Low anterior resection syndrome (LARS) in ovarian cancer patients - A multi-centre comparative cohort study.

BACKGROUND: Low anterior resection syndrome (LARS) is a common functional disorder after low anterior resection impacting the quality of life. Data on LARS derives nearly exclusively from rectal cancer studies. Therefore, the study was designed to assess LARS in advanced epithelial ovarian cancer (EOC) patients, who underwent rectal resection and to compare it with a female rectal cancer cohort. MATERIAL AND METHODS: A cross-sectional multi-centre analysis was performed on female patients suffering from either rectal or EOC who received a low anterior resection as part of their therapy regimen. None of the patients received pre- or postoperative radiotherapy. LARS was defined by using the validated LARS score and its severity was divided into "no", "minor" and "major LARS". RESULTS: In total, 125 female patients (44.8% (n = 56) EOC vs. 55.2% (n = 69) rectal cancer patients) met the final inclusion criteria and were retrospectively analyzed. Baseline characteristics were comparable between the groups. Median follow-up was 22 (IQR 12-56) months. In total, 30.4% (n = 38) of the patient group reported bowel dysfunction after surgery. Rates of LARS were not significantly different between EOC and rectal cancer patients (major LARS 16.1% (n = 9) vs. 15.9% (n = 11); minor LARS 17.9% (n = 10) vs. 11.6% (n = 8); p = 0.984). The time interval between surgery and final assessment had no impact on the postoperative bowel function (p = 0.820). CONCLUSION: LARS is a frequent and highly underreported postoperative disorder in EOC patients who require cytoreductive surgery with rectal resection. The functional outcome is comparable to female patients with rectal cancer who underwent low anterior resection without receiving radiotherapy.

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray.

BACKGROUND: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA). METHODS: A total of 75 RC patients (60 irradiated, 15 treatment-naïve) were defined for retrospective analysis. RC samples were processed for immunohistochemistry (CD3, CD8, PD-1, PD-L1). Analogue (score 0-3) as well as digital quantification (TMA: 2 cores vs. 6 cores, mean T cell count) of marker expression in 2 areas (central tumor, CT; invasive margin, IM) was performed. Survival was estimated on the basis of analogue as well as digital marker densities calculated from 2 cores (Immunoscore: CD3/CD8 ratio) and 6 cores per tumor area. RESULTS: Irradiated RC samples showed a significant decrease in CD3 and CD8 positive T cells, independent of quantification mode. T cell densities of 6 virtual cores approximated to T cell densities of full tissue sections, independent of individual core density or location. Survival analysis based on full tissue section quantification demonstrated that CD3 and CD8 positive T cells as well as PD-1 positive tumor infiltrating leucocytes (TILs) in the CT and the IM had a significant impact on disease-free survival (DFS) as well as overall survival (OS). In addition, CD3 and CD8 positive T cells as well as PD-1 positive TILs in the IM proved as independent prognostic factors for DFS and OS; in the CT, PD-1 positive TILs predicted DFS and CD3 and CD8 positive T cells as well as PD-1 positive TILs predicted OS. Survival analysis based on virtual TMA showed no impact on DFS or OS. CONCLUSION: Spatial tumor heterogeneity might result in inadequate quantification of immune marker expression; however, if using a TMA, 6 cores per tumor area and patient sample represent comparable amounts of T cell densities to those quantified on full tissue sections. Consistently, the tissue area used for immune marker quantification represents a crucial factor for the evaluation of prognostic and predictive biomarker potential.

Laparoscopic transperitoneal and retroperitoneal adrenalectomy: a 20-year, single-institution experience with an analysis of the learning curve and tumor size [lap transper and retroper adrenalectomy].

BACKGROUND: The superiority of laparoscopic transperitoneal (TP) versus retroperitoneal (RP) adrenalectomy is an ongoing debate. METHODS: Data from 163 patients (TP: n = 135; RP: n = 28) undergoing minimally invasive adrenalectomy were analyzed. Both operative [intraoperative blood loss, previous abdominal surgery, conversion rate, operative time and tumor size] and perioperative [BMI (body mass index), ASA (American Society of Anesthesiologists) score, time of hospitalization, time of oral intake, histology and postoperative complications] parameters were compared. Both the learning curve (LC) and tumor size were analyzed. RESULTS: We found significant differences in the mean operative time (p = 0.019) and rate of previous abdominal surgery (p = 0.038) in favor of TP. Significantly larger tumors were removed with TP (p = 0.018). Conversion rates showed no significant difference (p = 0.257). Also, no significant differences were noted for time of hospitalization, intraoperative blood loss and postoperative complications. In terms of the LC, we saw significant differences in previous abdominal surgery (p = 0.015), conversion rate (p = 0.011) and operative time (p = 0.023) in favor of TP. Large (LT) and extra-large tumors (ELT) were involved in 47 lesions (LT: 40 vs. ELT: 7), with a mean tumor size of 71.85 and 141.57 mm, respectively. Mean intraoperative blood loss was 64.47 ml vs. 71.85 ml, time of hospitalization was 5.10 vs. 4.57 days and mean operative time was 76.52 vs. 79.28 min for LT and ELT, respectively. CONCLUSION: A shorter operative time and lower conversion rate in favor of TP were noted during the learning curve. TP proved to be more effective in the removal of large-, extra-large and malignant lesions. The RP approach was feasible for smaller, benign lesions, with a more prolonged learning curve.

Let us integrate sexual health-do psychiatrists integrate sexual health in patient management?

The high prevalence of sexual dysfunction and the importance of sexual health issues in general stress the need for a physician to integrate sexual health issues in patient management. In this study, we evaluate the frequency of psychiatrists addressing sexual health issues as well as their attitude towards sexual health. Plus, we want to evaluate the multi-professional network for patient treatment that is needed by physicians for collaboration with other medical specialists and health care professionals. At total 100 psychiatrists (age range 30-60 years), participating at the annual meeting of the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics, were invited to self-assess their caring for patients' sexual health issues and answer a self-report questionnaire. The return rate was 74%. A third of the participating psychiatrists and psychotherapists stated to address sexual health in patients in daily routine. Twenty-five percent of the physicians suspected sexual health problems in 60-100% of their patients but did not ask the patients about this topic. Mentioned reasons why patients would not actively address sexual problems were rated by the survey participants "a different problem was more important", "lack of time", and "embarrassment". Only few of the participating psychiatrists stated to offer a consultation in sexual health to the patients, none to offer sexual therapy. A mentioned reason was "lack of competence regarding sexual health". Twelve percent referred the patients with sexual issues to a physician with another medical specialization, especially to experts in gynaecology and obstetrics, to experts in urology, or to andrologists. However, a need for a network in the field of sexual medicine was stated and an unawareness of a sexual health care network: where to refer the patients in need. Our data showed an increased need in the routine treatment and management of sexual health care in psychiatrists and psychotherapists. Plus, the data stresses the need for professional sexual medicine qualification and for extended cooperation between different medical fields and health care professionals in order to integrate sexual health topics professionally in daily routine.

TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

TP53 germline mutation may affect response to anticancer treatments: analysis of an intensively treated Li-Fraumeni family.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited disorder associated with the occurrence of a wide spectrum of early-onset malignancies, the most prevalent being breast cancer and sarcoma. The presence of TP53 germline mutations in the majority of LFS patients suggests a genetic basis for the cancer predisposition. No special recommendations for the treatment of LFS patients have been made to date, except that of minimizing radiation. We hypothesized that TP53 germline mutations may be associated not only with cancer predisposition, but also with lack of response to chemo- and radiotherapy. Here, we present an Austrian LFS family whose members were intensively treated with chemo- and radiotherapy due to cancers that occurred at a predominantly young age, including eight breast cancers in six patients. Material from seven family members was screened for p53 mutation by Sanger sequencing and immunohistochemistry. A rare missense mutation in the tetramerization domain of exon 10 of the TP53 gene was found to segregate with malignant disease in this family. Lack of response to various chemotherapies and radiotherapy could be ascertained by histopathology of surgical specimens after neoadjuvant treatment, by cancer relapse occurring while receiving adjuvant systemic treatment and by the occurrence of second primaries in areas of adjuvant radiation. Our observations suggest that current standards of cancer treatment may not be valid for patients with LFS. In patients with TP53 germline mutation, cytotoxic treatment may bear not only the risk of tumor induction but also the risk of treatment failure.

New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology.

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer.

BACKGROUND: Neoadjuvant chemotherapy can facilitate pancreatic resection in patients with initially unresectable pancreatic cancer (PC). We report the results of a phase II trial of gemcitabine-oxaliplatin neoadjuvant chemotherapy for patients with locally advanced, nonmetastatic PC. METHODS: A prospective, phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine (900 mg/m(2)) and oxaliplatin (60 mg/m(2)) given as intravenous infusion once a week at day 1 of each treatment cycle (NeoGemOx protocol). Patients received 6-9 cycles of chemotherapy. Those patients with sufficient tumor regression subsequently underwent pancreatic resection and were followed postoperatively to assess long-term survival. RESULTS: A total of 33 patients were eligible and were included in the intent-to-treat and evaluable population. On centralized review of the imaging studies, 18 patients had unresectable disease at inclusion, and 15 patients had borderline resectable PC. Eventually, 13 patients (39%) had a curative resection after neoadjuvant therapy. The R0 resection rate was 69%. Median overall survival of patients who underwent tumor resection was 22 months (95% confidence interval [CI], 14-30) compared with 12 months (95% CI, 9-15) for those without resection (P = .046). The median recurrence-free survival rate after resection was 10 months (95% CI, 4-17). CONCLUSION: Neoadjuvant gemcitabine plus oxaliplatin is well tolerated and safe. Substantive tumor regression occurs in some patients with locally advanced PC treated with this neoadjuvant protocol, offering the potential for curative resection and improvement in overall survival. Additional studies involving the NeoGemOx protocol should be considered to further evaluate the safety and efficacy of this combination.

Long-term anorectal and sexual function after overlapping anterior anal sphincter repair: a case-match study.

PURPOSE: The purpose of this study was to assess the impact of overlapping anal sphincter repair for fecal incontinence on overall pelvic organ function. METHODS: This study was a case-match study of 25 women undergoing overlapping anal sphincter repair from 1996 through 2003. Functional outcome was assessed using validated scoring systems. For each case, two controls matched for age and parity were assessed. RESULTS: Twenty-one patients responded to the questionnaires; mean follow-up time was 105 (SD, 33.6) months. Analyzing the Wexner incontinence score, the group median improved from 15 (range, 4-20) before the procedure to 8 (range, 2-18; P < 0.001) at follow-up.Conversely, postoperatively there was no difference in symptoms of urinary incontinence between groups. The Female Sexual Function Index of case patients was significantly lower than that of control patients (cases, 16.2 [2.3-33.6]; controls, 26.1 [3.3-36]; P = 0.004). The Short-Form-12 physical health score was similar for both groups (mean +/- standard deviation: cases, 46.1 +/- 10.8; controls, 48.6 +/- 11.4; P = 0.220), whereas the mental health score of patients was significantly lower than that of controls (cases, 39.8 +/- 10.5; controls, 47.1 +/- 8.5; P = 0.0057). CONCLUSION: Anal sphincter repair for localized sphincter defects may achieve excellent/good long-term functional results in 67 percent of patients, as judged by patients. Despite repair, continence remained significantly inferior in patients as compared with healthy control subjects. In addition, sexual function was significantly diminished in patients as compared with controls, but no correlation with the severity of fecal incontinence was found.

Endorectal advancement flaps in the treatment of high anal fistula of cryptoglandular origin: full-thickness vs. mucosal-rectum flaps.

PURPOSE: The treatment of high anal fistula using endorectal advancement flaps represents an important technique to attain cure of fistulation and preserve anal continence. The creation of the advancement flap may comprise the rectal mucosa only or involve the full transection of the rectal wall. A comparison between full-thickness flaps and mucosal (partial-thickness) flaps was made to analyze the defining elements of successful fistula treatment: recurrence rates and anal continence. METHODS: A retrospective review of 54 consecutive patients with high anal fistula of cryptoglandular origin was undertaken. Patient risk was categorized according to previous anal surgery. Continence was assessed according to the Vaizey score. Recurrence rates were recorded in a long-term, complete follow-up. RESULTS: Thirty-four patients underwent surgery using a partial-thickness flap; in 20 patients the full-thickness flap was used. There were no major intraoperative or postoperative complications. Continence scores revealed significant incontinence in 11.1 percent of all patients. Full transection of the rectal wall for flap creation did not pose a threat to continence. Twenty-four percent of all patients suffered from a recurrence. Patients with four or more previous anal surgeries were at highest risk for failure. A single patient in the full-thickness flap group (5 percent) as opposed to 12 patients (35.3 percent) in the partial-thickness group suffered from recurrence. CONCLUSION: The comparison of partial-thickness to full-thickness endorectal advancement flaps suggests an improvement of recurrence rates without higher incontinence rates when a full mobilization of the rectal wall is performed.

Infliximab: lack of efficacy on perforating complications in Crohn's disease.

BACKGROUND: Infliximab (Remicade), a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), has emerged as promising therapeutic option in perianal fistulizing Crohn's disease (CD). However, little knowledge exists about its use for the treatment of internal fistulas in CD. We present our experience with infliximab in this situation. METHODS: Four patients with CD who had internal fistulas (Case 1: entero-enteral and entero-abdominal; Case 2: entero-enteral; Case 3: entero-enteral and parastomal; Case 4: entero-vesical) were treated with 3 infusions of infliximab (5 mg/kg body weight) with intervals of 2 and 4 weeks. In addition, 3 patients had strictures and 2 patients had perianal fistulas. RESULTS: After the three infusions of infliximab (5 mg/kg body weight), internal fistulas remained unchanged in all patients. The perianal fistulas present in 2 cases were healed. Administration of infliximab was safe and well tolerated in all cases. CONCLUSION: Treatment with 3 infusions of infliximab (5 mg/kg body weight) led to healing of only the perianal fistulas, whereas the internal fistulas were not influenced. We conclude that in these 4 cases, infliximab was well tolerated but not effective for the management of internal fistulas and was no alternative for surgery.

Dedicated multidetector CT of the stomach: spectrum of diseases.

Multidetector computed tomography (CT) offers new opportunities in imaging of the gastrointestinal tract. When thin collimation is used, near-isotropic imaging of the stomach is possible, allowing high-quality multiplanar reformation and three-dimensional reconstruction of gastric images. Proper distention of the stomach and optimally timed administration of intravenous contrast material are required to detect and characterize disease. In contrast to gastroscopy and double-contrast studies of the stomach, CT provides information about both the gastric wall and the extragastric extent of disease. Preoperative staging of gastric carcinoma appears to be the main clinical indication for multidetector CT. In addition, multidetector CT allows detection of other gastric malignancies (lymphoma, carcinoid tumors, metastases, gastrointestinal stromal tumors) and benign gastric tumors (neural tumors, polyps). Gastric inflammation (gastritis, ulcers, Ménétrier disease) and miscellaneous gastric conditions (emphysema, gastric outlet obstruction, varices) can also be visualized with multidetector CT. Multidetector CT is a valuable tool for the evaluation of gastric wall disease and serves as an adjunct to endoscopy.

TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer.

OBJECTIVE: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer. SUMMARY BACKGROUND DATA: Recent studies show that p53 may be a determinant of radiosensitivity being required for induction of apoptosis in case of radiation-induced DNA damage. METHODS: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively. RESULTS: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51. CONCLUSIONS: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.