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A Roche

Publications and source records attributed to A Roche.

At least 19 recordsLinked to original sources
PubMed1997

Somatostatin and growth hormone-releasing hormone in normal and tumoral human breast tissue: endogenous content, in vitro pulsatile release, and regulation.

Endogenous production of SRIH and GHRH was analyzed in human breast tissue. SRIH precursor (pro-SRIH) was identified after Sephadex G-50 filtration of acetic acid extracts of normal and tumoral human breast samples. SRIH-(1-14) or -(1-28) could not be detected in breast tissue, whereas the immunoreactive SRIH released in vitro was characterized as SRIH-(1-28). Endogenous production of GHRH was assessed by identification of GHRH messenger ribonucleic acid by PCR followed by sequencing of the amplified complementary DNA and by high performance liquid chromatographic characterization of immunoreactive GHRH contained in the tissue and released in vitro. There were no differences in pro-SRIH or GHRH-(1-44) tissue contents between normal and tumoral samples. The release of both peptides was evidenced in perifusion and static incubation. Perifusion of normal breast tissue (n = 3) showed pulsatile release of SRIH and GHRH. Perifusion of tumors (n = 4) showed SRIH release in 50% of the cases. SRIH release was pulsatile in one case. GHRH release was observed in the four tumoral samples analyzed, but was pulsatile in only one case. In static incubation, tumors (n = 6) secreted 13 times more GHRH than did normal samples (n = 3; 383 +/- 92 vs. 29.6 +/- 4.6 fmol/mg protein; P < 0.05). Stimulation of GHRH release by exogenous SRIH was observed only with the normal tissue. Together these data provide evidence for the existence of local production of SRIH and GHRH by human breast. Hypersecretion of GHRH by breast tumors indicates that this peptide could play a role in maintaining epithelial cell proliferation as is the case for other peptides produced locally.

Breast↗
PubMed1996

Liver abscess formation after local treatment of liver tumors.

Our goal was to determine a subset of patients at high risk of developing liver abscesses after local treatment of liver tumors (LTLT) and establish guidelines for the conduct of LTLT in the safest conditions in such patients. Five hundred sixty-one LTLT, 489 transhepatic arterial chemoembolizations (TAC, 10 hepatic embolizations, and 62 percutaneous intratumor injections (PIT), were retrospectively reviewed for liver parenchyma necrosis and abscess formation. Four patients developed abscesses, three after TAC and one after PIT. Despite broad-spectrum antibiotherapy, percutaneous drainage, and surgery, two patients died. A left hepatectomy was required in the other two patients for cure. All four patients had a carcinoid or a neuroendocrine pancreatic tumor. Three out of four patients had bilioenteric anastomoses, and the fourth had recently undergone cholecystectomy and papillotomy. A Lipiodol/doxorubicin mixture without any particulate embolization was injected in the three patients who developed abscesses after TAC. LTLT in patients with bilio enteric anastomosis or papillotomy and/or neuroendocrine or carcinoid tumor should be performed with strict precautions during the procedure and for peri-procedural care.

Antineoplastic Agents↗
PubMed1996

Decrease of ciliary beat frequency by platelet activating factor: protective effect of ketotifen.

The ciliary beat frequency (CBF) of the tracheal epithelial cells controls in part the respiratory tract mucociliary transport efficiency. We investigated the effects on CBF of PAF-acether (PAF) and its metabolite/precursor lyso-PAF. Guinea-pig tracheal rings were incubated for 3 to 6h with 1 microM PAF (C16, C18, C16/C18: 80/20%), lyso-PAF C16 or lyso-phosphatidylcholine (LPC). CBF changes were assessed by microphotooscillography (mean number of measures per ring = 14). We also examined the effect on PAF-induced CBF changes of the PAF receptor-antagonist WEB 2086, the anti-asthmatic/anti-anaphylactic drug ketotifen and the anti-histamine H1 pyribenzamine. CBF of control rings exposed to vehicle only from 0 to 6h showed no significant statistical variations (hertz, mean +/- SEM): 10.8 +/- 0.1 (n of measures = 890). By contrast, 1 microM C16, C18, and C16/C18 PAF significantly inhibited CBF after 3 to 6h incubation. C16 and C16/C18 PAF were more potent than C18 PAF (8.8 +/- 0.2, n = 112, 8.7 +/- 0.2, n = 64, and 9.6 +/- 0.1, n = 537 respectively; ANOVA analysis, p < 0.001 from control). At the same concentration, lyso-PAF also inhibited CBF, 9.5 +/- 0.1 (n = 197, p < 0.001) but not LPC, 10.5 +/- 0.2 (n = 127). WEB 2086 inhibited lyso-PAF and C16/18 PAF-induced CBF decrease. Preincubation (20 min) with ketotifen but not with pyribenzamine (1 microM) also suppressed the CBF inhibitory effect of PAF and lyso-PAF. Incubation of [3H]PAF with tracheal rings from 10 min to 6h resulted in its partial metabolism (25%) into [3H]lyso-PAF and a compound with a short retention time (10 min). [3H]lyso-PAF incubated for 3h with tracheal rings was partially metabolized (10%) into [3H]PAF and a compound with a short retention time. The PAF-induced decrease of CBF is congruent with its influence on pulmonary clearance, possibly via a specific receptor, since WEB 2086 abolished the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen may contribute to the therapeutic properties of this antiallergic drug.

Animals↗
PubMed1996

Preoperative portal vein embolization for extension of hepatectomy indications.

To render hepatectomy feasible in patients with an initially deficient volume of the future remnant liver (FRL), we redistributed portal blood flow rich in hepatotrophic substances toward the FRL. Redistribution was achieved with preoperative portal vein embolization (POPE) feeding the future resected liver. POPE was performed in 31 patients, under fluoroscopic guidance, via a percutaneous access. POPE was well tolerated and surgery was practicable in 24 patients without severe postoperative liver failure. Seven operations were cancelled, but only one due to insufficient hypertrophy of the FRL. FRL volume values were 90 to 560 mL (mean 260 mL) before POPE and 160-783 mL (mean 443 mL) after POPE, which represents a median increase of 79% +/- 50%. Hypertrophy of the FRL was 90% +/- 52% after 30 days with cyanoacrylate, 53% +/- 6% after 43 days with Gelfoam, and 44% +/- 30% after 35 days with coils. Slight shrinkage was obtained in the volume of the embolized liver, for which resection was planned. Overall survival was 2-62 months (mean 26 months), disease-free survival was 0-60 months (mean 19 months), and 7 patients are disease-free and alive 14 to 60 months (mean 43 months) after surgery. Although exclusively applicable in a limited subset of patients, POPE widens the possibilities of curative hepatectomies, because it induces sound hypertrophy of unembolized liver segments. Cyanoacrylate seems to ensure better and faster hypertrophy.

Adolescent↗
PubMed1996

Quantification of tumor uptake of iodized oils and emulsions of iodized oils: experimental study.

PURPOSE: To optimize use of iodized oil for diagnostic computed tomography (CT) enhanced with iodized oil and for interstitial radiation therapy with iodine-131-labeled iodized oil, the authors quantified the distribution of iodized oil after injection of different formulations of iodized oil into the hepatic artery. MATERIALS AND METHODS: I-125-labeled iodinated ethyl ester of poppyseed oil in two viscosities (iodized oil ultrafluid [viscosity, 0.04 Pa/sec] and iodized oil fluid [viscosity, 0.17 Pa/sec]) was injected (pure forms and three different emulsions of each) into the hepatic artery of rabbits bearing VX2 tumors in the liver. All rabbits received a radiation dose of 4 MBq per kilogram of body weight in 0.1 mL/kg iodized oil. Animals were killed 4 days later, and iodized oil uptake was evaluated in the tumor, nontumorous liver, and lung. RESULTS: There were no statistically significant differences in uptake between pure iodized oil ultrafluid or fluid or between the same type of emulsions made with each type of iodized oil. Lung uptake was significantly higher with pure iodized oil ultrafluid and fluid (19.75 kBq/g +/- 3.25 [standard error of the mean] vs 19.48 kBq/g +/- 6.15, respectively) than with any emulsions (range, 3.72-8.14 kBq/g; mean, 5.68 kBq/g) except the small-droplet oil-in-water emulsion (10.51 kBq/g +/- 1.18). The ratio of tumor to nontumorous liver uptake of iodized oil was significantly higher with large-droplet water-in-oil emulsions made of iodized oil ultrafluid or fluid (10.26 +/- 2.88 and 9.53 +/- 0.64, respectively) than with any other product (range, 4.07-5.38; mean, 4.49). CONCLUSION: Use of large-droplet water-in-oil emulsions limited lung uptake and increased tumor uptake of iodized oil after intraarterial hepatic injection in rabbits bearing VX2 tumors in the liver.

Animals↗
PubMed1996

Comparison of octreotide scintigraphy and conventional imaging in medullary thyroid carcinoma.

UNLABELLED: We evaluated the clinical utility of positive somatostatin receptor scintigraphy in patients with medullary thyroid cancer (MTC). METHODS: Twenty-four MTC patients with increased calcitonin levels underwent somatostatin receptor scintigraphy using 111In-pentetreotide (120-200 MBq) with early (4 hr after injection) and delayed (24 hr) whole-body scans and liver SPECT imaging. In Group 1 (12 patients), conventional imaging modalities demonstrated the presence of tumor sites prior to somatostatin receptor scintigraphy; in Group 2 (12 patients), conventional imaging modalities were negative or inconclusive. RESULTS: Somatostatin receptor scintigraphy had positive results in 9 of 24 patients (37%): of Group 1 patients, 7 of 12 had positive somatostatin receptor scintigraphy results. Of these patients cases, somatostatin receptor scintigraphy demonstrated several involved organs and tumor sites either identical (two patients) or smaller (five patients) in size than conventional imaging modalities. Only two patients in Group 2 had positive somatostatin receptor scintigraphy results which demonstrated significant mediastinal uptake previously classified as indeterminate on conventional imaging modalities. No new tumor site was identified nor were therapeutic options modified by the somatostatin receptor scintigraphy results. CONCLUSION: Somatostatin receptor scintigraphy only demonstrates part of tumor sites and cannot visualize small tumor sites (< or = 1 cm). We believe that somatostatin receptor scintigraphy has a limited role in the management of MTC patients.

Adult↗
PubMed1996

[Major hepatectomy after intra-arterial chemotherapy for initially unresectable liver tumors. Frequency, technical problems, results and indications].

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resecable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This draw-back is circumvented by using techniques: such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major, hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗
PubMed1995

[Treatment of metastatic malignant insulinomas. 2 cases].

Malignant insulinomas are slow growing tumours for which the prognosis is worsened by metastatic disease and sequellae of excess hormone secretion. Management of unresectable tumours includes intravenous chemotherapy and local treatments such as palliative surgery and transcatheter arterial embolization of liver metastases. Long-term survival can also be improved by inhibition of secretory products of the tumour with either octreotide, a somatostatin analogue, or diazoxide. We report two cases of malignant insulinomas with liver metastases for which objective responses were obtained with combination of local treatment and intravenous chemotherapy.

Aged↗
PubMed1995

[Transient arrhythmia disclosing major glycine poisoning during hysteroscopy].

We report the case of a 41-year-old ASA I patient who experienced during endometrial resection a transient idioventricular cardiac rhythm with hypotension related to a major glycine intoxication. The total volume of absorbed irrigating fluid was over six liters when these clinical signs occurred. The biological data were as following: Na = 89 mmol.L-1, Cl = 60 mmol.L-1 and osmolarity = 215 mOsm.L-1. Simultaneously, the glycine concentration in the plasma was 54.6 mmol.L-1, i.e 160 times higher than the normal value. The clinical course was unremarkable except vomiting. The treatment included only the administration of a diuretic agent, as the correction of the disorder took place spontaneously. The paucity of clinical symptoms when compared to the severity of the biological disorders explain why preventive measures are essential in this type of surgery.

Accelerated Idioventricular Rhythm↗
PubMed1995

Circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil and doxorubicin: experimental study.

PURPOSE: To evaluate circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil with an anticancer drug. MATERIALS AND METHODS: The viscosities and stability were evaluated in arterial flow of iodized oil and the emulsions. Doppler ultrasound was used to quantify the embolic effect in the arteries of rabbits. The behavior of doxorubicin and iodized oil in the rat cremaster muscle was studied with videomicroscopy. RESULTS: The emulsions did not break up after injection, and the size of discontinuous-phase droplets did not change. The embolic effect did not correlate with viscosity. The thinnest water-in-oil emulsion had the lowest embolic effect and induced homogeneous distribution of iodized oil droplets in the arterial tree. CONCLUSION: Changes in the formulation of emulsions obtained with the same proportions of drug and iodized oil change the distribution of iodized oil in the arterial tree, the location at which the drug is released, and the embolic effect.

Abdominal Muscles↗
PubMed1995

Frequency, technical aspects, results, and indications of major hepatectomy after prolonged intra-arterial hepatic chemotherapy for initially unresectable hepatic tumors.

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility, and results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5) or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resectable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44, and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This drawback is circumvented by using techniques, such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗
PubMed1994

Selective venous sampling catheterisation for localisation of persisting medullary thyroid carcinoma.

Selective venous sampling catheterisation was performed in 19 patients with medullary thyroid carcinoma without known distant metastases for persistent hypercalcitoninaemia after surgery. Calcitonin (CT) gradients were found in the neck and/or the mediastinum in 18 patients and in five patients at distant sites also. After venous catheterisation, 13 patients were subjected to repeat surgery. Neck and/or mediastinal tumour foci were found in 12 patients at the sites of the CT gradients. Of these, nine patients had only cervicomediastinal CT gradients: after reoperation, the serum CT level normalised in one, significantly decreased in five, and did not change in three, and no neck relapse occurred after a mean follow-up of 5.3 years. Distant metastases emerged clinically in all five patients with distant gradients and in only one of the 14 patients with no distant gradient. In conclusion, selective venous catheterisation is the most sensitive tool for the localisation of residual disease and for the early detection of distant metastases. However, in patients with only local disease, biochemical cure is rarely obtained after reoperation.

Adolescent↗
PubMed1994

Management of clinically relevant bleeding following endoscopic sphincterotomy.

We report here on our experience of clinically relevant bleeding after endoscopic sphincterotomy (ES). Relevant bleeding was defined by the occurrence of (a) hematemesis or melena and (b) at least a two-point drop in hemoglobin, with no other bleeding source on endoscopy. These two criteria were met in 16 patients between 1983 and 1992. They represented 0.65% of all ES procedures performed during this period. Bleeding occurred immediately after ES in five cases, and was delayed in 11 cases from one to eight days (mean two days). Patients were retrospectively classified into three groups according to the severity of bleeding and subsequent clinical management. In six cases (group 1), bleeding developed slowly without shock and stopped spontaneously. In five cases (group 2), bleeding developed rapidly with melena and a drop in hemoglobin, but without shock. These patients were successfully managed with sclerotherapy without any further complications. The five patients in Group 3 had brisk bleeding with hematemesis and shock. Endoscopic hemostasis could not be performed; emergency arteriography disclosed active bleeding in four patients, and embolization of the gastroduodenal artery was performed. Bleeding stopped in all patients. Billroth II anastomosis appeared to be the only factor associated with an increased risk of clinically relevant bleeding. It was possible to control bleeding following ES using endoscopic or angiographic hemostasis, surgery being avoided in all cases.

Adult↗
PubMed1994

Ureteral stents: exchange under fluoroscopic control as an effective alternative to cystoscopy.

From September 1991 to February 1993, in 83 patients (74 women and nine men, aged 24-86 years), 166 double-J ureteral stents (initially placed to treat fistulas or stenoses located within the inferior third of the ureter) were exchanged during 127 procedures. Stents were extracted from the bladder through the urethra under fluoroscopic monitoring by using a lasso made of a 0.018-inch guide wire and a 7-F catheter. Then a new stent was placed over a 0.035-inch guide wire that had been previously coiled in the renal pelvis. Exchange was successful in 161 (97%) of 165 stents.

Adult↗
PubMed1994

[Contribution of the artificial pancreas in the diagnosis and surgical treatment of insulinomas].

Insulinomas are often hard to diagnose and difficult to locate during surgery. We tested the contribution of artificial pancreas (AP) for case management of our last eight patients including two cases with multiple insulinomas. When diagnosis is uncertain, the euglycemic hyperinsulinic clamp technique under AP is a safe method to assess inappropriate insulin secretion characterized by a high plasma level of C peptide not inhibited by insulin injection. During surgery the AP provides a feed back controlled glucose infusion and thus maintains blood glucose above a predefined level. It allows a safe operation, preventing sudden hypoglycemia. By providing continuous data about intensity of glucose infusion and blood glucose, it helps to detect an occult secreting tumor (a preoperative therapeutic test with diazoxide requires stopping treatment for at least one month before surgery to avoid false negative results) and confirms the total ablation of abnormal insulin-producing cells. Peroperative monitoring curves of glucose infusion and blood glucose related to exploration and ablation procedures illustrate the contribution of this method in helping surgical treatment which can be perfectly adapted to the lesions as shown by the total recovery of our eight patients (mean follow-up: 43.2 months).

Artificial Organs↗
PubMed1993

Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients.

BACKGROUND: Liver metastases of endocrine tumors are of major prognostic significance. The various therapeutic approaches have given disappointing results; however, locoregional treatment has allowed transient control of hepatic tumor growth. METHODS: Twenty-four patients with liver metastases of endocrine tumors (mainly carcinoid tumors [n = 18] and gastrinomas [n = 5]) were included in a Phase II study of hepatic arterial chemoembolization (CE). Metastases were bilateral in all patients and invaded more than 50% of the liver in 12. They were synchronous of the primary tumor in 62.5% of the patients. Seventeen patients had not responded to previous intravenous chemotherapy. CE courses were performed every 3 months using an emulsion of 10 ml of iodized oil and doxorubicin 50 mg/m2 injected into tumor vessels, followed by CE arterial occlusion with gelatin sponge particles. Seventy-one CE courses were performed in 23 patients; there was one technical failure. RESULTS: Among patients with carcinoid tumors, disappearance of diarrhea and/or flushing was observed in 8 of 11. Serotonin and/or its metabolite 5-hydroxyindoleacetic acid levels decreased by more than 50% in 57% of the patients. The size of liver metastases decreased by at least 50% in 6 of 18 patients, i.e., in 33% (range, 12-54%). Two had complete responses. The median duration of the responses was 14 months (range, 6-40). Among patients with noncarcinoid tumors, minor response or stabilization occurred in three of five patients. Major side effects were bleeding peptic ulcer (one patient) and oligoanuric renal failure (one patient). Abdominal pain, fever, and increases in hepatic enzyme levels were common and transient. CONCLUSIONS: These results suggest that CE is effective in patients with liver metastases of endocrine tumors, mainly in carcinoids. In the latter, CE allows control of the carcinoid syndrome and regression or stabilization of the liver tumors in 80% of patients.

Adult↗