Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort.

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.

Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO).

INTRODUCTION: Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions. METHODS: PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses. DISCUSSION: Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies.

Non-mucinous adenocarcinomas and squamous cell carcinomas of the anal region masquerading as abscess or fistula: a retrospective analysis and systematic review of literature.

PURPOSE: Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in advanced tumour stages at first diagnosis. Due to the case rarity, treatment guidelines for cancers of anorectal region masquerading as abscess or fistula are missing. METHODS: We analysed all patients presenting with an abscess or fistula of the anal region in our department between January 2004 and August 2020. The malignancies were included to our study to acquire data on clinical presentation, treatment and outcome. Furthermore, a systematic review to present adenocarcinomas and squamous cell carcinomas associated to an abscess or fistula was performed. RESULTS: 0.5% of the patients treated for an abscess or fistula of the anal region met the selection criteria. Mean time from the onset of symptoms to diagnosis of malignancy was 100 days. Histology revealed adenocarcinoma and squamous cell carcinoma each in two patients. All patients had locally advanced tumours without distant metastases, in two cases with regional lymph-node metastases. Neoadjuvant chemoradiation was applied in two patients. All patients underwent abdomino-perineal resection of the rectum. The overall outcome reveals a recurrence-free survival of 4.5 and 3 years for two patients. Further two patients died within 5 months after the primary resection. CONCLUSION: Advanced carcinomas of the anorectal region may masquerade as abscess or fistula, cause diagnostic problems and delay oncologic treatment. However, even in these very advanced situations, surgical therapy with curative intent should be attempted.

Vaginal cysts: An important differential diagnosis in the anterior compartment.

INTRODUCTION: Benign anterior-vaginal-wall cysts (0.5-1% prevalence) often mimic other structures (e.g. cystoceles). No algorithm for their diagnosis, treatment, recurrence or complication prediction can be derived from existing data. Careful preoperative diagnosis can minimize intraoperative surprises and complications due to differences in cyst origin. METHODS: This retrospective study was performed with data from consecutive patients with anterior vaginal cysts who underwent surgery at the Pelvic Floor Centre, University Women's Hospital of Jena, within a period of 7 years. Data on patient age, symptoms, history of previous surgery, lesion characteristics, preoperative imaging findings, surgeries, postoperative stays, complications and histological and microbiological findings were collected. RESULTS: Out of 797 consecutive anterior vaginal prolapse repairs 19 (2.4%) anterior vaginal cystic lesions were found, mean age 47 [standard deviation (SD) 14, range 22-72] years. Symptoms reported were pressure (58%), voiding dysfunction (26%), dyspareunia (5%) and inflammation signs (37%); 26% of cases were asymptomatic. Two patients had received prolapse pessary treatment before. Two patients had history of previous vaginal surgery. Five cases were diagnosed preoperatively by ultrasound. Cysts were located on the medial anterior vaginal wall (42%), suburethral (42%) and the vaginal apex (16%). The mean lesion size was 2.6 (SD 0.9) cm. Eleven percent of cases showed microbiological positivity. Most (89%) vaginal cysts were excised; 11% were fenestrated, biopsied and drained. Twenty-six percent of patients underwent outpatient procedures; for inpatient procedures, the median stay was 2.7 days. Postoperative hemorrhage with no transfusion requirement occurred in one patient. All lesions were benign. CONCLUSIONS: Anterior-compartment vaginal cysts can be found incidentally during pelvic organ prolapse assessment and surgery, as they can mimic anterior-vaginal-wall prolapse. In this cohort, all excised lesions were benign.

Risk factors for esophageal cancer in a high-incidence area of Malawi.

PURPOSE: To explore associations of nutritional, infectious, and lifestyle factors with esophageal cancer (EC) occurrence in a high-risk area of Malawi. METHODS: This case-control study was performed with 227 patients undergoing endoscopy for dysphagia or other upper gastrointestinal complaints. Data on clinicopathological characteristics and risk factors were collected using a questionnaire developed for this study specifically. Ninety-eight blood samples were collected and the prevalence of antibodies against human immunodeficiency virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and Helicobacter pylori were determined serologically. RESULTS: The tumor and control groups comprised 157 (69.2%) and 70 (31.8%) patients, respectively. Patients with tumors were significantly older than controls (55.5 vs. 43.5 years, p < 0.001). The male/female ratio did not differ between groups (59% and 54% male, respectively; p = 0.469). EC was associated with smoking (p < 0.001), and alcohol consumption (p = 0.020), but 43% of patients with tumors did not smoke or drink. EC was associated with the consumption of hot food and tea (p = 0.003) and smoked fish (p = 0.011). EC was not associated with any serologically investigated infectious agents. In an age adjusted binary logistic regression analysis of all nutritive factors, only locally made alcohol was significant [odds ratio (OR), 9.252; 95% confidence interval (CI), 1.455-58.822; p = 0.018]. CONCLUSIONS: Apart from alcohol consumption and smoking, the consumption of hot food or tea and smoked fish are associated with EC. Locally distilled alcohol consumption increases the EC risk in Malawi.

Monitoring of the Progression of the Perioperative Serum Lactate Concentration Improves the Accuracy of the Prediction of Acute Mesenteric Ischemia Development After Cardiovascular Surgery.

OBJECTIVES: To examine the sensitivity and specificity of perioperative lactate gradients for the prediction of subsequent acute mesenteric ischemia development in patients undergoing cardiovascular surgery. DESIGN: Retrospective, single-center, case-control study. SETTING: University hospital. PARTICIPANTS: The study comprised 108 (1.15%) patients with acute mesenteric ischemia who were selected from 9,385 patients who underwent cardiovascular surgery and were matched to 324 control patients by age and surgery type. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Univariate and logistic regression analyses were used to examine intraoperative and early postoperative lactate levels in patients with and without mesenteric ischemia after cardiac surgery. Late intraoperative lactate concentrations were significantly greater in patients who subsequently developed mesenteric ischemia (p < 0.001). Patients with lactate levels >3 mmol/L had a four-fold increased risk of mesenteric ischemia development (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.4-7.5; area under the curve [AUC] 0.597; p < 0.002). Patients whose lactate levels remained >3 mmol/L on the first postoperative day had a nearly eight-fold increased risk (OR 7.8, 95% CI 4.6-13.3; AUC 0.68; p < 0.001), indicating that mesenteric ischemia developed at an early stage in almost every second patient (p < 0.001). For patients with normal or less elevated lactate levels, similar results were obtained for a >200% increase between the intraoperative and early postoperative periods (OR 4.1, 95% CI 2.4-6.8; AUC 0.62; p < 0.001). CONCLUSION: Late intraoperative and early postoperative lactate levels >3 mmol/L and increases >200%, even when remaining within the normal range, should raise the suspicion of subsequent mesenteric ischemia development.

The role of computed tomography in the diagnostic pathway of acute mesenteric ischemia: a nested case-control study.

BACKGROUND: Computed tomography (CT) can be used as the primary screening modality for the evaluation of patients suspected of having acute mesenteric ischemia known to show high sensitivity and specificity rates. PURPOSE: To prove the value of CT in patients with pathological abdominal findings following cardiac surgery. MATERIAL AND METHODS: In a retrospective case-control study, 12 different CT scan parameters of patients with or without mesenteric ischemia following cardiac surgery were compared using univariate and logistic regression analyses. RESULTS: Of 14,176 patients, 133 (0.9%) received an abdominal CT scan during postoperative care due to pathological abdominal findings. Sixty-eight patients were diagnosed with acute mesenteric ischemia. In-hospital mortality was 73.5% for this group. CT parameters with the highest specificity for indicating colonic ischemia were intestinal (99%) or porto-venous (96%) pneumatosis, abnormal contrast medium enhancement (89%), and occlusion of the proximal inferior mesenteric artery (81%). All of those parameters showed low sensitivity levels in the range of 15%-23%. A statistically significant association between acute mesenteric ischemia and CT appearance was obtained for contrast medium enhancement (odds ratio [OR] 12.2, 95% confidence interval [CI] 1.5-99.2) and intestinal pneumatosis (OR 21.0, 95% CI 2.7-165.2) only. CONCLUSION: The typical CT criteria indicating mesenteric ischemia lose their accuracy in patients under critical clinical conditions. As CT remains the first-line diagnostic imaging modality for abnormal abdominal findings following cardiac surgery, negative signs should not prevent early laparotomy if clinical suspicion remains high.

LAVH superior to TVH when concomitant salpingo-oophorectomy is intended in prolapse hysterectomy: a comparative cohort study.

PURPOSE: This comparative cohort study evaluated the influence of surgical route for prolapse hysterectomy (vaginal or laparoscopically assisted) on the achievement of intended elective salpingo-oophorectomy, which was a procedural goal planned with the patient before primary vaginal native-tissue prolapse surgery. METHODS: Consecutive patients who underwent total vaginal hysterectomy (TVH; n = 163) or laparoscopically assisted vaginal hysterectomy (LAVH; n = 144) and vaginal native-tissue repair for pelvic organ prolapse at Jena University Hospital were enrolled. RESULTS: Peri- and postoperative parameters, including Clavien-Dindo (CD) classification of surgical complications, were compared between groups using Student's t test, Fisher's exact test, and multivariable regression. Patient characteristics were similar, except that grade IV prolapse was more common in the LAVH group (p < 0.001). The following parameters differed between the TVH and LAVH groups: concomitant salpingectomy (1.2% vs. 34%) and salpingo-oophorectomy (45% vs. 66%), non-performance of intended salpingo-oophorectomy (36% vs. 0% OR 0.006, 95% CI < 0.001-0.083), adhesiolysis (0% vs. 44%), CD II-III complications (51% vs. 14.6% p < 0.001), operating time (153 ± 61 vs. 142 ± 27 min), and postoperative in-patient days (9.02 ± 4.9 vs. 4.99 ± 0.96; all p < 0.001). CONCLUSIONS: LAVH enabled the safe performance of planned concomitant salpingo-oophorectomy in all cases. To achieve the procedural goal in such cases, laparoscopic assistance in prolapse hysterectomy should be considered.

Detection of HPV16 in Esophageal Cancer in a High-Incidence Region of Malawi.

This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis. HPV DNA was detected using multiplex Quantitative PCR (qPCR) and in situ hybridization (ISH). p16INK4a staining served as a surrogate marker for HPV oncogene activity. Cell proliferation was determined by Ki-67 staining. Human immunodeficiency virus (HIV) status was evaluated by serology. Data on the consumption of alcohol and tobacco, and history of tuberculosis (TBC), oral thrush, and Herpes zoster, were obtained by questionnaire. Forty patients displayed ESCC, three displayed dysplastic epithelium, and 12 displayed normal epithelium. HPV16 was detected in six ESCC specimens and in one dysplastic lesion. Among HPV-positive patients, viral load varied from 0.001 to 2.5 copies per tumor cell. HPV DNA presence could not be confirmed by ISH. p16INK4a positivity correlated with the presence of HPV DNA (p = 0.03). Of particular note is that the Ki-67 proliferation index, in areas with diffuse nuclear or cytoplasmatic p16INK4a staining ≥50%, was significantly higher in HPV-positive tumors compared to the corresponding p16INK4a stained areas of HPV-negative tumors (p = 0.004). HPV infection in ESCC was not associated with the consumption of tobacco or alcohol, but there were significantly more patients drinking locally brewed alcohol among HPV-positive tumor patients compared to non-tumor patients (p = 0.02) and compared to HPV-negative tumor patients (p = 0.047). There was no association between HIV infection, history of TBC, Herpes zoster, oral thrush, or HPV infection, in ESCC patients. Our indirect evidence for viral oncogene activity is restricted to single tumor cell areas, indicative of the role of HPV16 in the development of ESCC. The inhomogeneous presence of the virus within the tumor is reminiscent of the "hit and run" mechanism discussed for ß-HPV types, such as HPV38.

Task-shifting of orthopaedic surgery to non-physician clinicians in Malawi: effective and safe?

There is a shortage of orthopaedic surgeons in Malawi. Orthopaedic clinical officers (OCOs) treat trauma patients and occasionally perform major orthopaedic surgery. No studies have assessed the efficacy and safety of their work. The aim of this study was to evaluate their contribution to major orthopaedic surgery at Zomba Central Hospital. Data about orthopaedic procedures during 2006-2010 were collected from theatre books. We selected major amputations and open reductions and plating for outcome analysis and collected details from files. We compared patients operated by OCOs alone ('OCOs alone' group) and by surgeons or OCOs assisted by surgeons ('Surgeon present' group). OCOs performed 463/1010 major (45.8%) and 1600/1765 minor operations (90.7%) alone. There was no difference in perioperative outcome between both groups. OCOs carry out a large proportion of orthopaedic procedures with good clinical results. Shifting of clinical tasks including major orthopaedic surgery can be safe. Further prospective studies are recommended.

Bowel Ischemia in ICU Patients: Diagnostic Value of I-FABP Depends on the Interval to the Triggering Event.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) has been shown to be of high diagnostic value in patients with acute mesenteric ischemia. Whether these results can be reproduced in critically ill patients on the ICU was to be investigated. MATERIALS AND METHODS: I-FABP was measured in serum and urine of 43 critically ill patients in ICU when mesenteric ischemia was suspected. Bowel ischemia was confirmed in 21 patients (group 1). 22 patients who survived at least seven days without confirmation of ischemia were assigned to group 2. I-FABP levels were compared between the groups, and interval from the event that has triggered ischemia to I-FABP measurement was recorded. RESULTS: For the identification of patients with mesenteric ischemia, sensitivity, specificity, and area under the curve (AUC) for serum and urine I-FABP were 33.3%, 95.5%, and 0.565 and 81.3%, 70.0%, and 0.694, respectively. I-FABP measurements performed within 12 to 48 h after the event that triggered ischemia showed a sensitivity, specificity, and AUC for serum and urine of 75%, 100%, and 0.853 and 100%, 73.3%, and 0.856, respectively. CONCLUSIONS: In ICU patients, one single I-FABP measurement at the time of clinical suspicion failed to reliably detect or exclude mesenteric ischemia. A higher diagnostic value of I-FABP was only confirmed in the early stages of mesenteric ischemia. I-FABP may be used most appropriately in perioperative monitoring.

Surgery for colorectal cancer in elderly patients: how can we improve outcome?

PURPOSE: Patients over 70 years of age are characterised by diminished long-term survival rates following resection of colorectal cancer (CRC) compared to younger patients. The aim of this study was to clarify whether reduced survival is a result of malignancy, comorbidities or the treatment received. METHODS: All patients with CRC, who were admitted to our institution over a period of 10 years, were selected from a prospectively maintained database. Disease-specific, disease-free and overall survival rates were calculated dependent on variables considered potentially relevant for the patients' prognosis. RESULTS: 915 patients were included in the study. Observed 5- and 10-year survival rates for the whole group were 48 ± 2% and 40 ± 2%, respectively, but 10-year survival rates dropped to 14 ± 4% for patients aged 80 and older. Resection of the primary tumour was attempted in all cases independent of age. Emergency admission, Charlson index ≥2, ECOG ≥2, old age, second malignancies, distant metastases, high grading and non-resective surgery were identified as independent prognostic parameters associated with decreased overall survival. In contrast, disease-specific and disease-free survival rates for patients after elective radical resection in UICC-stage I-III did not show significant differences related to age. Tumour site, UICC-stage and resection status were independent statistically significant predictors of disease-specific survival. CONCLUSIONS: Similar disease-specific survival rates in all age groups speak in favour of tumour resection in curative intent even in old patients. Better outcome may be achieved, if regular screening for colorectal cancer is considered even in the elderly to avoid late presentation requiring emergency surgery.

Chemopreventive potential of in vitro fermented nuts in LT97 colon adenoma and primary epithelial colon cells.

Due to their beneficial nutritional profile the consumption of nuts contributes to a healthy diet and might reduce colon cancer risk. To get closer insights into potential mechanisms, the chemopreventive potential of different in vitro fermented nut varieties regarding the modulation of genes involved in detoxification (CAT, SOD2, GSTP1, GPx1) and cell cycle (p21, cyclin D2) as well as proliferation and apoptosis was examined in LT97 colon adenoma and primary epithelial colon cells. Fermentation supernatants (FS) of nuts significantly induced mRNA expression of CAT (up to 4.0-fold), SOD2 (up to 2.5-fold), and GSTP1 (up to 2.3-fold), while GPx1 expression was significantly reduced by all nut FS (0.8 fold on average). Levels of p21 mRNA were significantly enhanced (up to 2.6-fold), whereas all nut FS significantly decreased cyclin D2 expression (0.4-fold on average). In primary epithelial cells, expression of CAT (up to 3.5-fold), GSTP1 (up to 3.0-fold), and GPx1 (up to 3.9-fold) was increased, whereas p21 and cyclin D2 levels were not influenced. Nut FS significantly inhibited growth of LT97 cells and increased levels of early apoptotic cells (8.4% on average) and caspase 3 activity (4.6-fold on average), whereas caspase 3 activity was not modulated in primary colon cells. The differential modulation of genes involved in detoxification and cell cycle together with an inhibition of proliferation and induction of apoptosis in adenoma cells might contribute to chemopreventive effects of nuts regarding colon cancer.

Systematic classification of uterine cervical elongation in patients with pelvic organ prolapse.

OBJECTIVE: To define and classify cervical elongation, to compare uterine measurements after prolapse hysterectomy with a non-prolapse control group, and to associate stage of prolapse and degree of cervical elongation. STUDY DESIGN: This was a single-centre retrospective case-control study conducted at the University Hospital, Urogynaecological Unit, with a certified urogynaecological surgeon. Data were collected from patients with and without pelvic organ prolapse (POP) who underwent laparoscopically assisted vaginal hysterectomy. Post-hysterectomy uterine cervical elongation was examined using the corpus/cervix ratio (CCR), calculated from measurements taken on photographs. Cervical elongation was classified as physiological (grade 0, CCR>1.5) grade I (CCR>1 and ≤1.5) grade II (CCR>0.5 and ≤1), and grade III (CCR≤0.5). RESULTS: Cervical elongation was detected in 288/295 (97.6%) patients in the prolapse group (grade I, 44/288 [15.2%]; grade II, 212 [73.6%]; grade III, 32 [11.1%]). Mean CCR was greater among those with stage II/III than among those with stage IV prolapse (1.0±0.4 vs. 0.8±0.2; p<0.001). Grades of cervical elongation and prolapse stages were associated (p<0.001). Grade I cervical elongation was detected in 26/69 (37.6%), grade II in 5/69, and grade III in 0/69 patients of the control group. Cervical elongation was found more often in the prolapse group compared to the control group (p<0.001). Mean total uterine length did not differ between the prolapse and control groups (8.0±1.6 vs. 8.2±1.3cm), but mean calculated cervical length was greater in the prolapse group than in the control group (4.4±1.1 vs. 3.1+0.8cm; p<0.001). CONCLUSIONS: Uterine cervical elongation is found in patients undergoing hysterectomy for pelvic organ prolapse. Cervical elongation grades and prolapse stages are correlated. Defining uterine cervical elongation based on corpus/cervix ratio with grades I-III could be a valuable basic tool for further research.

Systematic assessment of surgical complications in 438 cases of vaginal native tissue repair for pelvic organ prolapse adopting Clavien-Dindo classification.

PURPOSE: To systematically review surgical complications of vaginal native tissue prolapse repair using Clavien-Dindo classification and to show whether concomitant surgery leads to increased complication rates. METHODS: Retrospective analysis of complications in 438 consecutive vaginal native tissue prolapse repairs and subgroup analysis was performed for concomitant hysterectomy or sacrospinous fixation for level I defects using Fisher's exact tests. RESULTS: Anterior and posterior colporrhaphia was performed in all 438 patients and sacrospinous fixation (SSF) for level I defects in 269 patients. Prolapse repair was combined with hysterectomy in 255 cases. One intra-operative bladder lesion (0.23%) and one rectal lesion (0.23%) occurred. Postoperative urinary tract infection requiring antibiotics was noted in 34 cases (7.8%). Post-void residual volume was medically treated in 24 cases (5.5%). Four patients (0.9%) underwent postoperative suprapubic catheter insertion. Asymptomatic gluteal hematomas were noted in 11 cases (2.5%). Four patients (0.9%) underwent re-operations for postoperative hemorrhage. Mean hospital stay was 5.6 days. Minor complications were classified as CD grade I in 2.5%, as CD grade II in 13.2%, complications requiring surgical intervention as grade IIIa in 0.9% and as grade IIIb in 0.9% of patients. No CD grade IV or V complications occurred. Apart from gluteal hematomas classified as CD grade I occurring in the SSF group (p = 0.019), no other differences of complication rates were found in the hysterectomy subgroup or in the SSF subgroup. CONCLUSION: Surgery was associated with low rate of CD grade III complications. Re-operation rate was 0.9%. The authors suggest introduction of CD classification for comparability of prolapse surgery.

Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.

The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.

Impact of butyrate on PKM2 and HSP90ß expression in human colon tissues of different transformation stages: a comparison of gene and protein data.

Due to protection of oncogenic proteins from degradation and enhancement of glycolytic phosphometabolites for synthetic processes, respectively, heat shock protein 90 (HSP90) and pyruvate kinase type M2 (PKM2) are important proteins for tumor growth. The present study was undertaken to investigate the susceptibility of both proteins and their encoding genes to the chemopreventive agent butyrate in human colon cells. Matched tissue of different transformation stages derived from 20 individual colon cancer patients was used for the experiments. The results of quantitative real-time PCR revealed a moderate increase of HSP90ß and PKM2 mRNA in colon tumors (P < 0.01) compared to normal tissues without relation to clinical parameters. The expression pattern could be confirmed for PKM2 protein by Western blot but not for HSP90ß. During culturing with butyrate, the amount of PKM2 transcripts decreased in all three tissue types with the strongest effects observed in tumors (median fold decrease 45%, P < 0.05). The protein data have not reflected this influence supposing a more gradual degradation rate due to a longer half-life of PKM2. In contrast, the mRNA expression of HSP90ß in normal tissue was found 1.38-fold increased by butyrate (P < 0.05), but not the corresponding protein level. HSP90ß expression in adenomas and tumors remained generally insensitive. Only in malignant tissue, however, a significant correlation was found between the individual effects observed on gene and protein expression level. In conclusion, the present study identified PKM2 as a potential direct target of butyrate in neoplastic colon tissue, whereas HSP90ß is none of it.