Relationship between systemic 5-FU passage and response in colorectal cancer patients treated with intrahepatic chemotherapy.

The study described herein was conducted to analyze the relationship between tumor exposure to 5-FU and clinical response. Six patients were placed on continuous 5-day intrahepatic 5-FU chemotherapy for colorectal cancer metastasized to the liver. The starting dose was 600-800 mg/m2 per day; cycles were repeated at 4-week intervals. The 5-FU dose was increased by 250 mg/day at each cycle. All six patients received 3 or more cycles, for a total of 37 cycles. Response was evaluated after each cycle by ultrasonography or computed tomography (CT). Pharmacokinetic data revealed a high individual cycle-to-cycle variability for all six patients in the 5-FU area under the curve (AUC day 1 to day 5) corrected for the dose. These variations in drug biodisposition, reflecting hepatic 5-FU uptake, were significantly related to measurable modifications in the tumor mass in 71% of cycles. The correlation between the reduction in local drug exposure and tumor regrowth was better than that between the increase in local drug exposure and tumor reduction. These findings constitute an original illustration in humans of the experimental concept of the drug exposure/tumor response relationship for 5-FU.

Labeling index and labeling distribution in the colonic crypts: a contribution to definition of patients at high risk for colorectal cancer.

The labeling index (LI), representing the percentage of S-phase cells, was measured in the healthy colorectal mucosa of subjects without a personal or familial history of neoplasm as well as in persons with a positive history, and was compared to the LI in benign or malignant lesions in a total of 128 subjects. In the healthy mucosa, LI was lowest in control subjects; it rose progressively in patients with a personal history of adenoma, patients with non colorectal cancer, and colorectal cancer patients respectively. There was a significant increase in LI from healthy mucosa to adenoma to carcinoma. The pattern of labeling in the crypts was studied in 56 subjects with different familial and personal histories. Limitation of labeling to the deepest part of the crypts was observed in control subjects and to a lesser extent in the healthy mucosa of patients with adenoma. An upward shift of the proliferative zone was observed in patients with a personal or familial history of cancer; adenomatous lesions had an inverse labeling distribution: labeling decreased from the luminal aspect towards the deep segments. High LI values and a shift of the proliferative zone towards the surface of the crypt may identify individuals at high risk for cancer of the colon and rectum.

Colonic and rectal lymphomas. A report of six cases and review of the literature.

In connection with six cases of colorectal lymphomas, including five cases of non-Hodgkin lymphomas (3 primary, 2 secondary), and one case of Hodgkin's disease, the authors review the literature concerning the general features and radiological aspects of these pathologies. The radiological signs observed during barium enemas for non-Hodgkin lymphomas are as follows: a small nodular pattern, frequently with multiple lesions (45.7% of cases), a diffuse or infiltrating pattern (25.4%), a filling defect (22.9%), endo- and exo-luminal images (17.8%), ulcerating patterns (3.4%) and a pure mesenteric form (0.8%). Thus, associated radiological forms are present in 16% of cases. The preferential site is the caecum (52.5% of cases), followed by the rectum (21.2%). Colonic or rectal involvement by Hodgkin's disease is extremely rare. From a radiological viewpoint, the most frequently described pattern in the literature is an infiltrating lesion which may or may not cause stenosis; the most frequent site is the caecum.

A radiologic study of chronic radiation-induced injuries of the small intestine and colon.

On the basis of 144 radiation-induced intestinal and colorectal lesions seen in 109 patients, the authors review the radiologic aspects associated with such affections. Two points are emphasized: (1) the chronic and still active nature of radiation-induced injury which can explain the appearance of lesions more than 10 years after irradiation, and (2) the locoregional nature of the affection which warrants systematic exploration of the urinary tract by intravenous pyelography in addition to radiologic and endoscopic investigation of the digestive tract. The authors also advise an echography and/or CT scan to detect any neoplastic recurrence.

Assessment of nutritional proteins during the parenteral nutrition of cancer patients.

Albumin, prealbumin, retinol-binding protein, and transferrin were all measured on the sera of 39 cancer patients before and during parenteral nutrition (PN). At the outset of PN, the concentrations of all of these proteins were low, as compared to reference values, and thus quantitatively reflected the degree of malnutrition. Prealbumin proved to be the most interesting parameter during PN: (1) during an initial period it rapidly reflects the nutritional input, and (2) after two weeks of PN it allows differentiation of patients whose prealbumin level rises regularly during PN and will survive from those patients whose prealbumin level drops after the initial period and will die during or within the month following PN. Prealbumin thus offers a means for biochemical monitoring of PN as well as having a prognostic value.

[Treatment of cancer of the anal canal with combination radiochemotherapy: apropos of 12 cases]. / Traitement des cancers du canal anal par association radio-chimiothérapie: à propos de 12 cas.

We present 12 patients (3 male, 9 female) aged from 53-88 years with squamous cell cancer of the anal canal treated with combined radiotherapy-chemotherapy (5 FU-mitomycin C); the distribution of the tumours was 2 T4, 6 T3, 3 T2, 1 T1). In 11 patients evaluated, complete remission was obtained in 8 with partial remission in 2 others. In spite of this good result with combined treatment, 4 patients had a recurrence between 9 and 26 months. Five patients survived and 2 died without disease (16-38 month), 3 patients died and one survived with disease. The small series confirms the efficacy of this combination which treated bulky tumours (T3-T4). It is necessary however to compare these results with radiation alone in a randomised trial.

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients.

Systemic delivery of mitomycin C (MMC) was studied in 6 patients administered microencapsulated MMC (MMC-mc) by an intra-arterial route (IA): 3 IA liver infusions, 3 IA pelvic infusions. Pharmacokinetic data revealed a lower blood MMC availability (peak plasma levels, AUC 0-4 hours) for the pelvis than for the liver; this was attributed to differences in the blood flow infusion rates at these two sites of administration. Direct comparison of systemic MMC exposure was possible for one patient, who received both IA liver MMC (10 mg in standard form, which served as the control) and IA liver MMC-mc (20 mg the day after). The 65% reduction in MMC-mc bioavailability observed for this patient indicates a quantitative local improvement in exposure to the drug and correlates well with the low incidence of systemic side effects noted in preliminary clinical studies.

[Critical study of the methods available for detecting hepatic metastases (author's transl)]. / Etude critique des différentes méthodes de détection des métastases hépatiques.

Based on a review of data in the published literature, and the results of their personal experience in the Antoine-Lacassagne Centre in Nice, the authors discuss the different techniques employed for the detection of hepatic metastases: biological tests, liver needle biopsy, laparoscopy, laparotomy, hepatic angiography, scintigraphy, ultrasonography, and computed tomography. In 90 p. cent of cases liver biological tests and ultrasonography were sufficient to eliminate or confirm the presence of hepatic metastases. When there is no correlation between the results of the different non-traumatic techniques, one is justified in proposing a liver biopsy under laparoscopy.

[Comparative study of ultrasonography and scintigraphy in liver metastases detection (author's transl)]. / Etude comparative de l'échographie et de la scintigraphie dans la détection des métastases hépatiques.

The sensitivity and specificity of ultrasonography and scintigraphy for detecting the presence of liver metastases were compared in 250 patients with cancer. In the 80 cases with metastases, the sensitivity of ultrasonography was 95%, that of scintigraphy being 75%. In 170 cases without metastases the specificity of ultrasonography was 96%, that of scintigraphy being 92%. These results, confirmed by reports in the published literature, show that ultrasonography should be the first morphological-detecting examination for suspected hepatic metastases, with scintigraphy as a second option.

[Adenocarcinoma of the small intestine. Current state of diagnosis and treatment. A study of 27 cases and a review of the literature]. / L'adénocarcinome de l'intestin grêle. Etat actuel du diagnostic et du traitement. Etude de 27 cas et revue de la littérature.

On the basis of 27 personal cases of adenocarcinoma of the intestine and a review of the literature, the authors discuss present-day knowledge about this pathology from both radiologic and therapeutic viewpoints. This study, which excludes papillary tumors, reveals that, on a para-clinical level, barium follow-through examinations allow correct diagnosis in 85% of cases. Arteriography does not provide any special data, and more recent techniques such as ultrasound and C.T. do not appear suited for use in initial investigations. From a therapeutic standpoint, surgery is the only effective solution, but long-term survival had not increased for forty years. This rare form of cancer, with an especially insidious clinical course, has thus not benefited from recently introduced diagnostic and therapeutic technics.

[The liver masses in ultrasonography. Report on 400 cases (author's transl)]. / Les masses hépatiques en échographie. A propos de 400 cas.

On the basis of 400 cases of liver masses, the authors have drawn conclusions that can be used to orient etiological investigations: --one or more well demarcated transsonic formations always correspond to a cystic etiology: --a hyperechoic metastatic liver points towards a primary cancer of the digestive tract whereas a hypoechoic metastatic liver is only rarely caused by such a cancer. The authors also propose a strategy for the exploration and surveillance of isolated hyperechoic or transsonic nodules of no more than 3 cm.

[Critical evaluation of non-biological complementary examinations of the biliary tract before deciding on therapy (author's transl)]. / Etude critique des explorations complémentaires non biologiques des voies biliaires avant la décision thérapeutique.

A critical evaluation of non-biological complementary examinations of the biliary tract was conducted to assess their value when deciding on therapy. The published literature was reviewed, and the sensitivity and specificity of the different methods presented, emphasis being placed on the primary investigations of ultrasonography and oral and intravenous biligraphy. Secondary exploratory procedures (transparietal cholangiography, retrograde endoscopy with cholangiography and pancreatography, scintigraphy, gallbladder infusion parietography, scanography, and arteriography) are defined and their value discussed. Published data suggest that ultrasonography should be the initial investigation, this often being sufficient to enable suitable therapy to be chosen. Only approximately 5 p. cent of patients are unable to benefit from gallbladder exploration, and these require conventional radiological examinations before deciding on therapy.

[Interventional radiology in chemotherapy. Percutaneous arterial route and and embolization with microspheres]. / Radiologie interventionnelle en chimiothérapie. Voie artérielle percutanée et embolisation de microsphères.

The authors present their experience with interventional radiological techniques employed for chemotherapy: 205 intra-arterial chemotherapy (IAC) cycles were administered to 67 patients (lesion sites were: liver 20, pelvis 35, unknown 12). Catheters were left in place for 5 days in 89% of cases. The positions of the end of the catheter was checked by CT scan, with concomitant arterial opacification in the case of pelvic pathologies; this allowed evaluation of the tumor volume treated. Serious radiological complications of IAC included: 2 surgical thrombectomies and 2 surgical removals of broken catheters (2% complication rate for IAC). 15 embolizations with microcapsules of mitomycin were performed for 11 patients, using the technique of Kato. Venous blood samples revealed the persistence of mitomycinemia for up to four hours. three instances of pain were noted in the 24 hours following embolization. These two techniques have a low rate of serious complications; the therapeutic efficacy observed in certain cases warrants the use of these methods for cancers impossible to treat by radical procedures.

[Adriamycin in low weekly doses. Latest therapy of advanced cancer of the breast]. / L'adriamycine à faible dose hebdomadaire. Dernière thérapeutique du cancer du sein avancé.

Thirty-four patients with heavily pretreated advanced breast cancer received adriamycin in weekly doses of 12 mg/m2. Twenty-two patients (18 assessable) had a performance status greater than or equal to 3 (WHO scale). There were 5 (28%) partial responses, 7 (39%) minimal responses, 3 cases (17%) with no change and 3 (17%) with progressive disease; the mean duration of response was superior to 9 months (range: 3-12 months). In the remaining 12 patients, who had resisted a previous multidrug regimen containing adriamycin, there were 3 (25%) partial responses, 2 (17%) minimal responses, 4 cases (33%) with no change and 3 (25%) with progressive disease; the mean duration of response was superior to 5 months (range: 3-11 months). More than 600 weekly injections were administered with only minor blood and digestive tract toxicities. No alopecia was recorded. The total cumulative dose of adriamycin was superior to 900 mg/m2 in 8 patients; none had clinically evident cardiac toxicity. Adriamycin extravasation with subsequent tissue necrosis occurred on 10 occasions due to the frequency of administration; this problem was solved by the systematic installation of central venous catheters.

Secretory pattern and pathological study of the pancreas of steroid-treated rats.

Rat were given 2.5 mg/kg/day prednisolone in drinking water during 1.5 to 12.5 months and an equal group of matched controls received only water. A pathological study of the pancreas and a physiological study of exocrine pancreatic secretion have been done. The most significant pathological effects at 1.5-12.5 months of steroids are dilatation of acini, flattening of duct epithelium, and the presence of protein plugs in the ducts. The most significant functional modifications at 9-11 months of treatment are increased concentrations and output of proteins both in basal and stimulated pancreatic secretion of steroid-treated rats. This is very similar to the results observed by our group in alcohol-induced pancreatitis. It is assumed that the hyperconcentration could be at least partly responsible for precipitation of proteins and the precipitate formation for the lesions. For the large group of acute or chronic pancreatic lesions characterized by the formation of protein plugs in the ducts, the term catarrhal pancreatitis is proposed.

[Interaction of dimethyl prostaglandin E2 and ethanol on the pancreatic secretion of the rat]. / Interaction de la dimethyl prostaglandine E2 et de l'ethanol sur la secretion pancreatique du rat.

We have studied the action of 16,16-dimethyl prostaglandin E2 methyl ester (DiMePGE2) on pancreatic secretion in the unanesthetized rat with pancreatic and duodenal fistulae. DiMePGE2 inhibited volume, protein secretion and bicarbonate output. The inhibition of protein concentration is dose related (ED50 = 5.35 microgram/rat). DiMePGE2 was effective by the intraduodenal, intravenous, and intraperitoneal routes. Intraduodenal infusion of ethanol alone (2 mL 16% (v/v) in 1 h) strongly increased protein secretion (concentration, +30%; output, +69%) When 4 microgram DiMePGE2 was injected intraperitoneally just before the ethanol infusion, the secretory effect of ethanol disappeared and the inhibition was similar to that observed with DiMePGE2 alone.

Clinico-pathological conditions associated with pancreas divisum.

Nonfusion of the pancreatic ducts (pancreas divisum) was diagnosed in 41 of 812 patients in whom ERCP provided a definite diagnosis (5.04% of cases). Pancreas divisum was significantly associated with diseases of the pancreas. Chronic pancreatitis was less frequently observed in cases of pancreas divisum whereas acute pancreatitis, especially acute recurrent pancreatitis, was statistically more frequently seen in patients in whom the anomaly was present. These results support the hypothesis that pancreas divisum favours the development of acute pancreatitis.

Reevaluation of alkaline phosphatase measurement during Hodgkin's disease by electrophoretic isoenzyme separation.

Electrophoretic isoenzyme separation provides much more precise information than measurement of alkaline phosphatases (AP). Use of this technique for 83 patients with Hodgkin's disease revealed that the presence of the alpha 1 fraction (alpha 1 AP) was very significantly correlated with the stage of disease extension (P less than 0.01) and above all with the presence of general symptoms (P less than 0.001). Repeat measurements performed during patient follow-up demonstrated a close association between presence of alpha 1 AP and existence of progressive disease. While the mechanism of appearance of this abnormal alpha 1 AP fraction is not linked to Hodgkin-specific liver lesions, this test provides much more interesting data than classical measurement of total alkaline phosphatases (TAP).