented 35% of 228 liver resections performed during this period. Mean age was 56.5 years (23 to 81 years). There were 38 men and 35 women. Fifty-four resections were performed for colorectal metastases and 25 resections for secondaries of other origins. There were 45 major hepatectomies (57%), defined by the resection of at least 3 Couinaud segments, and 34 minor resections (less than three segments). In 12 patients, liver resection was associated with excision of the primary tumor. Complications were observed in 25 patients (32%), pulmonary complications being the most frequent. Five re-explorations were necessary: 3 for postoperative bleeding, one for an abdominal abscess and one for intestinal obstruction. Mean postoperative stay was 18 days. There was no mortality for the first liver resections in 71 patients. One death was encountered among the second resections in 8 patients, with a global mortality of 1.3%. Follow-up was obtained for all patients but one (lost to follow-up at 5 years). Actuarial survival for the 50 patients operated on for colorectal secondaries was 98% at 6 months, 83% at 1 year, 46% at 2 years, 24% at 3 years and 15% at 5 years. In non-colorectal secondaries, the survival depended on the nature of the primary tumor but was very different from one patient to another.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of high-dose verapamil on systolic and diastolic cardiac function of non-cardiological patients and review of the literature]. / Effet du vérapamil oral à forte dose sur la fonction cardiaque systolique et diastolique de patients non cardiologiques et revue de la littérature.

We studied the effects of high doses of oral verapamil (480 mg daily) in a group of 28 patients undergoing intravenous drug therapy for terminal digestive tumor. One additional patient was prematurely withdrawn from the study due to the occurrence of second degree atrioventricular block, which regressed after the interruption of verapamil. Gated radionuclide angiocardiography was performed before and after treatment (mean duration 2 days). Verapamil induced a significant reduction of blood pressure and heart rate (132 +/- 19 mm Hg vs 124 +/- 18 mm Hg, p = 0.005 for systolic blood pressure, 80 +/- 13 mm Hg vs 76 +/- 9 mm Hg, p = 0.04 for diastolic blood pressure and 81 +/- 17 bpm vs 77 +/- 13 bpm, p = 0.02 for heart rate). Left ventricular ejection fraction and peak filling rate were not impaired (65 +/- 7% vs 64 +/- 7%, p = NS and 2.52 +/- 0.65 EDV/s vs 2.42 +/- 0.51 EDV/s, p = NS), while peak ejection rate decreased slightly (2.96 +/- 0.72 EDV/s vs 2.72 +/- 0.50 EDV/s, p = 0.01). Conversely, there was significant alteration of right ventricular systolic indexes (50 +/- 7% vs 46 +/- 7%, p = 0.01 for the ejection fraction and 2.06 +/- 0.53 EDV/s vs 1.88 +/- 0.44 EDV/s, p = 0.008 for the peak ejection rate), without change in the peak filling rate (1.54 +/- 0.46 EDV/s vs 1.46 +/- 0.46 EDV/s, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Hematological toxicity of adjuvant portal liver infusion with fluorouracil, mitomycin and heparin.

Adjuvant perioperative liver infusion chemotherapy with fluorouracil, mitomycin and heparin caused mild but significant myelosuppression in the first two postoperative weeks. This was associated with a slightly increased bleeding tendency. Mortality was not increased. Future trials might combine chemotherapy with hematopoietic growth factors in order to minimize myelosuppression.

Pylorus-preserving duodenopancreatectomy: long-term complications and comparison with the Whipple procedure.

We have performed 33 pylorus-preserving duodenopancreatectomies. Twenty patients presented with severe chronic pancreatitis and 13 with periampullary adenocarcinoma. We have no postoperative mortality and a 24% rate of morbidity. Complications include anastomotic leaks (2), surgical bleeding (1), anastomotic ulceration (1), and others (4). We have complete follow-up for all cases. In the tumor group, 8 (62%) patients are alive with a mean survival time of 20 months (range: 2-46). In the pancreatitis series, all patients are alive after a mean of 34 months (range: 4-66). We have observed 5 cases (15%) of anastomotic ulcerations responsible for stenosis (2) and acute perforation with peritonitis (2) occurring after a mean interval of 18 months. Four cases have been confirmed histologically after resection. The short- and long-term beneficial effects of the pylorus-preserving operation on patient well-being and nutritional status were confirmed and compared with the results achieved after a Whipple procedure performed in a series of 18 consecutive patients.