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P Gervaz

Publications and source records attributed to P Gervaz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Converted laparoscopic colorectal surgery.

BACKGROUND: Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial. METHODS: A comprehensive search of the English-language literature was updated until May 1999. RESULTS: Twenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088), diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald chi-square value, p < 0.001). CONCLUSIONS: In nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.

Aged↗
PubMed2001

Quantitative short-term study of anal sphincter function after chemoradiation for rectal cancer.

HYPOTHESIS: Pelvic irradiation adversely affects anal sphincter function after proctectomy with coloanal anastomosis for low rectal and middle rectal (<10 cm from the anal verge) tumors. DESIGN: Case-control study. SETTING: Private, tertiary care referral center. PATIENTS: Patients treated for low rectal adenocarcinoma between January 1, 1994, and October 31, 1999. INTERVENTIONS: Anal manometric data were prospectively collected at the time of initial diagnosis and before ileostomy closure. MAIN OUTCOME MEASURES: Mean and maximum resting pressures (RPs) and squeeze pressures, threshold volume for sensation, and maximal tolerable volume. RESULTS: Twenty-three patients in the surgery group and 19 in the chemoradiotherapy group were considered for analysis; 15 patients had preoperative radiotherapy and 4 had postoperative radiotherapy. At the time of ileostomy closure, RPs were significantly lower in the chemoradiotherapy group than in the surgery group (32.7 +/- 17 vs 45.3 +/- 18 mm Hg; P =.03). Squeeze pressures were not significantly different between the surgery and chemoradiotherapy groups (108.7 +/- 56.7 vs 102.0 +/- 52.6 mm Hg; P =.69). The ratios of postresection to preresection RPs were also significantly lower in the chemoradiotherapy group (0.49 +/- 0.29) than in the surgery group (0.76 +/- 0.22) (P =.005). Eight to 12 weeks after proctectomy with coloanal anastomosis, a 24% decrease in RP was noted in the surgery group. The addition of adjuvant pelvic irradiation decreased RP by another 27%. CONCLUSION: Adequate shielding of the anal sphincter should be performed for low rectal cancers whenever a sphincter-preserving procedure is considered.

Adenocarcinoma↗
PubMed2001

Colonic J-pouch function in rectal cancer patients: impact of adjuvant chemoradiotherapy.

PURPOSE: The colonic J-pouch technique of reconstruction optimizes functional outcome after proctectomy with coloanal anastomosis. However, the impact of adjuvant chemoradiation therapy on pouch function in rectal cancer patients has not been investigated. METHODS: From January 1994 to December 1999, 74 patients with midrectal or low rectal tumors (less than 10 cm from the anal verge) underwent a proctectomy with coloanal anastomosis with colonic J-pouch reconstruction. Chemoradiation was offered in patients with Stage II and III disease. Radiation therapy was administered using a four-field technique including the anal canal, for a total dose of 50.4 Gy (1.8 Gy/fraction/day). Fifteen patients (20 percent) died with metastatic disease, five (6.8 percent) died of other causes without evidence of recurrence, and five (6.8 percent) were lost to follow-up. In addition, two patients had local recurrence (2.7 percent) at the time of follow-up. Forty-five of 47 eligible patients (96 percent) responded to a questionnaire designed to evaluate specifically the degree of continence and pouch evacuation. RESULTS: The mean age of patients was 68.9 (range, 42-88) years and the mean duration of follow-up was 28.8 (range, 1-69) months. There were 28 patients in the surgery alone group and 17 patients who received either preoperative (13) or postoperative (4) adjuvant chemoradiation therapy. Patients in the surgery alone group had a significantly better degree of continence (mean +/- standard deviation continence score: 18.1 +/- 2.9 vs. 13.3 +/- 4.1, P < 0.001) and were less likely to experience evacuatory problems (mean +/- standard deviation evacuation score: 21.3 +/- 3.7 vs. 16.4 +/- 3.5, P < 0.001). Use of a pad was more frequent in the chemoradiation therapy than in the surgery alone group (53 vs. 18 percent, P = 0.02). The incidence after functional disorders was also more frequent in the irradiated group of patients: incontinence to gas (76 vs. 43 percent, P = 0.03), to liquid stool (64 vs. 25 percent, P = 0.01), and to solid stool (47 vs. 11 percent, P = 0.01). Moreover, irradiated patients reported more frequent pouch-related specific problems, such as clustering (82 vs. 32 percent, P = 0.001), and sensation of incomplete evacuation (82 vs. 32 percent, P = 0.001). Finally, regression analysis demonstrated that radiation-induced sphincter dysfunction was progressive over time. CONCLUSIONS: Both preoperative and postoperative chemoradiation therapy adversely affects continence and evacuation in patients with colonic J-pouch. Because radiation-induced damage to the normal tissues is known to be cumulative over time, long-term progressive dysfunction of the anal sphincter and neorectum are causes of concern. Consideration should be given to excluding the anal canal from the field of irradiation in patients with Stage II and III rectal cancer, whenever a sphincter-preserving procedure is planned.

Adult↗
PubMed2001

Loss of heterozygosity and HIV infection in patients with anal squamous-cell carcinoma.

PURPOSE: This study was designed to determine whether loss of heterozygosity and/or microsatellite instability correlate with HIV infection and tumor recurrence after chemoradiation therapy in patients with squamous-cell carcinoma of the anus. BACKGROUND: The molecular mechanisms leading to the progression of HIV-related squamous-cell carcinoma of the anus are poorly understood. In particular, genetic alterations responsible for resistance to chemoradiation have important clinical and functional implications. METHODS: In a case-control study, we analyzed normal and tumor DNA samples of four patients with squamous-cell carcinoma of the anus who were successfully treated with chemoradiotherapy and four patients with radio-resistant squamous-cell carcinoma of the anus who required abdominoperineal resection for local recurrence. To determine the presence of microsatellite instability, we used the reference panel of five pairs of microsatellite primers recommended for colorectal cancer specimens. These include the microsatellite markers BAT25, BAT26, D5S346 (APC), D2S123 (hMSH2), and D17S250 (P53). In addition, we used microsatellite markers for loss of heterozygosity analyses that were tightly linked to tumor suppressor genes. These included D3S1611 (hMLH1), D17S513 (P53), D18S46 and 18qTA (DCC/SMAD4), D5S107 (APC), and CA5 (hMSH2). RESULTS: There were two HIV-positive and two HIV-negative patients in each group. Three HIV-positive patients (one in the chemoradiotherapy group and two in the nonchemoradiotherapy group) demonstrated loss of heterozygosity. In the chemoradiotherapy group, one HIV-positive patient demonstrated loss of heterozygosity at the hMLH1 locus. In the nonchemoradiotherapy group, two HIV-positive patients exhibited a total of four instances of loss of heterozygosity. One tumor had loss of heterozygosity at hMSH2 and DCC/SMAD4; another tumor demonstrated loss of heterozygosity at hMSH2 and APC. Microsatellite instability-low was found in two HIV-positive patients. No instances of loss of heterozygosity and microsatellite instability were detected in HIV-negative patients. CONCLUSION: Loss of heterozygosity and microsatellite instability, which reflect inactivation of tumor-suppressor genes and genomic instability, occur with increased frequency in HIV-associated squamous-cell carcinoma. These data demonstrate for the first time evidence of loss of heterozygosity at the APC and DCC/SMAD4 gene loci in anal carcinoma. Although the findings presented here need to be expanded in a larger study, the recurrent loss of heterozygosity at D2S123, which was demonstrated in HIV-positive patients with radio-resistant squamous-cell carcinoma of the anus, is notable.

Adult↗
PubMed2001

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Adenocarcinoma↗
PubMed2001

The efficacy of chemoradiation therapy in HIV seropositive patients with squamous cell carcinoma of the anus.

OBJECTIVE: The aim was to assess the efficacy of chemoradiation therapy for squamous cell carcinoma of the anal canal in HIV seropositive patients. PATIENTS AND METHODS: A retrospective review of all patients with squamous cell carcinoma of the anus treated primarily with combined chemotherapy (5-fluorouracil and mitomycin) and radiotherapy or local excision was undertaken comparing HIV seropositive to HIV seronegative patients. RESULTS: Thirteen HIV seronegative patients were compared with 6 HIV seropositive patients. The HIV positive group included a higher proportion of males and a significantly greater history of prior treatment for condyloma. There was no difference in the median radiation dose (5020 cGy vs 4500 cGy, P=0.10). There was a trend towards higher local tumour recurrence in the HIV seropositive patients although this was not statistically significant (30% vs 66%). The CD4 count of HIV positive patients did not correlate either with their ability to complete the prescribed treatment regimen or with subsequent recurrence. CONCLUSION: Combined chemoradiation is feasible in HIV positive patients, however, local recurrence rates in HIV positive patients may be higher. Tolerance of this therapy in HIV seropositive patients or recurrence after therapy are not related to the patient's CD4 cell count.

Journal Article↗
PubMed2000

Effect of previous surgery on abdominal opening time.

PURPOSE: The purpose of this study was to document prospectively the time required to gain access to the abdomen to perform a planned procedure in patients with and without previous surgery. METHODS: Patients were obtained from the consecutive cases of 11 surgeons at three colorectal surgery centers. Opening time (skin incision to retractor placement) was measured and recorded in the operating room by the circulating nurse or by an independent researcher. Demographic data including the number and type of previous operations and the presence and severity of adhesions were recorded by the staff surgeon. A comparison of opening times between patients with and without previous abdominal operations was conducted. RESULTS: One hundred ninety-eight patients had abdominal operations. Fifty-five percent had previous abdominal procedures. Patients with prior surgery required a mean of 21 minutes to open their abdomens, whereas patients without prior surgery required a mean of 6 minutes (P < 0.01). The median times were 17 and 6 minutes, respectively. Eighty-three percent of patients with prior surgery had adhesions, whereas only 7 percent of patients had adhesions on their initial operation. Patients with prior surgery also had higher grade adhesions (P < 0.001). Irrespective of previous surgery, comparing patients with adhesions with those without, patients with adhesions required a mean of 22 minutes to open, whereas the lack of adhesions resulted in a mean opening time of 6 minutes. CONCLUSIONS: Previous surgery and the presence of adhesions add significant time to opening the abdomen.

Abdomen↗
PubMed2000

Angiogenesis of liver metastases: role of sinusoidal endothelial cells.

PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from pre-existing blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells are involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in BD IX rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal antibody. RESULTS: In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histological differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 microm, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.

Animals↗
PubMed2000

p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer.

Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.

Adenocarcinoma↗
PubMed2000

Growth inhibition of liver metastases by the anti-angiogenic drug TNP-470.

OBJECTIVE: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP-470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. BACKGROUND: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP-470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti-angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. METHODS: 10(7) DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP-470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti-von Willebrand Factor monoclonal antibody. RESULTS: In vitro, TNP-470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC50 of 0.1 microg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm3 vs 406 mm3, p=0.03) were significantly reduced in the TNP-470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/x200 field, p=0.41). CONCLUSION: TNP-470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti-angiogenic and direct cytotoxic effects.

Angiogenesis Inhibitors↗
PubMed2000

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).

Carcinoembryonic Antigen↗
PubMed2000

Permanent access to the portal vein in rats: an experimental model.

A safe and reproducible method for placement of indwelling catheters into the portal venous system is a prerequisite for improved delivery of anticancer drugs to experimental liver metastases. Due to the lack of tumor models in large animals and the difficulty in establishing permanent access to the portal vein in rodents, this type of model has rarely been described in the laboratory setting. We propose a simple, minimally invasive method for repeated portal vein injections in rats. A vascular access device was used, which remained patent for periods of up to 3 months. Placement and support of the catheter tip in the portal vein was performed with a technique designed to avoid portal thrombosis and infections. Permanent portal vein access in a rodent model of liver metastases will be invaluable for the development of novel therapeutic strategies.

Animals↗
PubMed1998

Therapeutic potential of the anti-angiogenesis drug TNP-470.

Neovessel formation is a pre-requisite for tumour growth and dissemination. Inhibition of angiogenesis is a promising approach for the treatment of neoplasms. In recent years, antiangiogenic drugs, such as TNP-470, have entered clinical trials. In this paper, we review the key experimental and clinical data on the role of TNP-470 in anti-tumour treatment.

Animals↗
PubMed1997

Glutaraldehyde-tanned bovine carotid artery graft for infrainguinal vascular reconstruction: 5-year follow-up.

OBJECTIVE: To assess the long-term patency of a modified biological conduit, the glutaraldehyde-tanned bovine carotid artery, in above-knee infrainguinal arterial reconstruction. PATIENTS AND METHODS: Prospective follow-up of a cohort of 58 above-knee femoropopliteal grafts in 55 patients. Graft patency was assessed at yearly intervals with doppler ankle pressure measurements. RESULTS: The median follow-up period has been 67 months. Nine grafts occluded within 30 days of surgery and a further 19 graft closures have been observed in the follow-up period. The overall cumulative primary graft patency at 1, 3 and 5 years was 70%, 61% and 56%, respectively. If the 30-day graft failures are excluded, the primary graft patency rises to 83%, 74% and 68% at 1, 3 and 5 years, respectively. Six limbs have been amputated, four above the knee and two below the knee. There were no graft aneurysms and no graft infections. CONCLUSION: Results indicate that the modified bovine carotid artery graft with an above-knee anastomosis does not seem to be inferior to PTFE, but is inferior to reversed vein. Modified biological conduits offer a reasonable alternative to synthetic grafts for infrainguinal arterial reconstruction and appear to maintain acceptable long-term mechanical stability.

Aged↗
PubMed1993

[Metastatic tumors of unknown origin: when can intervention be justified?].

Cancer of unknown primary site is a common clinical entity, accounting for 5% of all cancer patients. The diagnostic evaluation of these patients must permit to exclude treatable tumors. We reviewed the charts of 85 patients admitted with this diagnostic. We propose an algorithm for investigation of these patients.

Adult↗