Neodymium-yttrium aluminium garnet laser destruction of nonsensitized and hematoporphyrin derivative-sensitized tumors.

The injection of hematoporphyrin derivative (5 mg/kg i.v.) followed 24 hr later by a neodymium-yttrium aluminium garnet laser irradiation shows the destruction of CX1 tumors grafted on nude mice. This acidophilic necrosis occurred with a significantly increased frequency in tumors treated by hematoporphyrin derivative injection and irradiated with the neodymium-yttrium aluminium garnet laser as compared with noninjected but irradiated tumors or with injected tumors irradiated with sunlight. On the basis of our data, it seems difficult to maintain the hypothesis of singlet oxygen production as the only mechanism of the phenomenon. Further studies will be necessary to explain the necrosis that we observed.

Experimental aspects of in vitro and in vivo photochemotherapy.

The selectivity of in vitro photodynamic reactions and the in vivo effects induced by PRT, whether the irradiation is applied interstitially or externally, still remains unclear. In vitro studies were performed using leukemic cell lines and syngeneic normal hemopoietic progenitors. For these, cells incubated with hematoporphyrin derivative (HPD) and non-incubated cells were irradiated with an argon laser. Data were obtained as the count of cell colonies found after a 7-day incubation period on semi-solid collagen gel medium. In vivo studies employed the HT 29 tumor model grafted into nude mice. Both animals injected with HPD and non-infected controls were irradiated with a dye laser pumped by an argon laser (Coherent) using a 400 micron optic fiber located either at a distance of 65 mm from the skin or inserted into the tumor. The temperature increase occurring during PRT was measured using non-absorbing thermocouples. In vitro, after HPD treatment and argon irradiation leukemic cells showed a greater phototoxicity (greater than 2 log10) than did the normal cells (0.25 log10). In vivo, when the heat rise is very similar (less than 4 degrees C) in both the tissues irradiated externally and those irradiated interstitially after HPD injection, histological examination of these did not reveal any quantitative differences (90% of tumor mass). These results are discussed.

Influence of hematoporphyrin derivative concentration, incubation time, temperature during incubation and laser dose fractionation on photosensitivity of normal hemopoietic progenitors or leukemic cells.

Photodynamic therapy represents a new approach for the local control of cancers. It has recently been claimed that photodynamic therapy mediated by hematoporphyrin derivative (HPD) is selectively more efficient for killing leukemic cells than normal progenitors. To improve this effect, we studied the influence of hematoporphyrin dose, temperature during incubation and/or treatment, hematoporphyrin derivative incubation time, and fractionation of the argon laser light (488-514 nm) used for hematoporphyrin stimulation. Plating efficiency calculated after a 7-day period of growth on collagen gel medium showed a dose-dependent phototoxicity of HPD reaching 0.01% for normal hemopoietic progenitors and 0.001% for leukemic cells (dose = 12.5 micrograms/ml). The 10:1 ratio of normal hemopoietic progenitors to leukemic cells was also found to be the same or increased when temperature was 37 degrees C during incubation and 4 degrees C during laser irradiation. Similar results were also found when incubation time was varied from 75-120 min, or when laser irradiation dose was fractionated into 2 or 3 periods. The ratio of normal progenitors to leukemic cells reached 100:1 when 75 J/cm2 were fractionated into 3 periods after an incubation time of 120 min with 10 micrograms/ml HPD. Selectivity in photodynamic treatment seems to occur between normal hemopoietic progenitors and leukemic cells. The mechanism of this selectivity remains unclear, but experiments with the fractionated irradiation dose suggest that as in radiotherapy, better potentially lethal damage repair in normal cells could be a factor for selectivity in photodynamic therapy. Our results obtained with leukemic cells are fully in agreement with data in the literature concerning similar experimental models.

Endoscopic photodynamic therapy with haematoporphyrin derivative in gastroenterology.

Endoscopic photodynamic therapy (PDT) with haematoporphyrin derivative was used in the primary treatment of 69 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups: 31 with oesophageal squamous cell carcinoma, 17 with adenocarcinoma of the stomach or lower third of the oesophagus and 21 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg haematoporphyrin derivative per kilogram of body weight, lesions were irradiated using an argon dye laser (632 nm). During a follow-up period averaging 20 months (27.9 months for 35 surviving patients), complete local tumour destruction and negative histology were observed in 32 out of 69 cases. Flow-cytometric analysis of DNA content before and after PDT suggests that a clonal selection occurs in some cases of treatment failure. The results of this open pilot study suggest the potential efficacy of PDT as a curative treatment for selected cases of inoperable gastrointestinal cancers.

Thermography as a predictive tool for laser treatment of port-wine stains.

The argon laser, which has been proven both useful and safe for port-wine stain therapy, interacts with the hemoglobin of the vessels. In a percentage of cases, this treatment is still inefficient, and there is a lack of correlation between these bad results and clinical or histologic criteria. Thermography, which explores the vascularization of the port-wine stain, leads us to consider port-wine stains from a physical point of view. This very simple test shows no correlation with the clinical parameters of port-wine stain but is closely related to the results obtained with laser therapy. It seems to be a good criterion to estimate the argon laser treatment prognosis.

[Prevention of recurrent hemorrhage in patients with cirrhosis. Results of a controlled trial of propranolol versus endoscopic sclerotherapy]. / Prévention des récidives hémorragiques chez des malades atteints de cirrhose. Résultats d'une étude contrôlée comparant propranolol et sclérose endoscopique.

Between July 1984 and March 1986, we conducted a prospective randomized trial comparing propranolol and endoscopic sclerotherapy in the prevention of recurrent variceal hemorrhage in a group of non selected alcoholic cirrhotics. Seventy-six patients with variceal hemorrhage were randomized to receive propranolol (P) (34 patients), or sclerotherapy (S) (42 patients) approximately 12 days after initial bleeding. The 2 groups were similar as concern age, sex, etiology of cirrhosis, severity of liver failure, the number of previous hemorrhages, and the severity of initial hemorrhage. No side effects were observed in the P group; 20 patients (48 percent) in the group S had at least one side effect although minor. After an average follow-up of 36 months, 18 patients in group P (53 percent) and 23 in group S (55 percent) had hemorrhagic recurrence. Rebleeding occurred from other sources than esophageal varices in 5 patients, in the group S only. Five patients in group P and 8 patients in group S died of rebleeding. During the follow-up period, 8 patients in group P (23 percent) and 13 patients in group S (31 percent) died. No significant difference could be demonstrated between the 2 groups as regards the percentages of patients without variceal rebleeding or survival, calculated according to the Kaplan Meier method. In conclusion, in this trial, no significant difference could be demonstrated between propranolol and endoscopic sclerosis in the prevention of recurrent variceal hemorrhage in alcoholic cirrhotic patients.

[Hormone immunocytochemical studies of 46 endocrine tumors of the pancreas in 24 patients]. / Etudes immunocytochimiques hormonales de quarante-six tumeurs endocrines du pancréas chez 24 malades.

The aim of this retrospective study was to correlate the results of hormonal immunocytochemistry of 46 endocrine tumors to the corresponding clinical syndromes in 24 patients. They were divided as following: 14 cases of insulinoma, 3 cases of Zollinger-Ellison syndrome, 1 case of glucagonoma, 1 case of carcinoid syndrome and 5 cases without any obvious endocrine manifestations. Each tumor was tested with anti-insulin, anti-glucagon, anti-pancreatic polypeptide, anti-vasoactive intestinal peptide, anti-gastrin immune sera according to the peroxidase-antiperoxidase method. The presence of insulin was proved in 13 of 14 cases of insulinomas and the presence of gastrin in 2 of 3 cases of Zollinger-Ellison syndrome. Among the 5 asymptomatic cases, a somatostatinoma and a vipoma were individualized. More than 50 p. 100 of the tumors showed plurihormonal secretion with one predominantly secreted hormone responsible for the clinical syndrome. This study demonstrated the diversity of the hormonal secretion by some tumors and their metastasis in the same patient. Malignant insulinomas correspond either to poorly secreting tumors or to plurihormonal tumors secreting gastrin and glucagon as well.

[The symptom index: progress in the analysis of esophageal pH metry]. / Le marqueur d'événements: un progrès dans l'interprétation de la pH-métrie oesophagienne.

Commercially available pH-monitoring systems include one or more event markers which should allow correlation between reflux episodes and symptoms. However, the clinical relevance of this feature has not yet been thoroughly investigated. In this prospective study, we attempted to establish whether the use of an event marker could improve the accuracy of intraesophageal pH-monitoring and if a correlation between symptoms, as detected by event markers and esophageal exposure to acid could be shown. One hundred seven patients were studied. Only 47 p. 100 used the event marker during 24 h pH-metry. There was no statistical significance in the incidence of gastroesophageal reflux (GER i.e. time spent below pH 4 greater than 4.2 p. 100), age and socioeconomic status between patients who used the marker and those who did not. A concordance index was calculated by dividing the number of reflux episodes associated with a marked event by the total number of marked events. In 50 p. 100 of the 16 patients who used the marker and had GER, the concordance index was greater than 75 p. 100. On the contrary, only 4 out of 35 patients without GER had a concordance index greater than 75 p. 100 (p less than 0.003). Finally, the index was less than 25 p. 100 in 4 patients with GER and in 22 without GER (p less than 0.02). The lowest pH reached within the esophagus was virtually identical during all the reflux episodes, regardless of marker pressing.(ABSTRACT TRUNCATED AT 250 WORDS)

[Campylobacter pylori and gastric mucosa: histological and bacteriological study and preliminary results of an epidemiological survey in the area of Nantes]. / "Campylobacter pylori" et muqueuse gastrique: étude histologique, bactériologique et résultats préliminaires d'une enquête épidémiologique dans la région nantaise.

The aims of this study were to: a) evaluate the prevalence of Campylobacter pylori (CP) in patients referred to a gastroenterology unit for upper digestive tract endoscopy, b) compare the results of histologic (Warthin-Starry method) and bacteriologic (direct and culture) examinations, c) correlate the presence and abundance of CP with the "activity" of chronic gastritis as assessed by antral and fundic specimens, and d) report the preliminary results of an epidemiological survey in the area of Nantes, France. CP was observed in 30 of the 64 patients studied (46 p. 100 of cases), and was significantly associated with chronic gastritis of either the superficial or interstitial (87 vs. 12 p. 100 of patients positive and negative, respectively for CP studies, p less than 10(-9], and preatrophic and/or atrophic types (40 vs. 12 p. 100 of patients positive and negative, respectively, for CP studies, p less than 0.01). CP was also present in 7 of 10 patients with duodenal ulcers and in 4 to 6 with gastric ulcers. Histologic and bacteriologic studies gave concordant results in 94 p. 100 of cases, and had the same sensitivity for diagnosis. Patients positive for CP studies had a statistically significant increased incidence of epigastric burns, and, at endoscopic examination, their fundic area appeared congestive more frequently. CP were dictated in both the antrum and fundus, but lesions of chronic gastritis were more prominent in the former. There was a statistically significant correlation between the degree of inflammation observed in the lamina propria and the number of CP present in the same area (antrum and fundus).(ABSTRACT TRUNCATED AT 250 WORDS)

Low dose omeprazole effects on gastric acid secretion in normal man.

The pharmacological effects of low dose of omeprazole (Om) are not well known. This prompted us to investigate the effects of a 7-day treatment with a low dose of Om, 10 mg/d (Om10), on gastric acid secretion and serum gastrin levels and to compare the results with those obtained with an effective antisecretory dose of 20 mg/d (Om20). Twelve healthy volunteers received randomly and double-blind for three periods of 7 days, separated by at least 7 days, one capsule of placebo (P), Om10, Om20, given daily in the morning, in fasting condition. The last day of each period, 24 h pH was recorded using a glass electrode connected to a Digitrapper (Synectics). At the end of each pH-metry, acid secretion was measured in basal conditions (BAO), after sham-feeding (SAO) and after i.m. injection of 6 micrograms X kg-1 of pentagastrin (PAO). Whatever the threshold pH chosen, there was a statistically significant difference between P and Om10, P and Om20, and Om10 and Om20. Inhibition of acid concentrations was dose-dependent and prolonged, including nocturnal time. However, when considered on an individual basis, five subjects did not respond to Om10. More than 24 h after the last dose of Om has been administered, BAO, SAO and PAO were significantly reduced by either Om10 (respectively -52, -35 and -28 p. cent) and Om20 (respectively -60, -58 and -50 p. cent). Fasting serum gastrin concentration was significantly increased after Om20 treatment but not after Om10. We conclude that treatment with Om10 has a consistent and long lasting inhibitory action on gastric acidity without statistically significant effect on serum gastrin levels. These results suggest that 10 mg Om daily should be sufficient in some duodenal ulcer patients to effectively inhibit gastric acidity specially when long-term treatment seems to be indicated.

[Ogilvie's syndrome: results of endoscopic exsufflation in a series of 29 cases]. / Syndrome d'Ogilvie: résultats de l'exsufflation endoscopique dans une série de 29 cas.

The aim of this study was to assess the value of endoscopic decompression of the colon in a series of 29 patients affected with Ogilvie's syndrome. During the first period (1980-1982), 14 patients were treated by colonoscopic decompression alone. During the second period (1982-1985), 15 endoscopic decompressions were systematically completed by intubation of the colon. The tube was removed after 2 to 13 days. Whatever the procedure, endoscopic decompression was successfully achieved in all cases. The death rate (8/29) and number of cecostomies (2/29) were similar in the two groups of patients. Only one death was directly related to Ogilvie's syndrome itself, whereas 7 patients died from other severe underlying diseases. However, colonic dilatation recurred in 6 patients in the first group and in one patient in the second group (p less than 0.05). No complications due to the endoscopic procedures occurred in this series. It may be concluded that endoscopic treatment of Ogilvie's syndrome is a safe and effective procedure. Our results also suggest that colonoscopic intubation should be used prophylactically in order to avoid recurrences, frequently observed after simple endoscopic decompression.

[Pseudo-angina pain of esophageal origin. Results of functional study and value of the balloon distention test]. / Douleurs pseudo-angineuses d'origine oesophagienne. Résultats de l'exploration fonctionnelle et intérêt du test de distension mécanique par ballonnet.

In patients with angina-like chest pain, the diagnostic value of esophageal investigations has not been definitively established. The aim of this study was to assess the diagnostic value of different esophageal investigations in 45 patients (group I) with angina-like chest pain for which a cardiac origin had been previously excluded. These investigations included esophageal manometry, Bernstein test, edrophonium test, balloon distention test, and 24-hour pH monitoring (with event marker). These patients were compared to two control groups: a) 9 subjects with documented coronary disease (group IIa), and b) 9 healthy volunteers (group IIb). Abnormal results were observed in 37 patients in group I (82 percent), and in 4 patients in group IIa (44 percent). In group I, manometry was abnormal in 29 percent of patients and pH monitoring in 41 percent; provocative tests were positive in 10 percent, 15 percent, and 38 percent for the Bernstein test, edrophonium test, and balloon distention test respectively. Esophageal origin of the pain was shown to be likely in 36 percent of patients in group I. These results confirm the high incidence of functional abnormalities of esophagus in patients with angina-like chest pain. They also confirm the diagnostic value of the different provocative tests and especially the balloon distention test.

[Primary sclerosing cholangitis and systemic lupus erythematosus]. / Cholangite sclérosante primitive et lupus érythémateux systémique.

We report the association of primary sclerosing cholangitis and systemic lupus erythematosus in a 39 year-old man. Six months after a diagnosis of primary sclerosing cholangitis was established, the patient was hospitalized for a pleural effusion and acute pericarditis. Emergency pericardiocentesis, was required due to sudden cardiac tamponnade. Plasmatic anti-DNA and anti-nuclear antibodies were present. Treatment by steroids greatly improved symptoms. This clinical association suggests that some immune disorders may be common to the two diseases.

[Natural history of non alcoholic and non familial chronic pancreatitis. Results of a multicentre study]. / Evolution de la pancréatite chronique non alcoolique et non familiale.Résultats d'une étude multicentrique.

UNLABELLED: The natural history and complications of non alcoholic chronic pancreatitis (NACP) is poorly understood compared to that of alcoholic chronic pancreatitis (ACP). PATIENTS AND METHODS: From April 1993 to April 1996, 77 patients with NACP were prospectively evaluated in 17 French centres. This population was compared to a cohort of 417 patients with ACP. RESULTS: No significant difference was observed with respect to mean age between NACP and ACP (43 +/- 20 vs 44 +/- 11 years, respectively). The median patient follow-up time was also comparable: 7 years (1-28) and 6 years (1-34) respectively for NACP and ACP. There were significantly more males in the ACP group (9/1 in ACP group and 1.3/1 in NACP group; P<10(- 7) ). Patients with NACP were less likely to have calcifications (58% vs 77%; P=0.01), pseudocysts (19 vs 47%, P<0.001), portal vein thrombosis (5 vs 16%, P<0.02). Importantly, patients with NACP required less surgical procedures than those with ACP (26% vs 44%, P=0.004). The actuarial death rate at 15 years was 0% in the NACP group compared to 20.5% in those with ACP (no CP related death). CONCLUSION: NACP has a less severe disease progression, fewer complications and requires less surgical interventions than ACP. The lower actuarial survival rate in patients with ACP correlates with the extra-pancreatic complications encountered in patients with alcohol related diseases and not with the evolution of CP itself.

Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

[Importance of using hematoporphyrine derivate in the destruction of adenocarcinomas with Nd Yag or argon lasers]. / Intérêt de l'utilisation de l'hématoporphyrine dérivée pour la destruction d'adénocarcinomes par le laser N.D. Yag ou le laser á argon.

As the hematoporphyrin derivate photochemical properties have been known for many years, this study tries to appreciate the laser beam effect on experimental tumors previously sensitized by H.P.D. Colic adenocarcinoma cells are grafted on mice. On the 10th day tumors are photocoagulated. Previously the mice were divided into 4 groups: G 1: H.P.D. intra-venous injection on the 9th day followed by a Nd Yag laser photocoagulation; G 2: Nd Yag laser only; G 3: H.P.D. intra-venous injection on the 9th day followed by an argon laser photocoagulation; G 4: argon laser only. The G 1 and G 2 study shows that, when Nd Yag laser is used, H.P.D. alters the type of necrosis obtained and the action depth. The G3 and G4 study shows that, when argon laser is used, H.P.D. does not alter the type of necrosis obtained but greatly increases the action depth.

[Multiple granular cell tumor of the colon]. / Tumeur à cellules granuleuses colique plurifocale.

With reference to a case of multiple colorectal granular cell tumors, the authors briefly review the literature concerning this unusual tumor localization. This case demonstrates the most common appendicular, caecal and rectal forms among the localizations of colonic granular cell tumors: as well as the possible proliferation of many other tumors especially in caecal localizations. However the course of the disease is slow, and at the present time only one case report of malignant colonic TCG has been published.

[Palliative treatment by photochemotherapy of 54 digestive cancers: phase I clinical trial]. / Traitement palliatif par photochimiothérapie de 54 cancers digestifs: essai clinique de phase I.

Photochemotherapy (PDT) is based on the interaction of a phototoxic drug (HPD) retained by cancer tissues and excited with a specific laser light. We present here a phase I clinical trial including 54 patients selected on the grounds of non-operability and T1 NO MO staging (UICC) and divided into 3 groups: I) 24 squamous cell carcinoma (SCC), II) 14 adenocarcinomas (ADN) of the upper GI tract, III) 16 ADN of the rectosigmoid colon. All received an HPD infusion of 2.5 to 5 mg/kg I.V. 72 hours before being laser irradiated endoscopically (632 nm, 150 to 220 j/cm2). Results documented on histology obtained after grip biopsies and on resected specimens (6 cases), were classified as complete response (ST), partial response (PR) or no change (NC). Eleven patients of group I, 5 of group II, and 8 of group III (24/54 patients) were classified ST with a mean follow-up of 15.2 months. Analysis of resected specimens showed a complete disappearance of tumor tissue and prominent fibrosis all around the treated area. Adverse effects were noted in 22% of patients, PDT of rectosigmoid ADN gave a survival (life table analysis) at least equal to SCC. These results should allow clinical indications for PDT to be broadened in combined protocols.

[Peritoneal amyloidosis in Waldenström's macroglobulinemia. X-ray computed tomographic aspects]. / Amylose péritonéale au cours d'une macroglobulinémie de Waldenström. Aspect tomodensitométrique.

A 74 years old man, know to have Waldenström's macroglobulinemia was hospitalized for intestinal obstruction. Upper gastrointestinal barium study revealed an extrinsic stenosis of duodenum. Ultrasonography and abdominal computed tomography revealed a diffuse mesenteric infiltration with medium level echoes and encasing of mesenteric vessels. Histologic examination of biopsies taken at exploratory laparotomy disclosed amyloidosis of the epiploon and mesentery. The review of amyloidosis in macroglobulinemia shows peritoneal amyloidosis to be a very rare event. Sonographic, computed tomographic and pathologic findings of this unusual case are discussed.

[The stimulation of tumoricidal peritoneal macrophages can be directly induced by peritoneal implantation of unicellar algae in humans]. / La stimulation des macrophages péritoneaux tumoricides peut être directement provoquée par l'implantation péritonéale d'algues unicellulaires chez l'humain.

The authors explain by what means they have been conducted to use the anti-tumoral power shown by the peptido-glycans produced in the wall of unicellular algae. The first human trials when the algae are introduced in the peritoneal cavity have shown a good tolerance.