Damage control with abdominal vacuum therapy (VAC) to manage perforated diverticulitis with advanced generalized peritonitis--a proof of concept.

PURPOSE: Perforated diverticulitis with advanced generalized peritonitis is a life-threatening condition requiring emergency operation. To reduce the rate of colostomy formation, a new treatment algorithm with damage control operation, lavage, limited closure of perforation, abdominal vacuum-assisted closure (VAC; V.A.C.), and second look to restore intestinal continuity was developed. METHODS: This algorithm allowed for three surgical procedures: primary anastomosis +/- VAC in stable patients (group I), but damage control with lavage, limited resection of the diseased colonic segment, VAC and second-look operation with delayed anastomosis in patients with advanced peritonitis or septic shock (group II), and Hartmann procedure was done for social reasons in stable patients (group III) RESULTS: All 27 consecutive patients (16 women; median age 68 years) requiring emergency laparotomy for perforated diverticulitis (Hinchey III/IV) between October 2006 and September 2008 were prospectively enrolled in the study. No major complications were observed in group I (n = 6). Nine patients in group II (n = 15) had intestinal continuity restored during a second-look operation, of whom one patient developed anastomotic leakage. The median length of stay at intensive care unit was 5 days. Considering an overall mortality rate of 26% (n = 7), the rate of anastomosis in surviving patients was 70%. CONCLUSIONS: Damage control with lavage, limited bowel resection, VAC, and scheduled second-look operation represents a feasible strategy in patients with perforated diverticulitis (Hinchey III and IV) to enhance sepsis control and improve rate of anastomosis.

Dickkopf-3 as a new potential marker for neoangiogenesis in colorectal cancer: expression in cancer tissue and adjacent non-cancerous tissue.

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.

Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival.

PURPOSE: Gallbladder carcinoma is an aggressive type of cancer that is difficult to cure by conventional procedures. There thus is a need to identify novel molecular markers for the assessment of prognosis and as potential therapeutic targets. This retrospective study was designed to investigate the prognostic significance of epithelial cell adhesion molecule (Ep-CAM) overexpression in human gallbladder carcinoma. EXPERIMENTAL DESIGN: Ep-CAM expression was examined immunohistochemically on paraffin-embedded tissue specimens from 99 patients who underwent surgical treatment for gallbladder carcinoma in the period between August 1988 and May 1999. RESULTS: Ep-CAM overexpression was found in 63 (63.6%) of the tumor samples. Kaplan-Meier curves showed that Ep-CAM overexpression was significantly related to decreased overall survival (P < 0.01). Overall survival gradually worsened with increasing Ep-CAM scores. Notably, in the subgroup of pT1 tumors (n = 17), patients without Ep-CAM overexpression had a 5-year overall survival rate of 100% compared with 38% (P = 0.01) for patients with Ep-CAM-overexpressing tumors. By univariate analysis, no correlation was found with conventional clinicopathological parameters. Multivariate analysis, including Ep-CAM expression, pT stage, tumor grade, and resection margin involvement, showed that Ep-CAM overexpression was an independent prognostic marker in gallbladder carcinoma (P = 0.03; relative risk, 1.8). CONCLUSIONS: These results demonstrate for the first time that Ep-CAM overexpression is an independent prognostic marker in gallbladder carcinoma and that its prognostic impact should be validated prospectively. Furthermore, the Ep-CAM antigen represents an attractive target for specific therapies with monoclonal antibodies or specific vaccines in patients with Ep-CAM-overexpressing gallbladder carcinoma.

Gallstone ileus: rare and still controversial.

BACKGROUND: Gallstone ileus is a rare disease and accounts for about 1-3% of mechanic ileus of the small bowel, but for 25% of all small bowel obstructions in patients older than 65 years. Concomitant cardiorespiratory diseases or diabetes are frequent in older patients and responsible for the high mortality rate. The aim of the present study was to evaluate and discuss different surgical approaches and to analyze the clinical outcome. METHODS: Four patients with a mean age of 72 years were treated for gallstone ileus at our hospital in the last 10 years. Patients history, operative strategy and their outcome is elucidated and a review of the recent literature is given. RESULTS: In all patients the operative strategy was a one-stage procedure including enterolithotomy, cholecystectomy and closure of the fistula. The 30-day mortality rate was 25%. CONCLUSION: One-stage procedure prevents from cholangitis, cholecystitis and recurrent ileus caused by further gallstones but bears the risk of enteric or biliary leakage after fistula closure. It should therefore be reserved for patients presenting in good general condition with a low degree of cholecystitis.

DaVinci robotic-assisted laparoscopic bariatric surgery: is it justified in a routine setting?

BACKGROUND: Laparoscopic silicone adjustable gastric banding (SAGB) has gained popularity for the surgical treatment of morbid obesity. The implantable gastric stimulator (IGS) system represents a novel surgical alternative. We aimed to assess the feasibility of robotic-assisted laparoscopic bariatric operations and to critically elucidate the technical and financial advantages and patient outcome. METHODS: Robotic-assisted laparoscopic bariatric procedures were performed on 10 consecutive patients using the daVinci robot system (4 SAGB, 4 IGS, 2 SAGB revisions). 10 conventional laparoscopic-operated patients (4 SAGB, 4 IGS, 2 SAGB revisions) during the learning curve served as controls. Equipment, operative technique and procedural time were evaluated. A cost analysis was calculated. RESULTS: The personnel equipment, numbers of trocars and operation technique were comparable in both groups. The mean operative time was 137 min (range 110-175) and 97 min (60-140) in robotic-assisted and conventional laparoscopy, respectively (P =0.04). Establishment of the pneumoperitoneum and placement of trocars and robotic arms took a mean of 30 min (15-45) in the robotic-assisted group, compared with 5 min in the control group (P <0.001). In 1 patient, intraoperative gastric injury was suspected and led to band removal in the robotic-assisted group. There was no postoperative complication. Average procedural costs were significantly higher in the robotic-assisted group. CONCLUSION: Primary and revisional robotic-assisted bariatric surgery is technically simple, with the benefit of precise instrument handling. However, it is still expensive, the set-up of the system is time-consuming, and a limited variety of instruments are available presently.

Impact of neoadjuvant chemoradiation on anal sphincter function in patients with carcinoma of the midrectum and low rectum.

HYPOTHESIS: Preoperative chemoradiation for patients with stage II and III midrectal and low rectal cancer may improve survival and decrease local recurrence rate. We evaluated the long-term impact of neoadjuvant chemoradiation on anal sphincter function. DESIGN: Prospective analysis. SETTING: Tertiary referral center. PATIENTS: From March 1, 1996, to January 31, 2002, 50 patients with midrectal and low rectal cancer who underwent total mesorectal excision were prospectively enrolled. INTERVENTIONS: Patients received either surgical therapy alone (group 1, n = 22) or preoperative, combined chemoradiation (group 2, n = 28). Group 2 was divided into patients with midrectal (group 2A, n = 14) and low rectal (group 2B, n = 14) cancer. Anorectal manometry was performed preoperatively and a median of 384 days postoperatively. MAIN OUTCOME MEASURES: Anal resting pressure, squeeze pressure, anal sphincter vector volumes, length of the high-pressure zone, sensory threshold of the pouch, and rectal capacity. RESULTS: Preoperative manometric values were comparable between the groups. No statistically significant manometric differences occurred in group 1 postoperatively. Mean resting pressure (preoperative and postoperative, respectively: 89 +/- 35 mm Hg, 53 +/- 17 mm Hg), resting vector volume (605 +/- 324 cm( 3), 142 +/- 88 cm(3)), and maximal tolerable volume (144 +/- 29 mL, 82 +/- 44 mL) decreased significantly in chemoradiated patients postoperatively (P<.05). Manometric values of group 2B patients remained stable postoperatively, while mean resting pressure (73 +/- 22 mm Hg vs 52 +/- 14 mm Hg) and resting vector volume (631 +/- 288 cm(3) vs 145 +/- 78 cm(3)) decreased significantly in group 2A patients (P<.001). CONCLUSIONS: Total mesorectal excision does not influence anal sphincter function during long-term follow-up. Neoadjuvant chemoradiation results in disordered anal sphincter function in patients with midrectal cancer. Low and rectoanal anastomosis seems to obtain better anal sphincter function than higher anastomosis in chemoradiated patients.

14-3-3 sigma and p53 expression in gastric cancer and its clinical applications.

14-3-3 sigma (σ) induces G2 arrest enabling the repair of damaged DNA. The function of 14-3-3 σ is frequently lost in tumor cells, indicating a potential tumor suppressor function. The purpose of this study was to evaluate the prognostic value of 14-3-3 σ expression in human gastric cancer. 14-3-3 σ expression was analyzed by immunohistochemistry in 157 tumor samples of patients, who underwent resection for gastric cancer. Since 14-3-3 σ is involved in the p53 network, p53 expression was detected in parallel and correlated with 14-3-3 σ. 14-3-3 σ was found to be overexpressed in 75 (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3 σ overexpression was statistically significantly associated with pT-stage (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline significance with Lauren classification (p=0.057). Univariate survival calculations revealed a coexistent 14-3-3 σ and p53 overexpression as a significant predictor of disease-free survival. Multivariate analysis did not unfold 14-3-3 as an independent prognostic factor for disease-free survival and overall survival. Concomitant 14-3-3 σ and p53 overexpression in tumor cells of patients with gastric cancer identifies a population of patients with relatively unfavorable prognosis.

Immunohistochemically detectable dickkopf-3 expression in tumor vessels predicts survival in gastric cancer.

Dickkopf-3 (Dkk-3) may act as a tumor suppressor as it is downregulated in various types of cancer. Moreover, a putative role in tumor neovascularization is discussed. Here, we investigated the expression of Dkk-3 protein in gastric cancer and its potential value as a prognostic marker. Dkk-3 expression was analyzed by immunohistochemistry in 136 tumor samples and was correlated with microvessel density (MVD), tumor stage, and grading as well as the clinical outcome of the patients. Dkk-3 expression was detected in endothelial cells of the tumor vessels in 129/136 (94.9%) and in tumor cells in 85/136 (62.5%) samples. MVD was high and low in 57 (42.9%) and 76 (57.1%) specimens respectively. In tumor cells, overexpression of Dkk-3 was found in 41 (30.1%) of all cases and was correlated significantly to pT-stage (p < 0.05) and UICC stage (p < 0.05). Survival analysis regarding Dkk-3 expression in tumor endothelial cells showed that Dkk-3 is an independent predictor of disease-free survival (p < 0.05). Dkk-3 expression in tumor vessels of patients with gastric cancer identifies a population of patients with relatively favorable prognosis.

Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers.

Prostate-specific membrane antigen (PSMA), a type II transmembrane metallo-peptidase highly overexpressed in prostate cancer cells, has been studied as a targeting molecule in prostate cancer. Recently, PSMA has also been found to be expressed in the neovasculature of multiple nonprostatic solid tumors. Because of its unique expression pattern limited to tumor-associated endothelial cells, PSMA may also be an interesting molecule for vascular targeting. In this study, PSMA expression was determined by immunohistochemistry in 119 cases of primary gastric adenocarcinoma, 130 cases of primary colorectal adenocarcinoma, and 24 metastasis of colorectal adenocarcinoma. Expression data were correlated with clinicopathologic information. PSMA expression was detected in tumor-associated neovasculature of 79 (66%) of 119 gastric and 110 (85%) of 130 colorectal carcinomas. Furthermore, the neovasculatures of 16 (84%) of 19 liver and 4 (80%) of 5 nodal metastases from colorectal carcinomas were prostate-specific membrane antigen positive. There was a trend for high-grade tumors to higher PSMA expression (Spearman r = 0.18, P = .046) in colorectal cancers. No association between PSMA expression and overall- or disease-free survival was observed in gastric or colorectal cancers. This study provides the first in-depth look at PSMA expression in gastric and colorectal cancer. Because of its highly tumor-restricted expression and its accessibility to targeted therapy, PSMA represents a promising therapeutic and diagnostic target in colorectal and gastric cancer.

SFRP2 methylation in fecal DNA--a marker for colorectal polyps.

INTRODUCTION: DNA methylation of secreted frizzled-related proteins (SFRPs) can be detected in colorectal cancer (CRC) tissue, in tissue of adenomas, and in aberrant crypt foci, whereas in normal colorectal mucosa tissue, SFRP genes are unmethylated. Recently, our study group was able to demonstrate SFRP2 methylation as the most sensitive single DNA-based marker in stool for identification of CRC. The purpose of this study was to clarify whether SFRP2 methylation in fecal DNA can be found in stool of individuals with hyperplastic and adenomatous colorectal polyps. MATERIALS AND METHODS: Patients who were diagnosed with colorectal polyps or showed negative colonoscopy were included in this study. DNA from stool samples was isolated. SFRP2 methylation was assessed by means of MethyLight. RESULTS: Stool samples from 68 individuals were checked for DNA content; 23% of the samples (6 of 26) from healthy controls, 46% of the samples (6 of 13) from patients with hyperplastic polyps, and 45% of the samples (13 of 29) from patients with adenomas were positive for human DNA. SFRP2 methylation in stool samples was found in none of the healthy controls, in 33% (2 of 6) patients with hyperplastic polyps, and in 46% (6 of 13) patients with adenomas. Statistical analysis revealed that the frequency of SFRP2 methylation increased significantly (P=0.028) from healthy controls to patients with hyperplastic polyps and to patients with adenomas. CONCLUSIONS: In the current study, we report for the first time that SFRP2 methylation in fecal DNA increases significantly from healthy controls to patients with hyperplastic polyps and to patients with adenomas. SFRP2 methylation may serve as a marker for molecular stool-based adenoma and CRC screening.

Assessment of risk-independent follow-up to detect asymptomatic recurrence after curative resection of colorectal cancer.

BACKGROUND AND AIMS: Colorectal cancer is one of the leading causes of cancer death. We analyzed the value of standardized, risk-independent postoperative surveillance. MATERIALS AND METHODS: Between 1995 and 2001, 564 patients with colorectal cancer underwent standardized oncologic resection. One hundred thirty-four were unable to take part in the surveillance program, while 430 patients were grouped as follows: group I (n=272, risk-independent follow-up), group II (n=113, follow-up at other departments), and group III (n=45, no follow-up). RESULTS: The 5-year cancer-specific survival rate for UICC III and IV was significantly higher in group I (87%) as compared to group II (35%). In group I, the 5-year disease-free survival rate was 70%. Cancer recurrence occurred at mean 17 (+/-12) months after colorectal resection and yielded a 5-year survival rate of 63%. Reresection was performed in 17 (35%) patients, of whom ten remained disease-free (5-year survival rate, 91%). The money spent for one patient's 5-year follow-up was 1665. CONCLUSIONS: A standardized, risk-independent follow-up program allows early diagnosis of asymptomatic recurrence of colorectal cancer. Reresection improves the 5-year survival rate in this setting.

Selection of patients with gastroesophageal reflux disease for antireflux surgery based on esophageal manometry.

Gastroesophageal reflux disease (GERD) is caused by a mechanically defective lower esophageal sphincter (LES) and may be worsened by impaired esophageal peristalsis. The aim of this study was to evaluate the efficacy of medical treatment depending on the function of the LES and esophageal peristalsis. We studied 128 GERD patients with mild esophagitis. Group 1 (N = 26) consisted of patients with a normal LES and normal esophageal peristalsis. Group 2 (N = 63) comprised patients with a defective LES but normal peristalsis. Patients of group 3 (N = 39) had a defective LES as well as impaired esophageal peristalsis. The patients were continuously treated with omeprazole. Clinical evaluation and endoscopy were repeated after 3, 6, and 12 months. Recurrence of GERD was diagnosed if there was relapse of heartburn and/or esophagitis. The recurrence rate was 7.7% in group 1, 38.1% in group 2 (P < 0.05) and 79.5% in group 3 (P < 0.05). In conclusion, in GERD patients with a mechanically defective LES, especially in those with deteriorated esophageal peristalsis, antireflux surgery should be considered since medical therapy reveals a high recurrence rate.