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Biomedical subjects

Y Panis

Publications and source records attributed to Y Panis.

At least 55 records · Page 3Linked to original sources

Efficient suicide gene therapy of transduced and distant untransduced ovary tumors is correlated with significant increase of intratumoral T and NK cells.

Gene therapy using herpes simplex type 1 thymidine kinase gene (HSV1-TK) transfer followed by ganciclovir (GCV) treatment has revealed an important intratumoral and regional bystander effect that is at least partly immune-mediated. The aim of this work was to study the modifications of T lymphocyte subpopulations in a model of distant bystander effect occurring between ovary tumors. Bilateral ovarian tumors were generated in 21 WKY rats by injection in the ovarian pouch of either parental or HSV1-TK-expressing DWA-OC-1 ovarian cancer cells. After 14 days, rats were treated for two weeks with GCV (75 mg/kg x 2/d) or saline. All rats were killed at day 29 for pathological examination. The tumor-infiltrating mononuclear cells were analyzed by semi-quantitative immunohistochemistry. As compared to rats receiving saline, GCV-treated animals exhibited a complete disappearance of the HSV1-TK+ tumors with residual fibrotic scars (ovary weights: 0.46 +/- 0.4 g vs 10.11 +/- 1.5 g, P < 0.001). Interestingly, the contralateral HSV1-TK negative tumor showed a significant regression (12.39 +/- 1.93 g vs 22.24 +/- 237 g, P < 0.014). Furthermore, a lower incidence of tumoral ascitis was found in the GCV-receiving group (20% vs 90% P < 0.02). Within both TK- and TK+ tumors, there was a significant increase of CD4+, CD8+ and NK cells in the GCV-treated group compared to the saline-treated group. This study thus indicates that a distant bystander effect not only acts between close tumors within a given organ such as the liver, but also between more distant tumors in the peritoneal cavity. This effect is associated with significant infiltration of the tumor by immune system cells, supporting the notion that the distant bystander effect is immune-mediated.

Animals↗

Muscular contractile failure in septic patients: role of the inducible nitric oxide synthase pathway.

Skeletal muscle failure is a frequent manifestation of sepsis that affects prognosis and rehabilitation by impairing respiration and ambulation. Animal studies have shown that the inducible NO synthase (NOS2) is expressed in skeletal muscles during sepsis, likely affecting muscular function, by promoting the formation of the strong oxidant peroxynitrite. In contrast, whether human skeletal muscle expresses a functional NOS2 in similar conditions is unknown. We studied NOS2 expression (mRNA and protein) and activity and its role in contractile function in samples from rectus abdominis muscle obtained during surgical procedure in 16 septic patients and in 21 controls. Peroxynitrite formation was detected by immunohistochemical detection of nitrotyrosine residues. The main results of this study are as follows: (1) A significant increase in NOS2 mRNA, protein, and activity was found in muscles from septic patients, the expression of NOS2 protein positively correlating with sepsis severity. (2) Contractile force was significantly lower in septic than in control muscles. This phenomenon was not reverted by muscle incubation ex vivo with the NOS inhibitor L-NMMA, indicating that NO was not involved in force reduction at the time of biopsy. (3) NOS2 expression in skeletal myocytes was strongly co-localized with nitrotyrosine, revealing muscular peroxynitrite generation during the septic process, before the muscle was biopsied. Exposure of control muscles to an amount of peroxynitrite similar to that generated in septic muscles during the septic process resulted in a nonreversible reduction in force generation. These results suggest that NOS2 could be involved in the decreased muscular force of septic patients via the local generation of peroxynitrite.

Adult↗

[Laparoscopic surgery for benign colorectal diseases].

Since 1991 when the first cases of laparoscopic colectomy were reported, this technique has become widespread in colorectal surgery. Its reliability in colorectal cancer has been demonstrated but indications must still be limited to strictly controlled clinical trials that will determine its impact in terms of cancerology outcome. Inversely, for benign colorectal disease, the efficacy, low morbidity and the generally observed clinical benefit of laparoscopy compared with laparotomy, particularly in terms of patient comfort in the post-operative period and delay to normal activities, has been clearly demonstrated in several, though too often uncontrolled, trials. Laparoscopy will thus become more and more widespread and probably predominant for benign colorectal disease. Today, it is warranted to propose first-intention laparoscopic procedures for elective diverticulitis sigmoidectomy, for ileocecal resection for Crohn's disease, for derivation stomies, and finally, for surgical ablation of voluminous colonic polyps. In hands well trained in laparoscopic and colorectal surgery, laparoscopic procedures will be proposed in the near future for total colectomy, rectopexia, or even ileo-anal anastomosis.

Anal Canal↗

[Gene therapy of liver tumors].

Gene therapy is a new therapeutic option for liver tumors which has been evaluated in animal models. The liver has characteristic features particularly interesting for gene transfer. Because of the rapid tumor growth within a quiescent parenchyma, retroviral transfer could express selective tropism. Temporary anatomic vascular exclusion would allow selective perfusion of the liver and avoid extrahepatic diffusion of the gene therapy. The early results have been promising in the animal. Clinical studies are currently under way in patients with liver metastasis from colorectal cancer.

Adenoviridae↗

Liposomal encapsulation of ganciclovir enhances the efficacy of herpes simplex virus type 1 thymidine kinase suicide gene therapy against hepatic tumors in rats.

Suicide gene therapy based on ganciclovir (GCV) metabolism by transgene herpes simplex thymidine kinase (HSV-1 TK) has been used to selectively kill proliferating cells in clinical settings such as cancer, vascular restenosis, and immunological disorders. We investigated whether encapsulation of ganciclovir (GCV) into liposomes would improve its efficacy, especially against hepatic tumors. Large unilamellar liposomes containing GCV were prepared by reversed-phase evaporation. Pharmacokinetic studies in rats showed that, compared with free GCV, the intravenous injection of liposome-encapsulated GCV (lip-GCV) led to a faster decrease in GCV plasma concentrations, but higher liver-blood ratios. After treatment of syngeneic HSV-1 TK+ liver metastases in rats, histologically active tumors were found in 95% of the transplanted lesions when physiological saline had been given and in 50% when free GCV had been given at 90.2 microM/kg twice daily. This dose is known to be insufficient for the eradication of HSV-1 TK+ tumors. In contrast, only 5% viable tumors were found in rats receiving lip-GCV at this same concentration. Average tumor volumes were 19 +/- 15, 7 +/- 9, and <1 mm3 for the control, free GCV, and lip-GCV groups, respectively. GCV-related toxicity was no longer observed. The results demonstrate that liposomal encapsulation of GCV is feasible and significantly enhances its efficacy against HSV-1 TK+ hepatic tumors.

Animals↗

Plain abdominal radiography as a routine procedure for acute abdominal pain of the right lower quadrant: prospective evaluation.

The aim of this prospective study was to determine whether plain abdominal radiographs (PAX) are helpful in the management of adult patients presenting with acute pain of the right lower quadrant (RLQ). A questionnaire was filled in for each patient admitted to our hospital for acute abdominal pain of the RLQ, before and after PAX were obtained. The initial questionnaire indicated the suspected diagnosis and a provisional therapeutic option. A total of 104 consecutive patients were included in this study, 76 of whom underwent surgery. The negative laparotomy rate was 22%. PAX changed the suspected diagnosis and management for six patients (6%), leading in one case to negative laparotomy. Of the remaining five patients, three were operated (two for acute appendicitis and one for small bowel obstruction), and two were treated conservatively for ureteral calculi. This prospective study seems to demonstrate that the indiscriminate use of PAX is not helpful for most patients with acute pain of the RLQ. However, it may be performed in selected patients with clinically suspected small bowel obstruction or urinary symptoms.

Abdomen, Acute↗

Relation between cytogenetic characteristics of two human colonic adenocarcinoma cell lines and their ability to grow locally or metastasize or both: an experimental study in the nude mouse.

This study was aimed at elucidating the relation between the cytogenetic characteristics and the invasive ability of two human colonic adenocarcinoma cells lines, HT29 and CaCO2. These two cell lines have very different tumorigenic and metastatic capacities after intrasplenic injection into nude mice: high for HT29 and relatively weak for CaCO2. At the time of injection, cytogenetic studies of the two cell lines revealed shared abnormalities: paratriploidy with seven common extra chromosomes or chromosome regions and specific particularities. In HT29 cells, we observed a large marker of unknown origin, an isochromosome i(11)(q10) and 5, 12, 13, 15, 19, and (19q+) supernumerary chromosomes, and, finally, the absence of one chromosome 16. In CaCO2 cells, we observed a chromosome 1-derived marker with q24-31 duplication, 12q and 16 supernumerary chromosomes, and a der(16) marker. The most striking difference between the karyotypes of these two cell lines concerned chromosome 16 (under- and overexpressed in HT29 and CaCO2 cells, respectively), overexpression of chromosomes 13, 15, and 19 in HT29 cells, and the relative loss of 12p in CaCO2 cells. Although some differences may be due to the intrinsic characteristics of the stem line, the establishment of specific cytogenetic abnormalities points out the role of many regions of the genome in tumorigenic and metastatic capacities of malignant cells.

Adenocarcinoma↗

Surgical treatment of anoperineal Crohn's disease: can abdominoperineal resection be predicted?

BACKGROUND: Anoperineal Crohn's disease (APCD) runs an unpredictable course. Although this course is relatively benign in most patients, some will eventually require abdominoperineal resection (APR). The aim of this study was to identify prognostic factors of longterm APR in patients with APCD. STUDY DESIGN: From 1980 to 1996, 119 patients were operated on for APCD (mean +/- SD age 30 +/- 13 years; range 11 to 96 years). Patients were divided into two groups: those undergoing APR and patients without APR at the end of followup. The following prognostic criteria were studied: (1) age at onset of Crohn's disease (CD) and at the first manifestation of APCD, gender, APCD as the first manifestation of CD, and interval between the onset of CD and the first manifestation of APCD; (2) for the first manifestation of APCD, the type and number of lesions and the results of surgical treatment; and (3) associated intestinal localizations of CD and the type and number of manifestations of APCD during followup. RESULTS: Mean followup from the first manifestation of APCD was 93 months (range 1 to 398 months). At the end of followup, 30 patients had undergone APR (25%). Logistic regression analysis showed that four criteria seemed to be associated with an increased risk of APR: age at first APCD (p < 0.02), fistula as the first manifestation of APCD (p < 0.04), more than three APCD lesions during followup (p < 0.01), and rectal involvement by CD (p < 0.000001). When, as in eight patients, these criteria were all present, APR was performed during followup in 100% of patients. In the absence of all four criteria (eight patients), APR was never performed. CONCLUSIONS: This study allowed us to identify patients with APCD at high risk of APR. For these patients, early prevention of CD recurrence should be attempted by aggressive medical therapy.

Adolescent↗

Management of anastomotic leakage after nondiverted large bowel resection.

BACKGROUND: The purpose of this study was to determine the natural history of anastomotic leakage after elective colorectal resection and supraperitoneal anastomosis without temporary stoma. STUDY DESIGN: Medical records from 1990 to 1997 were studied; 655 consecutive patients underwent colonic or rectal resection (without stoma). Patients were divided into two groups: those with clinical anastomotic leakage confirmed by laparotomy (group 1) and those without anastomotic leakage (group 2). Postoperative clinical and biologic findings were compared between the two groups. RESULTS: Anastomotic leakage occurred in 39 of 655 patients (6%). Clinically suspected anastomotic leakage was only confirmed by contrast radiography in 13 of 24 patients (54%), and by CT in 8 of 9 patients (89%). Significantly more patients in group 1 than group 2 had the following: fever (> 38 degrees C) on day 2 (p < 0.001); absence of bowel action on day 4 (p < 0.001); diarrhea before day 7 (p < 0.001); collection of more than 400 mL of fluid through abdominal drains from day 0 to day 3 (p < 0.01); renal failure on day 3 (p < 0.02); and leukocytosis after day 7 (p < 0.02). Among the 39 patients in group 1, 28 (71%) had at least one of these clinical or biologic manifestations before day 5, but the mean delay for reoperation was only 8 days. The combination of signs observed before day 5 was associated with an increased risk of anastomotic leakage, from 18% with two signs to 67% with three signs. Overall mortality rate was 2% (13 of 655) and was significantly higher in group 1 than group 2: 5 of 39 (13%) versus 8 of 616 (1%, p < 0.001). In patients with anastomotic leakage, death occurred in 5 of 23 patients (22%) reoperated on after day 5, versus 0 of 11 patients (0%) reoperated on before day 5 (NS). Univariate analysis showed that three clinical characteristics were associated with a significantly high risk of mortality after reoperation for anastomotic leakage: age greater than 65 years (p < 0.01), American Anesthesiologist Association score greater than 3 (p < 0.05), and blood transfusions during the first operation (p < 0.02). CONCLUSIONS: In our study, some postoperative clinical and biologic signs were associated with a higher risk of anastomotic leakage. The knowledge of these findings might help in the early diagnosis and management of patients with anastomotic leakage after large bowel resection.

Anastomosis, Surgical↗

Optimal duration of urinary drainage after rectal resection: a randomized controlled trial.

BACKGROUND: Voiding dysfunction is frequently observed after rectal resection and justifies urinary drainage. However, there is no agreement about the optimal duration of this postoperative drainage. The aim of this controlled trial was to compare 1 versus 5 days of transurethral catheterization after rectal resection, with special reference to urinary tract infection and bladder retention. METHODS: One hundred twenty-six patients undergoing rectal resection were included in a prospective randomized study designed to compare the results for patients undergoing 1 day of transurethral catheterization after rectal resection (1-day group) with those for patients undergoing 5 days' catheterization (5-day group). RESULTS: Patients were randomly assigned to the 1-day and 5-day groups (n = 64 and 62, respectively). Clinical findings and surgical procedures were comparable in both groups. Acute urinary retention occurred in 16 patients (25%) in the 1-day group versus 6 (10%) in the 5-day group (P < .05). Urinary tract infection was observed in 13 of 64 patients (20%) in the 1-day group versus 26 of 62 (42%) in the 5-day group (P < .01). Multivariate analysis revealed that after 1 day of catheterization carcinoma of the low rectum and lymph node metastasis were significant risk factors for acute urinary retention (P < .05 for both factors). After selection of patients without low rectum carcinoma, the acute urinary retention rate was comparable in both groups (14% in the 1-day group versus 7% in the 5-day group), but the urinary tract infection rate was significantly lower in the 1-day group versus the 5-day group (14% vs 40, P < .01). CONCLUSIONS: Our controlled study showed that after rectal resection 1 day of urinary drainage can be recommended for most patients. Five-day drainage should be reserved for patients with low rectal carcinoma.

Aged↗

[Three cases of diverticular perforation of the caecum and ascending colon].

Perforation of the ascending colon secondary to diverticulitis is an uncommon surgical emergency. It is usually diagnosed during exploratory laparotomy for suspected appendicitis. We report three cases of cecal perforation due to diverticulitis. Imaging work-up, especially computed tomography can establish the preoperative diagnosis of cecal diverticulitis and guide its management.

Adult↗

[Preoperative evaluation of gastric adenocarcinomas: comparison of CT results with surgical and patholgic results].

PURPOSE: The objective of our study was to reassess the value of CT scan in the preoperative evaluation of gastric adenocarcinoma, using surgical and pathologic findings as the reference standard. MATERIALS AND METHODS: Forty-five patients who had preoperative CT scan for gastric carcinoma were retrospectively included in the study. Images were analyzed by two readers working in consensus with respect to tumor detection, tumor location, depth of invasion, involvement of adjacent organs, lymph node involvement and presence of peritoneal carcinomatosis. RESULTS: Gastric tumor was visible in 91% of cases. Accurate tumor localization was obtained in 50% of cases. Depth of tumor penetration was correctly evaluated in 40% of the cases. Evaluation of regional and distant lymph node metastases was correct in 54% and 64% of cases, respectively. Peritoneal carcinomatosis was depicted in 17% of cases. CONCLUSION: CT scan allows detection of gastric adenocarcinoma in the majority of cases. However, this technique markedly underscores the extent of gastric adenocarcinoma. Therefore, CT scan should not be used to determine the preoperative staging of gastric adenocarcinoma.

Adenocarcinoma↗

[Hepatic brucelloma: 2 cases and a review of the literature].

We report two new cases of hepatic brucelloma in addition to the 22 previously reported cases in the literature. Our analysis of these cases reveals certain characteristics. Hepatic brucelloma is a rare localization that follows previously undetected acute brucellosis. Brucelloma is a result of caseification of a granulomatous reaction induced by persistent Brucella in macrophages. Clinical manifestations can mimic malignant liver tumors or pyogenic, amebic liver abscess. Diagnosis is based on the association of characteristic imaging features (central calcification and peripheral necrotic areas), positive serology and hepatic granulomas. Brucella is rarely isolated in the blood or liver. Awareness of this clinical variant can prevent unnecessary laparotomy. Treatment should begin with rifampicine (900 mg per day) and doxycyclin (200 mg per day) for 3 months. If medical treatment is unsuccessful, percutaneous or surgical drainage should be performed. A cure should be achieved in all cases.

Anti-Bacterial Agents↗

[Surgical treatment of hemorrhagic proctocolitis].

Surgical treatment of chronic ulcerative colitis requires restorative proctocolectomy with ilial pouch-anal anastomosis to remove all the disease bowel and provide cure. A one-stage or two-stage procedure can be performed after subtotal colectomy with ileostomy and colostomy. Restorative proctocolectomy is not advised for very old patients or patients with anal sphincter insufficiency. In such cases, total colectomy with ileo-rectal anastomosis is proposed. The rectal stump must be examined regularly by rectoscopy because of the risk of cancer. A proctocolectomy with definitive ileostomy is proposed after pouch-anal excision for pelvic septic complications (5% of ileal pouch-anal anastomoses). Surgical treatment of chronic ulcerative colitis is indicated when medical treatment fails, at onset of fulminant acute colitis, or because of colorectal dysplasia.

Aged↗