Forssman-like antibody levels in sera of patients with lung cancer.

Sera of normal individuals or patients with lung cancer were assayed for Forssman-like antibody by a quantitative and specific method using ethylenediaminetetraacetate-containing buffer to inactivate complement in the test serum. It was shown that although Forssman-like antibody levels were distributed widely, (a) the levels of young (20 to 45 years of age) normal subjects of Blood Groups A and AB were lower than those of Blood Groups O and B, (b) the levels of old (60 to 80 years of age) normal subjects were lower than those of young normal subjects of Blood Groups O and B, and (c) the levels of old lung cancer patients were lower when compared to age-matched normal individuals of their blood group.

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.

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 operative treatment of gastrointestinal tract tumors in patients over 80 years of age.

Between 1981 and 1986, 140 patients over 80 years of age were operated on for a gastrointestinal tract tumor in our service. There were 24 gastric, one small-bowel, 91 colonic, and 24 rectal cancers. Only 40% of the patients were preoperatively free of any systemic disorder other than tumor. We performed surgical procedures with a curative intent for 90 (64%) of them. Our mean overall postoperative mortality was 17%, but this rate could be decreased by performing elective operations on well-prepared patients. Over 80% of the deaths were related to systemic organ failures. Eighty-three percent of the survivors (96 patients) returned to their homes; 82% (94 patients) had normal activities for their age. The actuarial survival curve showed a 50% survival rate at three years, all tumoral stages included. These results support the view that surgery is a safe, valid option in the face of gastrointestinal tract tumors in the elderly.

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.

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.

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.

Cobalt-57 bleomycin scanning for lung cancer detection: a prospective study in thoracic surgery.

Patients displaying an abnormal chest X-ray, in some cases, cause a difficult diagnostic problem. A differential diagnosis between benign and malignant lesions is important to determine the choice of treatment i.e. whether or not to perform a thoracotomy. In a prospective study, we have examined the role of 57Co-bleomycin scanning for prethoracotomy assessment of 60 patients with a high clinical probability of lung cancer. For these patients, a sensitivity of 89%, a specificity of 84% and an accuracy of 88% were found. However, as a consequence of the six false-negative scans (two in-situ carcinomas and four stage I carcinomas), bleomycin scanning cannot be regarded as adequate for obviating thoracotomy in patients with a high clinical probability of lung cancer but a negative scan. Nevertheless, the technique is useful for the assessment of tumour size and for the detection of hilar, mediastinal and extra-thoracic metastases, with consequences for TNM staging. It has been found that the tumour dimension correlates well with the actual anatomo-pathologic size determined after surgical examination (r2 = 0.65 and p less than 0.01). Therefore, with an accuracy around 90% for the diagnosis of lung cancer, 57Co-bleomycin scanning offers a major tool for use in clinical investigation.

Single photon emission computed tomography study of human cancer: utilization of 57Co-labelled bleomycin.

The sensitivity and specificity of single photon emission tomography with 57Co-labelled bleomycin (57Co-BLM) for the detection of cancer was determined from a prospective study involving a large group of patients selected to investigate roentgenographic abnormalities. Eighty-four of the 104 patients studied had malignant disease, of whom 76 had a positive scintigram. Eighteen of the 20 patients with benign disorders had a negative scintigram. The sensitivity and specificity was therefore 90.5 and 90% respectively. For the subset of patients who underwent investigation below the diaphragm, the sensitivity was 85.7%, while for investigation above the diaphragm, it reached 95.2% (this excluded reconstructions on the bladder level, because it produced large artifacts). This study leads to the conclusion that SPECT can be used specifically to investigate unidentified X-ray abnormality and diagnose malignancy using 57Co-BLM. In addition, we propose further investigation to evaluate the usefulness of this method in staging cancer.

[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.

[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)

[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.

[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.

Mammography in symptomatic women 50 years of age and under, and those over 50.

Our experience with the use of mammography as a diagnostic aid in symptomatic women with breast complaints has been presented. One-third of all cancers were found in women 50 years of age and under. The detection of cancer by mammography in the younger age group was similar to that experienced in the older age group. Radiation exposure by mammography has diminished markedly during the last 15 years--only one-third to one rad per exposure with modern technique. Recent hysterical criticism of the use of mammography in women under 50 years of age is unwarranted in the light of current findings. This diagnostic modality should be utilized when indicated in all age groups over 30. It is probable that screening clinics should include all women over 35 years of age.

[Cancer surgery in patients over 80 years old]. / La chirurgie dans le cancer chez les patients de plus de 80 ans.

Malignant tumors are a frequent problem in gerontologic medicine; moreover, the number of geriatric patients is increasing. Surgical treatment is often proposed for solid tumors, even in patients over 80 years of age. 183 cases observed over the last 15 years in the Digestive and Thoracic Clinics of the University Hospital, Geneva, are reviewed. The affected organs were, in order of frequency, 1. large bowel, 2. breast, 3. stomach, and, more rarely, biliary tract, pancreas, esophagus and liver. Postoperative survival was satisfactory in this series. Analysis by organ shows that, in the case of the large bowel, one-stage resection-anastomosis provides the best results. For the breast, the classic procedures under general anesthesia are recommended. For the stomach, resection of the tumor prolongs survival. Postoperative mortality within 30 days is not increased by this type of intervention. Classification of evaluation of operative risk, as proposed by the American Society of Anesthesiologists, corresponds favourably with the postoperative mortality rate. For nearly 60% of our patients the quality of life is the same postoperatively as before. In this group, 78% have a Karnofsky index of 100%. It can therefore be stated that surgery for solid tumors is well tolerated by geriatric patients.

Rotter's node metastases. Therapeutic and prognostic considerations in early breast carcinoma.

In 500 consecutive modified radical mastectomies (MRM) performed for clinically early (T1 N0) breast carcinomas between 1975 and 1982, the interpectoral lymph nodes (IPN) were separately sampled at the end of the operative procedure. Among the patients consistently sampled (1979-1982), lymph nodes were found in 73%. Interpectoral lymph node metastases were found in 2.6% of all patients, 3% of patients with infiltrating cancers, and 4% of patients sampled. A total of 8.2% of axillary node positive and 0.5% of axillary node negative patients had IPN disease. Among the 13 patients with positive IPN, there were no differences in tumor size or location from the entire group. The two patients whose only nodal metastases were to the IPN are currently disease-free without having received systemic adjuvant therapy. These data suggest that for early breast cancers treated by MRM, routine excision of the IPN is of potential therapeutic or prognostic benefit in very few cases. However, as MRM is increasingly applied to patients with more locally advanced disease (T2-3, N1b-N2), metastases in unexcised IPN may become a more significant source of local or systemic treatment failure.

[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)

[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.

[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.