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Biomedical subjects

M A Reymond

Publications and source records attributed to M A Reymond.

At least 19 recordsLinked to original sources

DCC protein as a predictor of distant metastases after curative surgery for rectal cancer.

PURPOSE: The aim of this study was to determine the value of DCC (deleted in colorectal cancer) protein for predicting metachronous distant metastases after curative surgery for rectal cancer. The DCC protein--for which a gene has been located on chromosome 18q--has recently been reported to have a prognostic value in colorectal cancer. This finding might have implications for treatment of International Union Against Cancer Stage II rectal carcinoma, in which distant metastases will develop in 14 percent of patients despite optimal surgery. METHODS: Paraffin-embedded tissues from 85 patients who developed distant metastases, but no local recurrence, after curative surgery for rectal cancer were matched with 85 samples from patients who remained disease-free. Matching criteria were tumor stage, age, gender, and date of surgery. Expression of DCC protein was assessed using immunohistochemistry. End points of follow-up were recurrence of disease and death. Mean follow-up was 9.6 years. No patient received either local or systemic adjuvant therapy. RESULTS: The DCC protein was found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC protein had an negative influence on survival (P = 0.03). For all tumor stages together, sensitivity of the test for subsequent occurrence of distant metastases was 42 percent and specificity was 71 percent. In Stage II cancers, the positive predictive value was 19 percent, and the negative predictive value was 88 percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic marker in patients with rectal carcinomas, but the positive predictive value of DCC protein for occurrence of metachronous metastases does not appear to be sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.

Biomarkers, Tumor

Early results of a prospective multicenter study on 500 consecutive cases of laparoscopic colorectal surgery. Laparoscopic Colorectal Surgery Study Group (LCSSG).

BACKGROUND: Prospective randomized multicenter studies comparing laparoscopic with open colorectal surgery are not yet available. Reliable data from prospective multicenter studies involving consecutive patients are also lacking. On the basis of the personal caseloads of specialized surgeons or of retrospective analyses, it is difficult to judge the true effectiveness of this new technique. This study aims to investigate the results of laparoscopic colorectal surgery in consecutive patients operated on by unselected surgeons. METHODS: This observational study was begun August 1, 1995, in the German-speaking part of Europe (Germany and Austria) and 43 centers initially agreed to participate. All consecutive cases were documented. All data were rendered anonymous. Analysis was performed on an intention-to-treat basis. The study committee was blinded to the participating center. RESULTS: By the end of the 1st year, 500 patients (M:F ratio 0.83, mean age 62.9 years) had been treated by 18 centers; 269 operations were performed for benign indications and 231 for cancer (palliative and curative). Most operations were done on the distal colon or rectum. An anastomosis was performed in 84%, with an overall leakage rate of 5.3% (colon 3.6% and rectum 11.8%), which required surgical reintervention in 1.7%. The mean operating time was 176 min and showed a decreasing tendency over the period under study. The conversion rate was 7.0% and the overall complication rate 21.4%. The reoperation rate was 6.6%; the most common cause was bleeding. There was one ureteral lesion (0.2%), but urinary tract infections were fairly common (4.8%). A postoperative pneumonia was diagnosed in 1.6% of the cases. No thromboembolic complications were reported. The 30-day mortality rate was 1.4% and overall hospital mortality 1.8%. CONCLUSIONS: Laparoscopic colorectal operations are still rare (about 1% of all colorectal operations in Germany). Laparoscopic procedures are more common on the left colon and rectum than on the right colon. The surgical complication rate is acceptable, comparable with rates reported by others for open surgery. Cardiopulmonary and thromboembolic complications were rarely seen. Mortality and surgical morbidity rates do not differ significantly among participating centers. A learning curve, reflected by a shortening of the operating time and a somewhat lower conversion rate, was observed over the observation period.

Aged

Influence of surgery on metachronous distant metastases and survival in rectal cancer.

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.

Adult

Analysis of differential gene expression in human colorectal tumor tissues by RNA arbitrarily primed-PCR: a technical assessment.

RNA arbitrarily primed (RAP)-PCR is a powerful tool for studying differential gene expression in cancer cells. Systematic analysis of human tumor samples may provide a list of markers with potential application to the diagnosis, prognostic assessment, and treatment of the disease. Nevertheless, because of characteristics inherent to the samples and technique, artifactual results are likely. We have assessed the effects of several factors on RAP-PCR performance to determine the sensitivity and reproducibility of the technique, as well as the accuracy of its results, under different conditions in human cell lines and in a series of 129 paired human normal colonic mucosa-colorectal carcinoma samples. Our results show that RAP-PCR provides reliable fingerprints in a relatively wide spectrum of circumstances, including variations in RNA concentration and contamination by DNA. Densitometric analysis indicated that relative band-intensity variations more than 20% were reproducible in 95% of the cases. Serial analysis of paired normal-tumor cases yielded a number of bands that were recurrently either underexpressed or overexpressed in tumor relative to normal mucosa. These differentially expressed bands are prime targets of research because they represent candidate tumor-specific up- or down-regulated genes with a relevant role in carcinogenesis.

Colorectal Neoplasms

Standardized characterization of gene expression in human colorectal epithelium by two-dimensional electrophoresis.

New diagnostic and prognostic markers are needed in colorectal cancer. They can be found by differential analysis at DNA, RNA or protein level. The accuracy of phenotypic comparisons of tumor and normal tissues depends on the purity of the samples. We present an effective method to identify and isolate proteins that are differentially expressed under altered conditions, and a two-dimensional reference protein map of the normal human colonic epithelium. Normal colonic mucosa, primary tumors and liver metastases were prepared in the operating room. After washing in an ice-cold medium containing protease inhibitors, crypts were isolated by mechanical preparation without using metalloproteinases. Epithelial cells were then selected using Ber-EP4 Dynabeads. The samples were denaturated before processing for immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis according to SWISS-2DPAGE standards. The samples contained more than 95% epithelial cells as confirmed by fluorescence-activated cell sorting using pan-anticytokeratin antibodies. Cell surfaces were not damaged, as assessed by scanning electronic microscope. A protein reference map of the normal colonic epithelium was defined. Using gel matching, N-terminal sequencing and/or immunoblotting techniques, 60 polypeptides - including proteins specifically expressed in colorectal epithelium - have now been identified. This reproducible method of sample preparation permits the comparison of protein patterns found in various pathological states with the present reference map (http://www.expasy.ch). Some of these patterns might provide diagnostic or prognostic markers, or even molecular targets for therapy in the future.

Colorectal Neoplasms

[Errors and risks in oncologic laparoscopic surgery].

Oncological problems associated with laparoscopic colorectal surgery with curative intent include port site metastases, inadequate radicality, seeding of tumour cells through unprotected recovery of the surgical specimen, faulty surgical technique, and failure to observe the technical and/or oncological limitations applicable to certain tumour sites. Investigations so far reported reveal a preponderance of mechanical pathogenesis of port site metastases caused by the contamination of trocar entry ports by tumour cells borne on instruments, trocars and resected material. This suggests that appropriate precautionary measures could resolve the problem. It appears that the CO2 pneumoperitoneum plays only a minor role in the development of port site metastases. Owing to a lack of long-term data, the oncological radicality of laparosopic resections for colorectal carcinoma cannot be assessed; merely a few reports on the number of lymph nodes removed during such operations have been published. Nevertheless, it would appear that fewer lymph nodes were removed than with comparable conventional surgery. However, a more accurate analysis needs to take account of the fact that the indication for laparoscopic surgery is determined by the size and location of the tumour. The many potential pitfalls and hazards of oncological laparoscopic surgery make it mandatory that such interventions should be done only within the framework of prospective clinical studies covering limited indications. Randomized prospective studies to cover all tumour stages and sites cannot be recommended.

Abdominal Muscles

The incidence of port-site metastases might be reduced.

BACKGROUND: Laparoscopic resection for cancer is controversial and port-site metastases are not infrequent. The mechanisms of occurrence of port-site metastases remain unclear. Animal experiments have suggested a role for carbon dioxide (CO2), but port-site metastases also occur after thoracoscopy, where no CO2 is used. The aim of this study was to define the role of CO2 in the seeding of tumor cells in the human patient. METHODS: CO2, instruments, trocars, suction device, and peritoneal washing were examined during 12 staging laparoscopies for pancreatic cancer. The presence, viability, and biological significance of cells were investigated using conventional cytology, polymerase chain reaction (PCR), and restriction fragment length polymorphisms (RFLPs) to detect the presence of a mutant k-ras gene as a genetic marker of cancer cells. RESULTS: Cytology exam of peritoneal washing, instruments, the suction device, and trocars revealed many cells. Tumor cells were detected in 6/12 peritoneal, in 4/12 trocars and 4/11 instruments washings, but not in 12 CO2 samples. The DNA content of CO2 was very low-as assessed by PCR. Mutant DNA was detected by RFLP in four out of 12 aerosols. Six aerosols did not contain any DNA. Two aerosols were borderline. CONCLUSIONS: During staging laparoscopy for pancreatic cancer in humans, CO2 contains only very low levels of free-floating tumor cells, even in the presence of massive peritoneal contamination. These results suggest that the incidence of port-site metastases might be reduced if mechanical contamination of the port sites with instruments or with the specimen can be avoided.

Adenocarcinoma

[Extraction of cystic duct occlusion calculus in laparoscopic cholecystectomy].

Occluding stones left in the stumpf of the cystic duct may account for between 17% and 25% of the cases of post-cholecystectomy syndrome. When acutely inflamed or empyemic gallbladders are removed, an occlusive cystic duct stone must almost always be expected. When performing laparoscopic cholecystectomy, therefore, care must be taken to ensure that any stone occluding the cystic duct are detected and removed. After completely freeing the cystic duct to the point of its junction with the common bile duct, it is carefully "palpated" with a 5 mm forceps for the presence of stones. Any such present are pressed out of the duct through a transverse incision, and retrieved. Bile reflux through the incision in the duct indicates freedom from stones. Finally, intraoperative cholangiography can be performed.

Cholangiography

[Pathogenesis of puncture-site metastases after laparoscopy].

The major factor underlying the seeding of tumor cells during laparoscopy are mechanical, with CO2 playing only a secondary role. The peritoneal wound is of great importance, especially in advanced tumor stages, when cells are present within the abdominal cavity. Most reported port-site metastases were found within the extraction port when no protective measures were taken. Gasless laparoscopy is no solution to the problem, since numerous port-site metastases have been described after thoracoscopy, during which no CO2 is used. The surgeon's role in the seeding of tumor cells is based on tumor perforation, excessive manipulation and replacement of trocars. This presumably explains the large differences (0 and 21%) in the reported incidence of port-site metastases. Prospective studies now show that it is possible to keep the incidence of abdominal wall metastases to about 1%-which is comparable with that seen in open surgery-by the use of a meticulous operating technique and preventive measures.

Animals

[Controlling complications in laparoscopic cholecystectomy: diffuse parenchyma hemorrhage in the liver parenchyma].

The inflammatory pericholecystic reaction to acute or subacute cholecystitis results in the involvement in the inflammatory process of connective tissue within the liver bed, with subsequent neovascularization. The inflamed wall of the gallbladder and the surrounding connective tissue also involved in the inflammatory process become fused together thus preventing dissection in this plane. As a result, the gallbladder affected by acute cholecystitis frequently has to be dissected directly out of the liver parenchyma. The resulting diffuse parenchymal bleeding proves difficult to control by cauterization. In addition, there is a danger of postoperative bile leakage occurring. Today, the use of fibrin sealing is accepted practice in the treatment of oozing haemorrhage from the resection surface of the liver following resective surgery, and for the prevention of postoperative biliary fistulae. Using special application systems, the two-component fibrin sealing can now also be employed under video-endoscopic control. Through direct application of the adhesive to the parenchyma in the liver bed using a flexible catheter, diffuse oozing bleeds can be effectively arrested. In addition, coagulation-related parenchymal necroses associated with the development of biliary fistulae can be avoided. The technique of video-endoscopic controlled fibrin sealing is an important method of preventing and controlling complications arising during video-endoscopic surgery.

Cholecystectomy, Laparoscopic

[Laparoscopic cholecystectomy in antegrade (prograde) technique].

In the case of acute cholecystitis and chronic cholecystitis of lang standing, the inflammatory changes in Calot's triangle make the risk of damaging the bile duct during laparoscopic cholecystectomy particularly high. In view of the difficult anatomical situation in Calot's triangle, such patho-anatomical conditions when encountered during open surgery best dealt with by anterograde (prograde) dissection of the gallbladder beginning from the fundus and proceeding towards the neck of the gallbladder. Since this approach is considered to be safer and less risky, it should also be adopted during laparoscopic surgery. The advantage is to be seen in the initial dissection far removed from the bile ducts. Despite pronounced inflammatory changes and initial preservation of the cystic artery, the use of modern technologies permit a virtually bloodless procedure. Nevertheless, the difficult anatomical situation makes a high level of readiness to conver mandatory. Should there be any doubt, the open surgical approach is the safer modality.

Cholecystectomy, Laparoscopic

[Suture of trocar puncture sites after laparoscopy].

The suturing of port sites measuring at least 10 mm in diameter following laparoscopy can prevent the incarceration of small bowel and/or omentum and scar hernias. This means that all port sites remaining after using trocars of at least 10 mm need to be carefully closed by suturing. In the case of oncological procedures in particular, it is important to ensure that the bite of the suture needle includes the peritoneum, to avoid leaving a fresh peritoneal wound offering favourable conditions for the implantation of tumour cells. The technique described here for port site suturing involves all the layers of the abdominal wall, including the peritoneum, and may thus help to prevent port site metastases.

Abdominal Muscles

[Laparoscopic resection of colorectal malignancy--an oncological risk?].

Oncological risks associated with laparoscopic colorectal surgery in curative intention include inadequate radicality, seeding of tumour cells through unprotected recovery of the surgical specimen, faulty surgical technique, and failure to observe the technical and/or oncological limitations applicable to certain tumour sites. Results of laparoscopic colorectal surgery may be defined by pathohistologic findings (number of removed lymph nodes, count of tumor tears, clearance of margins) and long-term results (port-site metastases, local recurrence rate, number of distnant metastase, 5-year-survival). Current published results and first data from the Multicenter Study Group will be compared with the data of open surgery. Merely a few reports on the number of lymph nodes removed during such operations have been published. First data of the Multicenter Study Group Laparoscopis Colorectal Surgery seem to report comparable data to open surgery. There are no certain data the occurrence rate of portsite metastases as on long-term results, local recurrence rates and the 5-year-survival. So the sense and the quality of laparoscopic colorectal surgery in curative intention can't be judged nowadays. The many potential mistakes and hazards of oncological laparoscopic surgery make it mandatory that such interventions should be done only within the framework of prospective clinical studies covering limited indications.

Colectomy

[Regional cooperation in molecular biology topics].

Research on rare events, such as the occurrence of port-site metastases, can be speeded up by pooling patients from different hospitals. Multidisciplinary approaches, involving surgeons, pathologists and molecular biologists, allow more detailed experimental results to be obtained. Research costs are kept low by using existing infrastructures over a short period of time.

Cost-Benefit Analysis

[Phenotypic analysis in colorectal carcinoma: an international interdisciplinary project].

An European research network grouping surgeons, pathologists, biochemists and molecular biologists is presented. The aim of this network is to define new diagnostic, prognostic and therapeutic markers at protein and RNA levels in colorectal cancer. The methodology is based on specific sample preparation techniques, allowing the isolation of pure epithelial cells, and on differential-display techniques, such as two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and reverse arbitrarily-primed polymerase chain reaction (RAP-PCR).

Biomarkers, Tumor

Hemodynamic effects of intermittent pneumatic compression of the lower limbs during laparoscopic cholecystectomy.

BACKGROUND: The effects of surgical pneumoperitoneum on lower-limb venous hemodynamics have already been studied; however, the effects of intermittent compression boots are not known in such venous-stasis conditions. METHODS: In 12 volunteers and 12 patients, the venous hemodynamic effects of intermittent leg compression were studied under external abdominal pressure or during laparoscopic cholecystectomy, respectively. Femoral venous diameter and velocity were measured. Venous pressure was monitored during the surgical procedures. RESULTS: External abdominal pressure of 50 mm Hg and pneumoperitoneum were found to increase the diameter (17% in the volunteers and 14% in the patients) and decrease peak velocity (49% and 32%, respectively) in the femoral vein. Femoral pressure was increased (106%) during pneumoperitoneum. In both venous-stasis circumstances, intermittent compression of the legs restored venous flow velocity, but had no effect on vessel diameter and pressure. CONCLUSIONS: The lower-limb venous hemodynamic changes were similar during external abdominal pressure or pneumoperitoneum, and the flow velocity decrease was intermittently reversed by pneumatic compression boots.

Adult

[How to reduce the number of negative appendectomies? A prospective two-center study of 120 patients].

A decisional protocol based on clinical findings and laboratory data was assessed prospectively in a consecutive series of 120 patients with suspected appendicitis over a 24-month period at 2 teaching hospitals. Using this protocol the high rate of negative appendectomy (31.5%) during the 2 years prior to the study was reduced to 22% without increasing morbidity or mortality. Ultrasound examination was poorly predictive in unclear cases. Laparoscopy was used to assess diagnosis in persistent symptoms.

Adolescent

[Flexible choledochoscopy: two years experience].

This study is a retrospective review of 258 procedures on the gallbladder and bile ducts (115 without and 143 with flexible choledochoscope). There were 14 bile duct explorations for stone removal without choledochoscopy and 16 with a flexible choledochoscope. Residual stones were found in 2/14 (14.2%) cases without and 1/16 (6.3%) case with choledochoscope. A review of the literature confirms that there are fewer residual bile duct stones following flexible choledochoscopy. There were no complications attributable to the procedure.

Cholelithiasis