Sacral Neuromodulation Changes Pelvic Floor Activity in Overactive Bladder Patients-Possible New Insights in Mechanism of Action: A Pilot Study.

OBJECTIVES: To evaluate if electrodiagnostic tools can advance the understanding in the effect of sacral neuromodulation (SNM) on pelvic floor activity, more specifically if SNM induces changes in pelvic floor muscle (PFM) contraction. MATERIALS AND METHODS: Single tertiary center, prospective study (October 2017-May 2018) including patients with overactive bladder syndrome undergoing SNM. Electromyography of the PFM was recorded using the Multiple Array Probe Leiden. The procedure consisted of consecutive stimulations of the lead electrodes with increasing intensity (1-3, 5, 7, 10 V). Recordings were made after electrode placement (T0) and three weeks of SNM (T1). Patients with >50% improvement were defined as responders, others as nonresponders. For the analyses, the highest electrical PFM response (EPFMR), defined as the peak-to-peak amplitude of the muscle response, was identified for each intensity. The sensitivity (intensity where the first EPFMR was registered and the normalized EPFMR as percentage of maximum EPFMR) and the evolution (EMFPR changes over time) were analyzed using linear mixed models. RESULTS: Fourteen patients were analyzed (nine responders, five nonresponders). For nonresponders, the PFM was significantly less sensitive to stimulation after three weeks (T0: 1.7 V, T1: 2.6 V). The normalized EPFMR was (significantly) lower after three weeks for the ipsilateral side of the PFM for the clinically relevant voltages (1 V: 36%-23%; p = 0.024, 2 V: 56%-29%; p = 0.00001; 3 V: 63%-37%; p = 0.0002). For the nonresponders, the mean EPFMR was significantly lower at 8/12 locations at T1 (T0: 109 µV, T1: 58 µV; mean p = 0.013, range <0.0001-0.0867). For responders, the sensitivity and evolution did not change significantly. CONCLUSIONS: This is the first study to describe in detail the neurophysiological characteristics of the PFM, and the changes over time upon sacral spinal root stimulation, in responders and nonresponders to SNM. More research is needed to investigate the full potential of EPFMR as a response indicator.

Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial.

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy. METHODS: This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 × 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease-related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups. FINDINGS: Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 × 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity ≥grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed. INTERPRETATION: High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes.

Predictive potential of tumour-stroma ratio on benefit from adjuvant bevacizumab in high-risk stage II and stage III colon cancer.

BACKGROUND: The tumour-stroma ratio (TSR) has proven to be an independent prognostic factor in colon cancer. METHODS: Haematoxylin eosin tissue slides of patients from the AVANT trial were microscopically scored for TSR and categorised as stroma -low or stroma -high. Scores were correlated to the primary and secondary endpoint disease-free survival (DFS) and overall survival (OS). RESULTS: Patients with stroma-high tumours (N = 339, 28%) had a significantly shorter DFS (p < 0.001) compared to stroma-low tumours (N = 824, 68%). In the bevacizumab-FOLFOX-4 arm, DFS was significantly shorter compared to FOLFOX-4 in stroma-low tumours, with a hazard ratio (HR) of 1.94 (95% CI 1.24-3.04; p = 0.004). In stroma-high tumours a trend for better DFS was seen in bevacizumab-FOLFOX-4 vs. FOLFOX-4 (HR 0.61 (95% CI 0.35-1.07; p = 0.08)). For bevacizumab-XELOX vs. FOLFOX-4, this was not seen (stroma-low HR 1.07 (95% CI 0.64-1.77; p = 0.80); stroma-high HR 0.78 (95% CI 0.47-1.30; p = 0.35)). OS showed the same pattern for bevacizumab-FOLFOX-4 vs. FOLFOX-4 with a HR of 2.53 (95% CI 1.36-4.71; p = 0.003) for stroma-low and HR 0.50 (95% CI 0.22-1.14; p = 0.10) for stroma-high tumours. For bevacizumab-XELOX vs. FOLFOX-4, HR 1.13 (95% CI 0.55-2.31; p = 0.74) for stroma-low tumours and HR 0.74 (95% CI 0.37-1.51; p = 0.41) for stroma-high tumours. CONCLUSIONS: This exploratory analysis suggests a significantly shorter DFS and OS in stroma-low tumours with addition of bevacizumab to intravenous oxaliplatin-based chemotherapy, contrary to stroma-high tumours, where a beneficial trend is observed.

The effect of EMG biofeedback assisted pelvic floor muscle therapy on symptoms of the overactive bladder syndrome in women: A randomized controlled trial.

AIMS: The overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence. Biofeedback-assisted pelvic muscle therapy (BAPFMT) is a first-line treatment option for OAB. The aims of this study were to determine the efficacy and effectiveness of BAPFMT on symptoms of OAB after 9 weeks of treatment and to detect changes EMG activity of individual pelvic floor muscles (PFM) with the MAPLe. METHODS: Patients were randomly divided into an intervention group that received BAPFMT with the MAPLe or into a control group which received only toilet behavior and lifestyle instructions. The Pelvic Floor Inventories (PeLFIs), the King's Health Questionnaire (KHQ), a voiding dairy, a 24 h pad-test, and vaginal EMG registration of the pelvic floor with the MAPLe were used at inclusion and after 9 weeks follow-up to determine the effect of BAPFMT on complaints of OAB and Quality of Life (QoL). RESULTS: Fifty-eight patients were included. The PeLFIs, KHQ, voiding dairy, and 24 h pad-test showed significant improvements in the intervention group compared to the control group in complaints of OAB and QoL. EMG activity showed significant improvements for specific individual muscles at the different sides and depths for rest, maximal voluntary contraction, and endurance. CONCLUSIONS: EMG BAPFMT is effective in the OAB syndrome in women. It significantly reduces symptoms and complaints of OAB and increases QoL for patients. It shows that EMG changes in individual PFM, measured with the MAPLe, are relevant and related to symptom reduction.

Sling Surgery for the Treatment of Urinary Incontinence After Transurethral Resection of the Prostate: New Data on the Virtue Male Sling and an Evaluation of Literature.

OBJECTIVE: To provide a review of literature regarding the role of male slings in the treatment of stress urinary incontinence (SUI) following a transurethral resection of the prostate (TURP) and to evaluate the effects of the Virtue male sling in patients with post-TURP SUI. MATERIALS AND METHODS: A systematic review of literature was performed to identify all papers on the use of male slings in patients with post-TURP SUI. Second, a prospective cohort study was conducted on 8 patients who received the Virtue as surgical treatment of post-TURP SUI. Questionnaires were collected preoperatively and 1, 3, 6, and 12 months postoperatively. Success and improvement were defined as pad usage (0 pads: success, pad reduction of ≥50%: improvement). Primary end point was the continence rate 1 year postoperatively. Data were analyzed using the paired 2-tailed t test. RESULTS: Sling surgery appears to be significantly less successful in the treatment of SUI post TURP when compared to other types of prostate surgery. The clinical trial on the Virtue sling observed continence in 4 of 8 patients, with another 2 patients with improved continence after 1-year follow-up. No difference in success was observed between patients with mild and patients with severe SUI. CONCLUSIONS: Little is currently known about the effects of sling surgery in patients with mild to severe SUI following a TURP. Although the Virtue male sling seems to be an efficient and safe device in the treatment of this complication, longer follow-up and larger cohorts will be needed to further confirm these results.

Complementary Serologic Investigations in Children with Celiac Disease Is Unnecessary during Follow-Up.

OBJECTIVES: To determine the frequency of nutritional deficiencies and thyroid dysfunction in children with celiac disease (CD) and during follow-up after initiation of a gluten-free diet. Laboratory investigations of hemoglobin, ferritin, calcium, folate, vitamin B12, vitamin D, and thyroid function are regularly ordered in children with CD despite sufficient evidence for these. STUDY DESIGN: Between 2009 and 2014, test results of hemoglobin, ferritin, folate, vitamin B12, calcium, vitamin D (25[OH]D), free thyroxin, and thyroid stimulating hormone of children with CD regularly seen at the Leiden University Medical Center were investigated. Laboratory reference ranges were used to define abnormal results. Pearson χ(2) test for trend, unpaired t test, and 1-way ANOVA were used for statistical analysis. RESULTS: Of the 182 children evaluated, 119 were newly diagnosed. On average, 17% of results per year were missing because of incomplete blood investigations. Iron deficiency (28%) and iron deficiency anemia (9%) were found at the time of diagnosis of CD. Folate (14%), vitamin B12 (1%), and vitamin D deficiencies (27%) were also seen. No hypocalcemia or thyroid dysfunction was found. At follow-up, iron deficiency, iron deficiency anemia, and folate and vitamin D deficiency were observed in 8%, 2%, 3%, and 25% of patients, respectively. Vitamin B12 deficiency, hypocalcemia, and thyroid disease were not found. CONCLUSIONS: Complementary blood investigations are relevant at the time of diagnosis of CD but have little diagnostic yield during follow-up visits once the patient is placed on a gluten-free diet. Thus, we recommend that these variables only be assessed on indication, such as fatigue or abnormal growth.

Effect of preoperative pelvic floor muscle therapy with biofeedback versus standard care on stress urinary incontinence and quality of life in men undergoing laparoscopic radical prostatectomy: a randomised control trial.

AIMS: Laparoscopic radical prostatectomy (LARP) may cause stress urinary incontinence (SUI). This study reports the effects of preoperative pelvic floor muscle therapy (PFMT) on SUI and quality of life (QoL) in men undergoing LARP. MATERIALS AND METHODS: In this single-center randomized controlled trial, 122 patients undergoing LARP were assigned to an intervention group of PFMT with biofeedback once a week preoperatively, with 4 weeks' follow-up or to a control group receiving standard care. Randomization and allocation to the trial group were carried out by a central computer system. The primary analysis was based on 121 (n = 65; n = 56), comparing SUI rates and QoL in the two groups in a 1-year follow-up. Validated questionnaires, the Pelvic Floor Inventories (PeLFls), the King's Health Questionnaire (KHQ), the International Prostate Symptom Score (IPSS), a bladder diary, a 24-hr pad test and pelvic floor examination were used. Continence was defined as no leakage at all. All analyses were performed according to intention-to-treat. RESULTS: One hundred twenty-two patients were randomized, 19 patients were excluded from analysis because of early drop-out. There were no significant differences between both groups in the incidence of SUI and QoL based on the KHQ, IPSS, and pad tests (P ≥ 0.05). In all patients continence was achieved in 77.2% at 1 year postoperatively. CONCLUSIONS: Preoperative PFMT does not appear to be effective in the prevention of SUI and QoL following LARP.

Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: a double-blind randomized placebo-controlled trial in long-term care facilities.

OBJECTIVES: To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. DESIGN: Double-blind randomized placebo-controlled multicenter trial. SETTING: Long-term care facilities (LTCFs). PARTICIPANTS: LTCF residents (N = 928; 703 women, median age 84). MEASUREMENTS: Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥ 1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. RESULTS: In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57-0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68-1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). CONCLUSION: In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk.

Cost-effectiveness of cranberry capsules to prevent urinary tract infection in long-term care facilities: economic evaluation with a randomized controlled trial.

OBJECTIVES: To investigate whether the preventive use of cranberry capsules in long-term care facility (LTCF) residents is cost-effective depending on urinary tract infection (UTI) risk. DESIGN: Economic evaluation with a randomized controlled trial. SETTING: Long-term care facilities. PARTICIPANTS: LTCF residents (N = 928, 703 female, median age 84), stratified according to UTI risk. MEASUREMENTS: UTI incidence (clinically or strictly defined), survival, quality of life, quality-adjusted life years (QALYs), and costs. RESULTS: In the weeks after a clinical UTI, participants showed a significant but moderate deterioration in quality of life, survival, care dependency, and costs. In high-UTI-risk participants, cranberry costs were estimated at €439 per year (1.00 euro = 1.37 U.S. dollar), which is €3,800 per prevented clinically defined UTI (95% confidence interval = €1,300-infinity). Using the strict UTI definition, the use of cranberry increased costs without preventing UTIs. Taking cranberry capsules had a 22% probability of being cost-effective compared with placebo (at a willingness to pay of €40,000 per QALY). In low-UTI-risk participants, use of cranberry capsules was only 3% likely to be cost-effective. CONCLUSION: In high-UTI-risk residents, taking cranberry capsules may be effective in preventing UTIs but is not likely to be cost-effective in the investigated dosage, frequency, and setting. In low-UTI-risk LTCF residents, taking cranberry capsules twice daily is neither effective nor cost-effective.

Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial.

Musculoskeletal adverse events (MSAEs) and vasomotor symptoms (VMSs) are known side-effects of aromatase inhibitors, and may be related to genetic variations of the aromatase gene (CYP19A1). We investigated the relationship between these specific AEs and single nucleotide polymorphisms (SNPs) in the CYP19A1 gene in postmenopausal, hormone receptor-positive early breast cancer (BC) patients treated with adjuvant exemestane for 5 years. Dutch patients who were randomized to receive 5 years of exemestane in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. A tagging-SNP approach was performed, covering 80 % of variations of the CYP19A1 gene with 30 SNPs. Logistic regression analyses were used to assess the risk of reporting VMSs or MSAEs in relation to genotypes within selected SNPs. Of 737 included patients, 281 patients reported at least one MSAE (n = 210) or VMS (n = 163). Homozygous AA genotype of rs934635 was associated with a significantly higher odds of MSAEs (multivariate odds ratio (OR) 4.66, p = 0.008) and VMSs (multivariate OR 2.78, p = 0.044). Regarding both rs1694189 and rs7176005, the homozygous variant genotypes (TT) were associated with a higher odds of VMSs, but not MSAEs (OR 1.758, p = 0.025 and OR 6.361, p = 0.021, respectively). Our exploratory analysis demonstrated that some CYP19A1 gene variations may be associated with MSAEs and/or VMSs. Specifically, patients with the homozygous variant rs934635 genotype reported more MSAEs and VMSs. Although further confirmatory studies are warranted, genomic profiling can help identify patients at an increased risk of reporting these specific AEs, potentiating further personalized BC treatment.

Sexual abuse history in GI illness, how do gastroenterologists deal with it?

INTRODUCTION: Data support an increased prevalence of sexual abuse (SA) among patients with gastrointestinal (GI) complaints. Sexual abuse causes multiple symptoms related to pelvic floor and stress mediated brain-gut dysfunctions. Treating these patients asks for a holistic approach, using centrally targeted interventions. However, gastroenterologists have never been surveyed regarding their practice patterns and constraints about inquiring into SA. AIM: To evaluate whether gastroenterologists address SA in their daily practice and to evaluate their knowledge regarding the implications of SA in GI illness. METHODS: A 42-item anonymous questionnaire was mailed to all 402 members of the Dutch Society of Gastroenterology (gastroenterologists and fellows in training). The questionnaire addressed SA and pelvic-floor-related complaints. MAIN OUTCOME MEASURES: The results of this survey. RESULTS: One hundred eighty-three of the 402 (45.2%) questionnaires were returned. Overall, 4.7% of the respondents asked their female patients regularly about SA; in males, this percentage was 0.6%. Before performing a colonoscopy, these percentages were even smaller (2.4% and 0.6%, respectively). When patients presented with specific complaints, such as chronic abdominal pain or fecal incontinence, 68% of the gastroenterologists asked females about SA and 29% of the males (P < 0.01). The majority of respondents stated it as rather important to receive more training on how to inquire about SA and its implications for treatment. CONCLUSION: Gastroenterologists do not routinely inquire about a history of SA and they rarely ask about it before performing colonoscopy. There is a need for training to acquire the skills and knowledge to deal with SA.

Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS).

BACKGROUND: Radical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively. METHODS/DESIGN: In this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate. CONCLUSION: Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer. TRIAL REGISTRATION: clinicaltrials.gov NCT00407186.

ECG identification of scar-related ventricular tachycardia with a left bundle-branch block configuration.

BACKGROUND: A left bundle-branch block (LBBB)-like pattern with a dominant S-wave in V(1) is common in idiopathic ventricular arrhythmias (VA). Discrimination between idiopathic and scar-related LBBB pattern VA has important clinical implications. We hypothesized that the VA QRS morphology is influenced by the presence of ventricular scar, allowing ECG discrimination of VA arising from structurally normal versus scarred myocardium. METHODS AND RESULTS: Twelve-lead ECGs of 297 LBBB pattern monomorphic VA were recorded during catheter ablation procedures. QRS morphology characteristics associated with scar-related VA were identified in retrospective analysis of 118 LBBB pattern VA (95 scar-related, 23 idiopathic) to develop a stepwise algorithm that was prospectively tested in 179 LBBB pattern VA (120 scar-related, 59 idiopathic). The diagnosis of scar was based on sinus rhythm surface ECG, cardiovascular imaging, and electroanatomic catheter mapping. A precordial transition beyond V4, notching of the S-wave downstroke in lead V1 or V2, and a duration from the onset of QRS to the S-nadir in V1 >90 ms were independent predictors for scar-related VA. The proposed algorithm classified a VA as scar-related if any of these criteria was met. If none of the criteria was present, a VA was classified as idiopathic. In prospective validation, the algorithm was highly sensitive (96%) and specific (83%) for the identification of scar-related LBBB pattern VA. CONCLUSIONS: The QRS morphology of VA is different between scar-related and idiopathic VA. A simple ECG algorithm is sensitive for identifying scar-related LBBB VA, which could be helpful in guiding further evaluation of these patients.

Reversed polarity of bipolar electrograms for predicting a successful ablation site in focal idiopathic right ventricular outflow tract arrhythmias.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for idiopathic right ventricular outflow tract (RVOT) arrhythmias is typically guided by local activation time (LAT) mapping and unipolar electrogram morphology (QS configuration). However, LAT mapping is limited by the large variation among patients, and the area demonstrating a QS configuration of the unipolar electrogram may be larger than the focal source. Reversed polarity has been proposed as a criterion for guiding RFCA. OBJECTIVE: The purpose of this study was to investigate the value of reversed polarity of adjacent bipolar electrograms for predicting a successful ablation site in idiopathic RVOT arrhythmias. METHODS: Twenty-five consecutive patients (12 men [48%], age 43 ± 15 years) undergoing RFCA for RVOT arrhythmia were studied. Electrograms of ablation sites and of points within a 15-mm radius to the successful site were evaluated for LAT, unipolar electrogram morphology, and the presence of reversed polarity of adjacent bipolar electrograms. Electrogram characteristics of successful ablation sites were compared to those of nonsuccessful ablation sites. The spatial distribution of each electrogram characteristic was studied. RESULTS: Successful ablation sites more often demonstrated reversed polarity and had an earlier LAT than nonsuccessful sites. A wide spatial distribution was observed for unipolar electrograms with a QS configuration around the successful ablation site. Mapping based on LAT and reversed polarity had a higher predictive value for a successful ablation site than mapping based on LAT and QS configuration. CONCLUSION: The presence of reversed polarity has a high predictive value for successful ablation sites in focal idiopathic RVOT arrhythmias and is likely to reduce the number of RFCA applications.

Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer.

PURPOSE: The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy. PATIENTS AND METHODS: Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns. RESULTS: With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P = .0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P = .001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival. CONCLUSION: After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.

Improved overall survival for patients with rectal cancer since 1990: the effects of TME surgery and pre-operative radiotherapy.

AIM: The aim was to study the effects of the introduction of TME surgery and pre-operative radiotherapy on overall survival (OS) by comparing patients treated in the period before (1990-1995), during (1996-1999) and after (2000-2002) the TME trial. PATIENTS AND METHODS: Patients diagnosed with rectal carcinoma in the region of Comprehensive Cancer Centres South and West were used (n=3179). RESULTS: Five-year OS was, respectively, 56%, 62% and 65% in the pre-trial, trial and post-trial periods (p<0.001). Pre-operative RT was increasingly used over time and significantly related to OS in the post-trial period (p=0.002), but not in the pre-trial and trial periods. CONCLUSIONS: Population-based OS improved markedly since the introduction of TME surgery. With standardised TME surgery, pre-operative RT improved OS, whereas withholding pre-operative RT was associated with a poorer prognosis. The present study supports that pre-operative RT was correctly introduced as a standard treatment before TME surgery in our national guideline.

Cutaneous and intra-abdominal abscess formation in rats following radio frequency [corrected] ablation of liver tumors in combination with celecoxib treatment.

BACKGROUND: The present study evaluated the safety of treatment of colorectal liver metastases with radio frequency ablation (RFA) in combination with high doses of the selective cyclooxygenase-2 inhibitor celecoxib. MATERIALS AND METHODS: The study was performed in the CC531 rat model for colorectal cancer. The rats were inoculated with CC531 tumor cells subcapsularly in the liver. They were then randomized for treatment with celecoxib, RFA, or their combination. Celecoxib treatment was started at tumor induction. Three weeks later the liver tumors were treated with RFA and the effects on the health of the rats were monitored. RESULTS: Treatment that included RFA resulted in significantly (p=0.003) more deaths than sham-operated rats. Including celecoxib in the treatment resulted in significantly increased cutaneous wound abscess formation after surgery (p<0.0001). In addition, the combination of celecoxib treatment with RFA resulted in intra-abdominal abscess formation (p<0.0001). CONCLUSION: The results indicated that the combination of high-dose celecoxib and RFA for treating liver metastases should be used with caution when applied as an anticancer treatment modality since additional side-effects are induced.