Predictive factors for postoperative constipation and continence after stapled transanal rectal resection.

BACKGROUND: Although stapled transanal rectal resection (STARR) has become an important surgical option in the treatment of obstructive defaecation syndrome, objective data about parameters that predict its success or failure are not yet available. METHODS: Medical history, clinical and radiomorphological data were obtained prospectively from a multi-institutional STARR registry. Predictive factors for postoperative constipation (Cleveland Clinic Constipation Score, CCS) and incontinence (Cleveland Clinic Incontinence Score, CCIS) were identified using univariable and multivariable analysis. RESULTS: Data were obtained for 181 of 201 patients in the STARR registry, with completed median follow-up of 19·4 (range 12-41) months. Although the CCS decreased significantly overall (from mean(s.d.) 16·3(4·9) to 6·7(4·1); P < 0·001), 31 patients (17·1 per cent) complained about persisting constipation. CCIS levels remained unchanged overall, but 16 patients (8·8 per cent) had new-onset faecal incontinence. Multivariable analysis revealed that rectocele (ß = -0·302, P < 0·001) and intussusception (ß = -0·392, P < 0·001) were independent predictors of low CCS levels, and intussusception (ß = -0·216, P = 0·001) and enterocele (ß = -0·171, P = 0·012) were independent predictors of low CCIS levels. In contrast, small rectal diameter (ß = -0·293, P < 0·001), low squeeze pressure (ß = -0·188, P = 0·005) and increased pelvic floor descent at rest (ß = 0·264, P < 0·001) predicted high CCIS levels. CONCLUSION: Factors for a favourable outcome after STARR included rectocele, intussusception and enterocele, whereas small rectal diameter, low sphincter pressure and increased pelvic floor descent were unfavourable. These findings should be integrated into the therapy algorithm for STARR.

Stapled transanal rectal resection and sacral nerve stimulation - impact on faecal incontinence and quality of life.

AIM: The aim of the study was to assess the impact of stapled transanal rectal resection (STARR) on pre-existing faecal incontinence and quality of life in patients suffering from obstructive defaecation syndrome (ODS) and to evaluate the efficiency of sequential sacral nerve stimulation (SNS) for improvement of persistent incontinence after STARR. METHOD: Thirty-one patients with ODS and major faecal incontinence prior to STARR were prospectively enrolled. The outcome was measured using the Cleveland Clinic Constipation and Incontinence score (CCS, CCIS), Faecal Incontinence Qualities-of-Life Index (FIQL), Patient Assessment of Constipation Quality-of-Life (PAC-QOL) and EuroQol visual analogue scale (EQ-VAS). RESULTS: The overall levels of constipation (CCS from 13.1 ± 3.8 to 6.2 ± 5.4; P < 0.001) and incontinence (CCIS from 12.6 ± 3.2 to 9.4 ± 5.1; P = 0.005) were significantly improved after STARR; concordantly, the global and specific quality of life were significantly improved. Following postoperative constipation and incontinence, three different groups of patients were differentially referred to SNS. In group I (n = 16, 52%), both constipation (CCS from 12.6 ± 4.0 to 3.6 ± 1.9; P < 0.001) and incontinence (CCSI from 12.43 ± 3.2 to 5.1 ± 1.9; P < 0.001) were improved. In group II (n = 8, 25%), only constipation was improved (CCS from 12.3 ± 2.3 to 3.3 ± 2.2; P < 0.001), while incontinence persisted (CCIS from 12.8 ± 2.9 to 13.1 ± 3.1; P > 0.05). In group III (n = 7, 23%) there was no improvement at all. Sacral nerve stimulation was successfully carried out in six (85%) of seven patients in group II (post-SNS CCSI 6.1 ± 1.7; P = 0.01) but failed in five of five patients in group III. CONCLUSION: Stapled transanal rectal resection improves quality of life in ODS patients with both severe constipation and faecal incontinence. Sacral nerve stimulation may efficiently improve persisting incontinence after STARR in selected patients.

Enterocele is not a contraindication to stapled transanal surgery for outlet obstruction: an analysis of 170 patients.

AIM: Enterocele is common among patients suffering from obstructive defecation syndrome (ODS), but it is often considered a contraindication for stapled transanal surgery. The functional results and complication rates were compared in patients with or without enterocele who were treated with stapled transanal rectal resection (STARR) for ODS. METHOD: Patients presenting with ODS were evaluated using standardized clinical and radiological investigations. A total of 170 patients were treated with either PPH01-STARR or Contour Transtar® and were followed up for a median of 18 months. RESULTS: On preoperative defecography, 55 (32%) of 170 patients were found to have an enterocele. The preoperative Cleveland Clinic Constipation Scores (CCCS) in patients with and without enterocele were (mean ± standard deviation) 15.9 ± 5.4 and 15.4 ± 5.2, respectively. At 18 months postoperatively the CCCS were 8.5 ± 2.7 and 8.1 ± 2.6 (P < 0.001), respectively, in patients with and without enterocele. Morbidity was 7.3% (n = 4) in patients with enterocele (anal pain, n = 1; minor bleeding, n = 2; and acute urinary retention, n = 1) and 7.0% (n = 8) in patients without enterocele (anal pain, n = 3; minor bleeding, n = 3; acute urinary retention, n = 1; and staple line dehiscence, n = 1). There were no cases of pelvic sepsis, small bowel injury or postoperative ileus. No patient needed surgical re-operation. CONCLUSION: There was no difference in functional outcome and postoperative complications in patients with and without enterocele undergoing STARR for ODS.

Quality of life after transperineal rectosigmoidectomy.

BACKGROUND: : This study evaluated continence, constipation and quality of life before and after perineal rectosigmoidectomy for full-thickness rectal prolapse. METHODS: : Consecutive patients with full-thickness rectal prolapse undergoing perineal rectosigmoid- ectomy (Altemeier's procedure) between May 2004 and June 2008 were studied. A standardized questionnaire, including the Cleveland Clinic Constipation Score (CCCS), Cleveland Clinic Incontinence Score (CCIS) and quality of life scores (EuroQol-Five Dimensions, EuroQol-Visual Analogue Scale and Patient Assessment of Constipation-Quality of Life (PAC-QOL)), was administered before and after operation. RESULTS: : Thirty-eight patients (32 women) of mean(s.d.) age 75(13) years underwent rectosigmoid- ectomy. Seven patients developed postoperative complications and one died. There was one recurrence 5 months after surgery. Twenty-nine patients completed the follow-up questionnaire and were reviewed after a median of 24 (range 6-48) months. Constipation and incontinence were significantly improved after surgery (mean CCCS from 10.21 to 3.58 and CCIS from 14.17 to 11.42; P < 0.001). Quality of life, in terms of mobility, usual activities, pain/discomfort and anxiety/depression, were significantly better at follow-up (P < 0.001), as was subjective health status (P < 0.001). The PAC-QOL score improved significantly in all dimensions (P < 0.001). CONCLUSION: : Transperineal rectosigmoidectomy improves general and constipation-related quality of life with good functional results.

Comparative study of Contour Transtar and STARR procedure for the treatment of obstructed defecation syndrome (ODS)--feasibility, morbidity and early functional results.

AIM: Stapled transanal rectal resection (STARR) is a promising new treatment for obstructed defecation syndrome (ODS). It may be performed using either a double-stapling technique (PPH-STARR) or with the new Contour Transtar (CT) device. The aim of this study was to evaluate the two techniques with respect to morbidity and functional outcomes. METHOD: Patients presenting with ODS were evaluated using standardized clinical and radiological investigations and prospectively entered into a database. A total of 150 Patients were treated with either PPH-STARR (n = 68) or CT (n = 82) and further evaluated at 12 month postoperatively. RESULTS: The mean size of the resected specimen was 27 cm(2) (SD +/-4.86 cm(2)) in the PPH-STARR group and 46 cm(2) (SD +/-10.6 cm(2)) in the CT group [P < 0.001]. Morbidity was 7.3% (n = 5) in the PPH-STARR group and 7.5% (n = 6) in the CT group. The most common complication was minor postoperative bleeding in both groups (PPH-STARR: n = 2, 2.9%; CT: n = 2, 2.4%) Overall there were no septic complications and no surgical re-interventions. There was a tendency for more postoperative pain following CT (n = 3, 3.6%) as compared with PPH-STARR (n = 1, 1.4%). Constipation Scores (CCS) were 15.50 +/- 5.71 in the PPH-STARR group and 15.70 +/- 5.84 in the CT group preoperatively and decreased significantly to 8.25 (SD +/-1.45) and 8.01 (SD +/-2.31) 12-months after surgery. Values did not differ significantly between the two groups. CONCLUSIONS: Contour Transtar is as safe and effective as PPH-STARR and provides a true circumferential resection of rectal intussusception. This may benefit selected patients and result in improved long-term durability of the technique.

Bcl-XL protects pancreatic adenocarcinoma cells against CD95- and TRAIL-receptor-mediated apoptosis.

In this study we sought to clarify the role of the proapoptotic potential of mitochondria in the death pathway emanating from the TRAIL (APO-2L) and CD95 receptors in pancreatic carcinoma cells. We focused on the role of the Bcl-2 family member Bcl-XL, using three pancreatic carcinoma cell lines as a model system, two of which have high (Panc-1, PancTuI) and one has low (Colo357) Bcl-XL expression. In these cell lines, the expression of Bcl-XL correlated with sensitivity to apoptosis induced by TRAIL or anti-CD95. Flow cytometric analysis revealed cell surface expression of TRAIL-R1 and TRAIL-R2 on PancTuI and Colo357, and TRAIL-R2 on Panc-1 cells. In Colo357 cells retrovirally transduced with Bcl-XL, caspase-8 activation in response to treatment with TRAIL or anti-CD95 antibody was not different from parental cells and EGFP-transfected controls, however, apoptosis was completely suppressed as measured by the mitochondrial transmembrane potential deltapsim, caspase-3 activity (PARP cleavage) and DNA-fragmentation. Inhibition of Bcl-XL function by overexpression of Bax or administration of antisense oligonucleotides against Bcl-XL mRNA resulted in sensitization of Panc-1 cells to TRAIL and PancTuI cells to anti-CD95 antibody-induced cell death. The results show that Bcl-XL can protect pancreatic cancer cells from CD95- and TRAIL-mediated apoptosis. Thus, in these epithelial tumour cells the mitochondrially mediated 'type II' pathway of apoptosis induction is not only operative regarding the CD95 system but also regarding the TRAIL system.

Transduction of human pancreatic tumor cells with vesicular stomatitis virus G-pseudotyped retroviral vectors containing a herpes simplex virus thymidine kinase mutant gene enhances bystander effects and sensitivity to ganciclovir.

We examined the suitability of Moloney murine leukemia virus (MLV) 4070A-, cat endogenous virus (CEV) RD114-, or vesicular stomatitis virus G (VSV-G)-pseudotyped retroviruses containing the humanized enhanced green fluorescent protein (hEGFP) or one of two herpes simplex virus thymidine kinase (HSV-TK) genes to transduce and provide gene expression in human pancreatic tumor cells. Fluorescence-activated cell sorter analysis demonstrated that VSV-G-pseudotyped hEGFP vector infected a greater percentage of cells and generated more robust gene expression than MLV 4070A- or CEV RD114-pseudotyped vectors. Dot blot and Southern blot analysis of genomic DNA revealed up to 10-fold more gene copies in G418-selected VSV-G hEGFP vector-transduced cells compared with genomic DNA from cells transduced with MLV 4070A or CEV RD114 pseudotypes. Cells transduced with VSV-G pseudotypes of HSV-TK(WT) or the HSV-TK30 vectors were 5- to 10-fold more sensitive to ganciclovir (GCV) than other pseudotype-transduced cells. A 40- to 61-fold difference in sensitivity to GCV was observed between cells transduced with VSV-G HSV-TK30 vector and cells transduced with MLV 4070A HSV-TK(WT) vector in vitro. A 13-fold reduction in tumor volume was observed in severe combined immunodeficient mice inoculated with PancTuITK30 cells compared with mice inoculated with PancTuITK(WT) cells during GCV treatment. We conclude that the choice of glycoprotein envelope and the potency of a particular suicide gene were therapeutically additive and increased the number of HSV-TK-positive cells and sensitivity toward GCV in human pancreatic tumors cells for prodrug gene therapy.

Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel perforation in an otherwise healthy individual: report of a case.

BACKGROUND: Abdominal gas gangrene caused by clostridia species is rare and usually associated with organ perforation, immune suppression, or advanced malignoma. CASE REPORT: A 61-year-old man was admitted with severe back pain 1 day after uncomplicated colonoscopic polypectomy. With the exception of preexisting minor depression, the patient had been previously in excellent health. The computed tomography scan showed retroperitoneal emphysema in the left psoas muscle. During exploratory laparotomy, a spreading retroperitoneal phlegmon with pneumoretroperitoneum and a secondary peritonitis were found. A macroscopic perforation of the gut, particularly at the polypectomy sites was excluded. After the operation, the patient evolved in a septic shock condition and had pulmonary failure. Before hyperbaric oxygen therapy could be employed, the patient died. The autopsy showed a massive gas gangrene of the retroperitoneum caused by Clostridium perfringens, but no macroscopic bowel perforation was detected. RESULTS: This is the first report of a case of gas gangrene after uncomplicated polypectomy without macroscopic perforation in an otherwise healthy individual. A microperforation due to mucosal defect after polypectomy was most likely the entry point for the bacteria. CONCLUSION: We conclude that clostridial myonecrosis should be considered in unclear abdominal infections, even if the patient's history is not typical as in the present case.

Apoptosis by gemcitabine in non-small cell lung cancer cell line KNS62 is induced downstream of caspase 8 and is profoundly blocked by Bcl-xL over-expression.

BACKGROUND: This study assesses the chemotherapeutic drug gemcitabine in the human non-small cell lung cancer (NSCLC) cell line KNS62 in relation to the CD95-induced apoptotic pathway, and the role of the anti-apoptotic protein Bcl-xL in vitro and in vivo. MATERIALS AND METHODS: Apoptosis was determined by JAM assay and DAPI staining analysis. Activation of key apoptotic proteins, including caspases 3, 8 and 9 and BID, as well as cytochrome c release and mitochondrial transmembrane potential (MTP), were measured. The impact of the caspase inhibitor zVAD on gemcitabine-induced apoptosis was quantified. The in vitro results were verified in vivo in an orthotopic murine xenotransplantation model. RESULTS: Gemcitabine treatment, as well as stimulation of CD95, resulted in cleavage of effector caspase 3 as well as its substrate PARP and caspase 9, followed by DNA fragmentation. Cleavage of caspase 8 was demonstrated after CD95 activation but not after the application of gemcitabine. In KNS62-Bcl-xL clones, release of cytochrome c and loss of mitochondrial transmembrane potential were suppressed. Consequently, apoptosis after gemcitabine therapy, as well as CD95-induced apoptosis, were significantly inhibited. Caspase inhibitor zVAD only partly reversed gemcitabine-induced DNA fragmentation. In vivo, there was a significant reduction in tumour volume under gemcitabine therapy. Bcl-xL over-expressing tumours were completely resistant to gemcitabine therapy. CONCLUSIONS: In NSCLC cell line KNS62 gemcitabine activated the mitochondrial apoptotic pathway downstream of mitochondria without activation of initiator caspases. Bcl-xL over-expression induced significant resistance to gemcitabine. In vivo, the anti-apoptotic effect of Bcl-xL was more pronounced than in vitro. Gemcitabine also induced caspase-independent DNA fragmentation in KNS62 cells.