Carcinogenic potency of perfluorooctane sulfonate (PFOS) on Syrian hamster embryo (SHE) cells.

Perfluorooctane sulfonate (PFOS) is the degradation product of many fluoroderivatives and a widespread environmental contaminant. Its persistence, its long half-life in humans and its toxicity explain high concerns on human health side effects in future. PFOS is suspected to be a non-genotoxic carcinogen. In the present work, we assessed carcinogenic potential of PFOS by studying morphological transformation in Syrian hamster embryo (SHE) cells; cell transformation of SHE cells is an in vitro assay recommended by the Organization for Economic Cooperation and Development to detect carcinogens, genotoxic or not. Genotoxicity of PFOS and expression of PPARs genes in SHE cells were also measured. PFOS was shown to induce cell transformation (P < 0.05) at non-cytotoxic concentrations (0.2 and 2 µg/mL) (P ≤ 0.01). No genotoxic effect was recorded in the range of PFOS concentrations tested (2 × 10(-4) to 50 µg/mL) using the single-cell gel electrophoresis (comet) assay after 5 and 24 h of exposure. The expression of PPARs genes was measured by qPCR within the first 24 h and after 7 days of PFOS treatment. Results indicated an increased expression of ppar-ß/δ isoform as early as 24 h. After 7 days, the increase of ppar-ß/δ mRNA was significant at the concentrations inducing cell transformation (0.2 and 2 µg/mL), while overexpression of ppar-γ and ppar-α did not closely relate to effective concentrations. The results indicate that PFOS behave as a non-genotoxic carcinogen and impacted PPARs genes. Its cell transforming potential paralleled an increased expression of ppar-ß/δ.

Follow-up of stable chromosomal aberrations in gamma-ray irradiated non-human primates.

PURPOSE: The purpose of this study was to examine a new approach to retrospective biological dosimetry, by using a long-term animal model to determine the stability of translocation frequency after in vivo irradiation. While the frequency of dicentrics is known to decrease over time, the persistence of more stable chromosomal aberrations such as translocations could be useful if their stability were definitively proved. MATERIALS AND METHODS: Four monkeys (Macaca fascicularis) were exposed to two different doses of ionizing radiation: 2 Gy whole body irradiation for two and 4 Gy for two others. Blood samples were obtained at various times after irradiation. Both total and two-way translocations were detected by fluorescence in situ hybridization. Translocations were scored in stable cells, that is, those without dicentrics, rings or fragments. The course of translocation frequency was analysed at four time-points: one hour (H1), 2 months (M2), 10 months (M10) and 31 months (M31) after irradiation. RESULTS: We observed two separate trends in translocation frequency: Total translocation frequency decreased slightly in animals irradiated with a dose of 2 Gy, while two-way translocation frequency was relatively stable in all irradiated animals. CONCLUSIONS: We confirmed the long-term stability of translocations and found that it seems to depend on the type of the translocation recorded. Overall translocations were stable for up to 31 months regardless of dose, but two-way translocations were more stable than those that were non-reciprocal, especially in stable cells.

Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine.

OBJECTIVES: We investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes induced by PNO by reducing release of catecholamines and vasopressin. BACKGROUND: Both mechanical and neurohumoral factors contribute to the hemodynamic changes induced by carbon dioxide PNO. Several mediators have been proposed, but no study has correlated hemodynamic changes with changes in levels of these potential mediators. METHODS: We conducted two studies, each including 20 healthy patients scheduled for elective laparoscopic cholecystectomy. In the first study serial measurements of hemodynamics (thermodilution technique) were done during laparoscopy and after exsufflation. Plasma concentrations of cortisol, catecholamines, vasopressin, renin, endothelin and prostaglandins were measured at the same time points. In the second study patients were randomly allocated to receive 8 microg/kg clonidine infused over 1 h or placebo before PNO. Hemodynamics and plasma levels of cortisol, catecholamines and vasopressin were measured during PNO and after exsufflation. RESULTS: Peritoneal insufflation resulted in a significant reduction of cardiac output (18+/-4%) and increases in mean arterial pressure (39+/-8%) and systemic (70+/-12%) and pulmonary (98+/-18%) vascular resistances. Laparoscopy resulted in progressive and significant increases in plasma concentrations of cortisol, epinephrine, norepinephrine and renin. Vasopressin plasma concentrations markedly increased immediately after the beginning of PNO (before PNO 6+/-4 pg/ml; during PNO 129+/-42 pg/ml; p < 0.05). The profile of vasopressin release paralleled the time course of changes in systemic vascular resistance. Prostaglandins and endothelin did not change significantly. Clonidine significantly reduced mean arterial pressure, heart rate and the increase in systemic vascular resistance. Clonidine also significantly reduced catecholamine concentrations but did not alter vasopressin and cortisol plasma concentrations. CONCLUSIONS: Vasopressin and catecholamines probably mediate the increase in systemic vascular resistance observed during PNO. Clonidine before PNO reduces catecholamine release and attenuates hemodynamic changes during laparoscopy.

Organ donors with primary central nervous system tumor.

Patients with primary central nervous system (CNS) tumor have been accepted for organ donation because these tumors very rarely spread outside the CNS. However several case reports of CNS tumor transferral with organ transplantation recently challenged this attitude. Some risk factors for extraneural spread of CNS tumors have been determined, but the absence of risk factors does not exclude the possibility of metastases. To our knowledge, 13 cases of CNS tumor transferral with organ transplantation (one heart, three livers, eight kidneys, one kidney/pancreas) have been reported in the literature. Even if no prospective evaluation of the CNS tumor transmission risk with transplantation has been undergone, this risk may be estimated between a little more than 0% and 3% from retrospective series. The authors consider that patients with CNS tumor should be accepted as donors as long as the risk of dying on the waiting lists is significantly higher than the tumor transferral risk. Therefore the authors would have no restriction for transplanting organs from donors with benign or low-grade CNS tumor. For high-grade tumors, the authors would consider these donors as "marginal donors," and balance the risk of tumor transmission with the medical condition of the recipient.

Cytokines and organ transplantation. A review.

Cytokines regulate both aspecific inflammatory responses and specific immune responses. Inflammatory changes occur in the organ transplant as a result of tissue trauma and ischemia/reperfusion in the organ donor and at the time of transplant operation. There is a possibility that cytokines play a role in mediating theses changes. These aspecific inflammatory changes may not only affect graft function but also influence graft immunogenicity (enhanced MHC and adhesion molecule expression) and thus, vulnerability to rejection. Cytokines orchestrate the specific immune response elicited by organ transplantation. Relevance of cytokines to the rejection reaction is multifactorial in nature: 1) promotion of the proliferation an differentiation of specific alloreactive T and B cells clones and differentiation and activation of CTL and NK cells, 2) chemotactic effect and induction of the expression of adhesion molecules, 3) enhancement of MHC class I and II expression, and 4) direct cytotoxic effect on the target grafted cells. Therefore, modulation of cytokine activity either specifically (monoclonal antibody, soluble receptor, etc.) or aspecifically (cyclosporin, FK 506, Rapamycin, steroids, etc.) is essential in controlling graft rejection. Determination of circulating cytokines and cytokines measurement within the biological fluids produced by an organ transplant may help in the diagnosis of rejection episodes and other complications following organ transplantation.

Abdominal wall metastasis and peritoneal carcinomatosis after laparoscopic-assisted colectomy for colon cancer.

We report a case of a port-site recurrence with diffuse peritoneal carcinomatosis after laparoscopic-assisted right hemicolectomy. The interval between resection of the colonic adenocarcinoma and diagnosis of the recurrence was short (1 month), suggesting that intraperitoneal dissemination and tumour implantation on surgical wounds may represent the principal mechanism of recurrence after laparoscopic surgery. Review of the literature shows an alarming increase in the occurrence of this devastating complication. Although beneficial to the patient in the immediate post-operative period, the adequacy of laparoscopic-assisted colectomy in tumour is increasingly under question.

Level of Flt3-ligand in plasma: a possible new bio-indicator for radiation-induced aplasia.

PURPOSE: To follow plasma Flt3-ligand (FL) concentrations in irradiated animals in order to evaluate it as an indicator of bone marrow damage for the management of accidental radiation-induced aplasia. MATERIALS AND METHODS: Non-human primates were irradiated at doses ranging from 2 to 8 Gy, using whole- or partial-body irradiation. Plasma FL concentrations and blood cell counts were determined daily. RESULTS: FL concentrations increased as early as day 2 after irradiation, whatever the irradiation dose. Increase in plasma FL concentration on day 5 post-irradiation was correlated with radiation dose and with the severity of radiation-induced aplasia. During the course of aplasia, FL concentrations in plasma were inversely correlated with neutrophil counts. A peak in FL concentration appeared before the neutrophil nadir, and the subsequent decrease in FL concentration was correlated with the recovery of blood-cell populations. CONCLUSIONS: Monitoring plasma FL concentration can be used as an indicator of radiation-induced marrow aplasia, and this may be of use in accidental irradiation situations.

Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.

Early stage results after oesophageal resection for malignancy - colon interposition vs. gastric pull-up.

OBJECTIVE: The aims of our study were to determine if using the colon as a digestive transplant after oesophagectomy for cancer was associated with increased postoperative complications, and to assess the impact of preoperative radiochemotherapy on postoperative hospital outcome. METHODS: From January 1990 to December 1998, 130 patients underwent oesophageal resection for malignancy. There were 103 males and 27 females (age: 61.3+/-11.5 years). Indications were squamous cell carcinoma in 69 patients and adenocarcinoma in 61. Preoperatively 30 patients (eight in stage IIB, 18 in stage III, and four in stage IV) received radiochemotherapy. There were 84 subtotal oesophagectomies, with anastomosis in the neck in 44 patients and at the thoracic inlet in 40, and 46 distal oesophageal resections. Digestive continuity was restored with the stomach in 92 patients (age: 63.4+/-10.2 years) and the colon in 38 (age: 52.3+/-12.8 years). With the exception of age (P<0.0001), there was no significant preoperative difference between gastric and colonic groups. RESULTS: Hospital mortality was 8.5% (11 patients), decreasing from 18.5% (before 1993) to 3.8% (since 1993). One patient (2.5%) died in the colonic graft group and ten (11%) in the gastric pull-up group (P=0.17). Postoperative complications occurred in 40 patients (31%), respectively, in ten (26%) and 30 (33%) patients after colonic and gastric transplants (P=0.48), and were pulmonary insufficiency or infection in 29 patients, anastomotic fistula in six, myocardial infarction in five, recurrent nerve palsy in four, renal insufficiency in three, and cerebrovascular accident in one. All fistulas occurred in the gastric pull-up group. The incidence of postoperative pulmonary complications was 70% (21/30 patients) in the subgroup who received preoperative radiochemotherapy, as compared to 11% (5/44 patients) in the subgroup of comparable staging, but without preoperative treatment (P<0.001). CONCLUSIONS: Colonic grafts are not associated with increased postoperative mortality or complications. Our results suggest that preoperative neoadjuvant treatment significantly increases postoperative pulmonary complications.

Chronic ischaemic gastritis: an unusual form of splanchnic vascular insufficiency.

Three cases of erosive gastroduodenitis secondary to chronic splanchnic vascular insufficiency are reported. In all cases, pain failed to respond to conventional therapeutic measures for peptic ulcer disease. A patchy discolouration and erythematous mottling of the gastric mucosa, with scattered shallow aphthous ulcers, was seen on endoscopic examination. Angiography showed coeliac axis involvement in all patients, with insufficient mesenteric collateral pathways. Chronic gastritis resolved clinically and endoscopically after revascularization.

Biology, physiology and physiopathology of clamping during liver surgery.

Liver surgery is currently performed with minimal morbidity and mortality, mostly thanks to reduced intraoperative blood loss, achievable by various types of liver clamping. A better knowledge of the physiological and physiopathological changes caused by liver clamping is however still necessary. The "natural" evolution of biochemical and liver function tests after liver surgery have been described. This paper describes the hemodynamic changes observed with different types of clamping and discusses several ways in which liver clamping techniques might be improved.

Combined liver-spleen-small intestine grafting in a rat model: role of transplanting additional lymphoid tissue on survival.

The aim of this study was to develop suitable models of combined intestinal grafting to examine the enhancing effect of intestinal grafting with additional lymphoid tissue using 30% of the liver mass and the whole spleen on recipient survival in the absence of immunosuppression. Grafts from DA (RT1a) rats were transplanted orthotopically to PVG (RT1(1)) recipients according to the following design: group 1 (n = 6), en bloc 30% liver/entire SB/spleen; group 2 (n = 7), en bloc 30% liver/SB; group 3 (n = 7), SB/spleen and group 4 (n = 7), SB control for the preceding groups. The orthotopic nature and proximal interposition of the SB graft allowed the assessment of protection afforded by components of the cluster on the SB graft using survival endpoints. Although group 4 hosts survived half as long compared to other groups, statistical significance was reached only in the case of group 1; group 1 MST equalled 15.3 days, significantly higher than group 4 (p = 0.01). Acute rejection was present in every grafted tissue and was equivalent whether liver was included or excluded in the cluster. GVHD was absent postoperatively using clinical or histological criteria; recipient spleens showed hyperplasia, donor spleens depicted lymphocytic depletion on histology. This study determined that statistically proven enhanced survival was obtained only after grafting 30% liver plus spleen with the entire SB. GVHD was rare in the fully allogeneic system despite transplanting a massive load of lymphoid tissue. The surgical models used in this study employing liver in the cluster, address the important question of how best to evaluate the role of heterotopic accessory liver grafting in providing tolerance to co-transplanted small intestine.

[Clinical value of positron emission tomography in the detection and staging of recurrent colorectal cancer]. / Intérêt clinique de la tomographie à émission de positons dans la détection et le bilan d'extension des récidives des cancers colorectaux.

BACKGROUND: Positron emission tomography (PET) has been shown useful for the staging of patients with various carcinomas. METHODS: We have applied this technique to 54 cases of colorectal carcinoma and compared it to conventional imaging techniques. RESULTS: PET had moderately higher sensitivity and specificity than conventional techniques to detect individual lesion sites (75% vs 70.8% and 63% vs 21% respectively). It detected the same number of patients with recurrences (35/39) but overestimated disease less frequently (5 cases vs 12). PET favorably influenced therapeutic management in 17 patients, indicating different or additional surgery in 9 while avoiding surgery with curative intent or unnecessary surgery in 8. In 5 cases, erroneous information provided by PET could be corrected by conventional imaging techniques. CONCLUSION: We conclude that PET appears to provide complementary information useful for staging patients with colorectal carcinomas. It can significantly modify patients management. These data should be confirmed by a prospective study.

Total intravenous anesthesia in South-African genetic porphyria (variegate porphyria).

The authors report the case of a female patient with South-African genetic porphyria who had to undergo hepatic tumorectomy under general anesthesia. The choice for propofol as the induction and maintenance agent using a balanced anesthetic technique led to a significant rise in urinary excretion of porphyrins without associated clinical manifestations. A short review of the literature on physiopathology of porphyrias and medicinal agents, susceptible to induce acute porphyric crisis follows. The authors conclude that the innocuity of propofol as induction and maintaining agent in the porphyric patient cannot be yet established without further studies.

[New philosophy in the treatment of peritoneal carcinomatosis of gastrointestinal origin]. / Philosophie nouvelle dans le traitement des carcinoses peritoneales d'origine digestive.

Cancer of the various organs of the abdominal cavity accounts for approximately 40% of yearly deaths in western countries. A frequently contributing factor is peritoneal carcinomatosis. The traditional approach to peritoneal carcinomatosis has been to renounce further surgical treatment, and resort to palliative chemotherapy. Tumour mass reduction by surgical debulking alone does not benefit the patient. Over the past decade, studies have shown that surgical debulking, (cytoreduction), combined with synchronous intraperitoneal chemotherapy provides good, and occasionally spectacular, results. The most significant results were initially obtained in the treatment of peritoneal pseudomyxoma and further studies have demonstrated the effectiveness of this combined approach in the treatment of colon, gastric and ovarian cancer. The statistical benefit gained by such treatment is thus far indiscutable. It should also be noted that the addition of perioperative hyperthermia appears to increase the effectiveness of treatment. While awaiting further options for the treatment of peritoneal carcinomatosis, notably in the arena of immuno- or genetic therapy, it is certain that combined cytoreduction/intraperitoneal chemotherapy/hyperthermia, is a feasible approach with proven benefit that should be included in current clinical protocols.

Fissure-in-ano, to divide or not to divide?

Anal fissure is one of the most common and painful proctological pathologies affecting mainly young individuals. The physiopathology in the development of a chronic anal fissure seems to be a combination of internal anal sphincter hypertonia and poor vascularization at the posterior midline. Treatment of acute fissures is conservative with supportive therapy, leading to healing in the majority of the patients. Open or closed lateral internal sphincterotomy is the treatment of choice for chronic anal fissures. In low pressure chronic fissures, sphincterotomy should be avoided and a V-Y island advancement flap may be an alternative procedure. Sphincterotomy can induce anal incontinence, a feared complication of this technique. Recent interest has developed in chemical sphincterotomy with local botulin toxin injections or glyceryl trinitrate application. Long-term follow-up is needed to evaluate these new therapeutic options.

Management of fulminant hepatic failure.

Fulminant hepatic failure is an infrequent but dreadful disease, occurring usually in young patients. Despite fulminant hepatic failure is reversible in most of the cases, some patients develop brain edema and intracranial hypertension, which are the most common cause of death in these patients. Liver transplantation significantly improves the prognosis of selected patients in who precise criteria predict a low chance of survival. This review summarizes the modern standard of care of patients with fulminant hepatic failure, with particular underlining of the management of brain oedema and intracranial hypertension.

[Leiomyosarcoma of the inferior vena cava: literature review and surgical treatment. Apropos of 2 retrohepatic localizations]. / Léiomyosarcome de la veine cave inférieure: revue de la littérature et traitement chirurgical. A propos de deux localisations rétrohépatiques.

Two cases of leiomyosarcoma of retrohepatic inferior vena cava are reported. The two patients are women and are currently alive with metastases one, seven years, and the other one year postoperatively. Leiomyosarcoma of inferior vena cava s a rare tumor which has an unexplained predilection for women. Clinical symptoms are non specific and depend mostly on the segment of the vessel involved. Preoperative diagnosis is based on ultrasonography, computed tomography and cavography. Although the prognosis is poor due to local recurrence and metastasis, we recommend an aggressive approach by radical tumor resection and caval reconstruction.

Pyogenic liver abscess. Diagnostic and therapeutic approach: a case report.

We report a case of liver abscess secondary to an asymptomatic, subacute appendicitis in a 51-year-old man. The general condition of the patient was altered but there were no gastrointestinal signs. Treatment consisted in broad-spectrum antibiotics, followed by surgical drainage of the abscess and appendicectomy.

Successful tricuspid valve replacement and pulmonary valvulotomy for carcinoid heart disease.

A case of successful tricuspid valve replacement with a mechanical prosthesis and pulmonary valvulotomy for carcinoid heart disease is reported. The patient was a 61 years old women. The primary tumor was in the terminal ileum. Liver metastasis and carcinoid syndrome were present since 8 years. After cardiac surgery, the patient survived 38 months and late death was related to disseminated metastasis. Even in case of metastasis, carcinoid tumor is slow growing. Without cardiac operation for correction of valvular lesions, terminal symptoms and death may often be related to cardiac operation for correction of valvular lesions, terminal symptoms and death may often be related to cardiac failure rather than to tumoral growth. Thus, even in presence of metastasis, cardiac surgery may be mandatory to improve both quality of life and survival.