Homocamptothecin, an E-ring-modified camptothecin, exerts more potent antiproliferative activity than other topoisomerase I inhibitors in human colon cancers obtained from surgery and maintained in vitro under histotypical culture conditions.

Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e., E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al., Cancer Res., 59: 2939-2943, 1999). Forty-three human colon cancers were obtained from surgical resection and maintained under organotypical culture conditions for 48 h. Cell proliferation was assessed in these ex vivo tumor tissue cultures by tritiated thymidine autoradiography. As a validation of the methodology, we first analyzed in our model the antiproliferative activity of two clinically active topoisomerase II (Topo II) inhibitors, Adriamycin and etoposide, which are not active for colon cancers; and three Topo I inhibitors, camptothecin (CPT) and two clinically active compounds (especially for colon cancers), i.e., topotecan and the active metabolite of irinothecan, SN-38. We then compared the antiproliferative activity of CPT, topotecan, and SN-38 against those of two investigational E-ring-modified camptothecins, i.e., BN80245 and BN80915. Three concentrations (1, 10, and 100 nM) were studied for each compound. The results indicate that the three Topo I inhibitors used as references, i.e., CPT, irinothecan, and SN-38, were much more active than the two Topo II inhibitors, i.e., Adriamycin and etoposide, with SN-38 being the most efficient. The two investigational compounds BN80245 and BN80915 exerted higher antiproliferative activity than the three anti-Topo I reference compounds, with the highest activity observed for BN80915.

Metastatic involvement of ceco-appendicular segment: a diagnosis of right lower quadrant abdominal pain in patient receiving chemotherapy.

Metastases are a common feature during the evolution of breast cancer. However, gastrointestinal metastases, and especially ceco-appendicular ones, are very rare. Melanoma however frequently metastasize in the gastrointestinal tract. Ceco-appendicular metastases do not display any specific signs in cancerous patients. These rare metastases must be considered in the diagnosis of right lower quadrant pain in cancerous patients. The main differential diagnosis includes neutropenic enterocolitis, acute appendicitis, malignant intestinal obstruction and perforation of the bowel. The morbidity of gastrointestinal complications in patients with metastatic cancer receiving chemotherapy is significant and surgery is often the only chance of survival. The major clinical decision is whether or not to operate.

Gastro-oesophageal and bile reflux--simultaneous quantitative assessment with gastric and gallbladder emptying evaluation: clinical applicability of a new computerized gammagraphic method.

The aim of this study was to develop a new computerized gammagraphic method to evaluate gastrooesophageal (GER), bileo-oesophageal (BER) and bileogastric reflux (BGR) simultaneously with gastric and gallbladder emptying: a long duration (60 min) and a dual energy detection (113Inm-sulphur colloid and 99Tcm-HIDA) test of the different refluxes during slow gastric emptying of an enteric feeding liquid meal. Forty patients with oesophagitis and 18 normal volunteers were evaluated. Good reproducibility of all the quantified parameters was found with r Spearman between 0.75 (P < 0.05) and 1.0 (P < 0.001). Patients with oesophagitis have a tendency for slower gastric emptying patterns (gastric emptying T1/2, GT1/2 P < 0.05). The calculated specificity for gallbladder emptying parameters was 77.8% for the gallbladder T1/2 BT1/2) and 94.4% for gallbladder residue at 60 min (BR60). The calculated accuracy for the GER index was 90%. The predictability for positive values was 95%, owing to a 90% sensitivity and 89% specificity. The predictability for negative values was 80%. The mean GER index in oesophagitis was greater than in controls (P < 0.001). The calculated specificity for BGR was 94.4% and reflux was detected in 12 out of 40 patients. The calculated specificity for BER was 83.3% for a '+' index and 94.4% for a '++' BER index. In 14 patients a positive BER index has been determined ('+' in three and '++' in 11 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between estrogen receptor concentration and clinical and histological factors: their relative prognostic importance after radical mastectomy for primary breast cancer.

After modified radical mastectomy, 490 primary breast cancer patients were followed for a median of 75 months. Bloom grade was measured in 340 patients and ER status in 341. Follow-up of these patients has yielded the following results: (a) The value of traditional indices has been reaffirmed. (Cox's multivariate analysis identified, in order of decreasing importance, the number of invaded lymph nodes, the initial tumor size and the histological grade. Other variables were found to be of lesser importance and were correlated with the three main indices.) (b) The value of ER status disappeared after more than 3 years of follow-up. (c) ER positive patients fared better after recurrence. This was interpreted as being a consequence of their responsiveness to hormonal treatment.

[Lymphedema after modified radical mastectomy as performed at the Bordet Institute. A report of 60 cases (author's transl)]. / Le lymphoedème du bras après mastectomie radicale modifiée, expérience de l'Institut Bordet. A propos de 60 cas observés.

Three hundred and fifteen patients who underwent a radical mastectomy between 1969 and 1976 were studied. Nineteen percent developed lymphedema of the upper limb. Ten percent were resistant to all forms of therapy while the pathology gradually subsided in 9%. The causes of lymphedema as well as the preventive and curative methods were statistically studied and compared with those in the literature. Several preventive measures are proposed, in particular, the modified radical mastectomy.

[Explorative laparotomy with splenectomy in malignant lymphomas (author's transl)]. / La laparotomie exploratrice avec splénectomie dans les lymphomes malins

Between January 1, 1971 and February 1, 1974, 31 patients have undergone laparotomy for staging of a malignant lymphoma, Hobgkin or not. Laparotomy consisted in a median incision, above and below the umbilicus allowing multiple node biopsies, hepatic and splenic biopsies. In 17 cases out of 31, i.e. 54% preoperative clinical stage was changed by this explorative pathology. Among untreated cases, the most frequent change was from a low to a higher stage and inversely, among treated cases, most frequent changes were from plus towards minus. Postoperative mortality is nill and morbidity 5/31, i.e. 16%. This technique yields better definition of the degree of lymphoma extension, in particular intra-abdominal, and thus allows better treatment. The author thus commends explorative laparotomy with splenectomy for all malignant lymphomas, Hodgkin or not, except for stage IV, proven biopsy.