Quality of life and functional outcomes after transanal total mesorectal excision for rectal cancer-results from the implementation period in Denmark.

BACKGROUND: The standard operation for mid- and low rectal cancer total mesorectal excision (TME) is routinely performed as minimally invasive surgery. TME is associated with temporary or permanent functional impairment of pelvic organs, causing reduced quality of life (QoL). Concerns have been raised that the newest minimally invasive approach, transanal TME (TaTME), may further reduce urogenital and anorectal functions. OBJECTIVE: To determine if functional outcomes affecting QoL are altered after TaTME. Primary end-point is the impact of TaTME on QoL and functional outcomes. Secondary end-point is assessing differences in QoL and functional outcomes after TME surgery from below (TaTME) or above (transabdominal TME). DESIGN, SETTING, AND PARTICIPANTS: Observational study consisting of prospectively registered self-reported questionnaire data collected at baseline and follow-ups after TaTME. All patients who underwent TaTME during the Danish national implementation phase were included. Central surveillance of the implementation included questionnaires concerning QoL and functional outcomes. Analyses of functional results from the Danish cohort of the ROLARR trial (Jayne et al. in JAMA 318:1569-1580, (2017) are reported separately for perspective, representing the transabdominal approach to TME, i.e., laparoscopic- or robotic-assisted TME (LaTME/RoTME). Applied questionnaires include EORTC QLQ-C30, SF-36, LARS, ICIQ-MLUTS, ICIQ-FLUTS, IPSS, IIEF, SVQ, and FSFI. RESULTS: A total of 115 TaTME procedures were registered August 2016 to April 2019. LaTME/RoTME patients (n = 92) were operated on January 2011 to September 2014. A temporary postoperative decrease of QoL (global health status and functional scales) was observed, yet long-term results were unaffected by surgery in both groups. In TaTME patients, the anorectal dysfunction increased significantly (p < 0.001) from preoperative baseline to 13.5 months follow-up, where 67.5% (n = 52) reported major LARS symptoms. Urinary function was not significantly impaired after TME regardless of technique. The paucity of responses concerning sexual function precludes conclusions. CONCLUSIONS: Although an initial reduction in QoL after TME occurs, it normalizes within the first year postoperatively. In concurrence with international results, we found that significant anorectal dysfunction is common after TaTME. No data on anorectal function was available for LaTME/RoTME patients for comparison. We found no indications that transanal TME is inferior to transabdominal TME surgery concerning urogenital functions or health-related QoL.

Validation of the Danish Colorectal Cancer Group (DCCG.dk) database - on behalf of the Danish Colorectal Cancer Group.

AIM: The aim of this study was to validate the clinical quality database of the Danish Colorectal Cancer Group. The validation is meant to focus on core data regarding staging of the disease, treatment provided, patient-related factors and key complications. METHOD: This was a database validation study assessing the completeness of the database and the accuracy of the data by re-entering core variables into an online module in a blinded fashion and comparing re-entered data with the original database data. A sample of 5% of patients from the years 2014-2017 was randomly selected. RESULTS: The sample of 936 patients was identified and data were re-entered. The completeness of the data retrieved was a median of 96%, 100% and 99% for preoperative, intra-operative and postoperative variables, respectively. The overall accuracy was a median of 95%. The least accurate variable was date of diagnosis (50% perfect agreement), with agreement rising to 96% when near matches defined as correct date ± 30 days were included. Intra-operative variables were of high quality, as were data on surgical complications including anastomotic leakage, where agreement was 97%. CONCLUSION: This was the first major validation of the Danish Colorectal Cancer Group's database. Overall, the completeness and quality of data were high, but the validation process also identified weaknesses, which can be crucial for future users to acknowledge and consider.

Outcome following local excision of T1 anal cancers-a systematic review.

PURPOSE: In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low recurrence rates. However, chemo-radiotherapy has several side effects: dyspareunia, impotence, fecal incontinence, pain, and skin symptoms. Small/T1 tumors, without metastatic disease, can be treated with local excision alone. We aimed to systematically review the literature regarding outcome following local excision of T1 SCCA. METHODS: PubMed and Embase databases were searched for studies that investigated outcome following local excision of SCCA. RESULTS: Twenty-three studies were included. Twenty of the studies were retrospective, and three studies included more than 100 patients. Most of the studies were published before the 1980s. Overall there was great heterogeneity and missing data across the included studies when comparing patient demographics, resection margins, definitions on tumor location, and outcome. Overall 5-year survival was 69% (95% CI 66-72) following local excision. Overall 5-year recurrence was 37% (95% CI 30-45) following local excision. No complications were reported following local excision. CONCLUSION: The current literature on outcome following local excision of T1 anal cancers consists predominantly of smaller, retrospective, and heterogenous studies. Overall 5-year survival is acceptable, but worse than following chemo-radiation therapy. However, local excision seems to have no or only few minor complications. Recurrence rates are high. Therefore, a thorough follow-up program is needed when performing local excision as primary treatment for T1 SCCA. There is an evident need for further studies.

Quality of life following salvage surgery for squamous cell carcinoma of the anus.

INTRODUCTION: Squamous cell carcinoma of the anus is a rare condition. First line treatment is combined chemo-radio therapy. As many as a third of patients undergoing chemo-radiotherapy will experience recurrence. These patients often undergo salvage surgery with an extended abdominoperineal excision. The aim of this study was to examine the quality of life in disease free survivors following salvage surgery for squamous cell carcinoma of the anus. MATERIAL AND METHODS: Patients undergoing salvage surgery for SCCA at Copenhagen University Hospital Herlev between 1st of January 2011 and 31st December 2016 were identified and quality of life was assessed with EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. RESULTS: 47 patients underwent salvage surgery for relapse or residual tumor in the period. From this cohort 25 disease-free survivors were identified. Fourteen (56%) patients returned a completed questionnaire. Overall median global health status was 75(range 20-100). Functional scores were generally high. In General, symptom scores were low, however all men reported impotence with a median symptom score of 100(range 67-100) and half the women reported dyspareunia. Urinary impairment was present in half the patients. Abdominal and buttock pain scores were low. CONCLUSION: Quality of life following salvage surgery for squamous cell carcinoma of the anus is affected but at an acceptable level. However, there are considerable side-affects in the form of impotence, dyspareunia and urinary impairment.

30-day and long-term outcome following salvage surgery for squamous cell carcinoma of the anus.

INTRODUCTION: Squamous cell carcinoma of the anus (SCCA) is a rare condition. First line treatment is combined chemo-radio therapy. As many as a third of patients undergoing CRT will experience recurrence. These patients often undergo salvage surgery with an extended abdominoperineal excision. The aims of this study were 1) to assess and evaluate 30-day postoperative morbidity and mortality after salvage surgery for recurrent SCCA, and furthermore, 2) to examine secondary recurrence and long-term mortality after salvage surgery for recurrent SCCA. MATERIAL AND METHODS: Retrospective evaluation of all patients undergoing salvage surgery for SCCA at Copenhagen University Hospital Herlev between 1st of January 2011 and 31th December 2016. RESULTS: Forty-seven patients were identified. 30-day postoperative mortality was 4%. The most common postoperative complication was perineal wound defects. Within the follow-up period of median 20 (1-80) months, secondary recurrence occurred in 30% of patients. Median disease free survival was 32 months. Secondary recurrence was significantly more frequent in patients with R1 resection and pN ≥ 1. Within the follow-up period of median 25 (0-80) months, mortality was 40%. Overall median survival was 39 months. Secondary recurrence was associated with a significantly higher risk of death within the follow-up period. CONCLUSION: Salvage surgery for relapse of squamous cell carcinoma of the anus is a safe procedure with a good short-term outcome. Secondary recurrence was more frequent in patients with R1-resection and pN ≥ 1. More than one third of the patients died within the follow-up period, and mortality was significantly higher in the group of patients with secondary recurrence.

Low-energy electron scattering in carbon-based materials analyzed by scanning transmission electron microscopy and its application to sample thickness determination.

High-angle annular dark-field scanning transmission electron microscopy (HAADF STEM) at low energies (≤30 keV) was used to study quantitatively electron scattering in amorphous carbon and carbon-based materials. Experimental HAADF STEM intensities from samples with well-known composition and thickness are compared with results of Monte Carlo simulations and semiempirical equations describing multiple electron scattering. A well-defined relationship is found between the maximum HAADF STEM intensity and sample thickness which is exploited (a) to derive a quantitative description for the mean quadratic scattering angle and (b) to calculate the transmitted HAADF STEM intensity as a function of the relevant materials parameters and electron energy. The formalism can be also applied to determine TEM sample thicknesses by minimizing the contrast of the sample as a function of the electron energy.

Preclinical toxicologic studies of netilmicin.

1-N-Ethylsisomicin (netilmicin), a semisynthetic aminoglycoside antibiotic, was given parenterally to mice, rats, guinea pigs, rabbits, and dogs for toxicological evaluation. Acute signs of toxicity were consistent with neuromuscular blockade. Results of teratological studies in rats and rabbits were negative; the only effect observed was wavy ribs, a minor developmental variation, in rats. No effects were found on fertility, reproduction, or development of offspring. Single daily doses of 60 mg/kg s.c. for 10 weeks in young rats and 30 days in young dogs were non-toxic. No indication of toxicity was found in rats and dogs given single daily doses of 7.5 mg/kg i.v. for 2 weeks. Daily i.m. doses caused signs of neuromuscular blockade in rats after 2 weeks at 100 mg/kg and after 1 month at 50 mg/kg, and in dogs after 2 months at 75 mg/kg; dose levels of 150 mg/kg did not cause renal failure. No ocular changes or impairment of vestibular or auditory function were evident at any dose studied. Comparison with tobramycin, gentamicin, and kanamycin at s.c. doses of 50 or 150 mg/kg per day for 4 weeks showed netilmicin to be less nephrotoxic in rats than tobramycin or gentamicin and only slightly more nephrotoxic than kanamycin. Only mild changes were seen microscopically in kidneys of dogs given netilmicin at daily doses of 75 mg/kg i.m. for 3 months. The renal effects of netilmicin given at high multiples of the human therapeutic dose were one-half to one-third less that those of gentamicin and were not severe at any dosage.

Combining segmental systolic pressures and plethysmography to diagnose arterial occlusive disease of the legs.

Computer-assisted analysis of the data from SLP and PVR study of the legs with angiographically documented arterial occlusive disease, projected against a background of normal limbs, was used to assess the diagnostic value of each study, including its individual variables, as well as their varied combinations. The accuracy of both SLP and PVR interpretation was significantly improved by standarization against brachial values, but even with the aid of superimposed physician interpretation, each only reached 86 per cent when cases with multilevel occlusive disease were included. The combination of these two studies, which compensate for each other's limitations in several respects, achieved an overall accuracy of 97 per cent, with no errors observed in diagnosing either normal limbs or those with isolated occlusive disease. Objective diagnostic criteria for both SLP and PVR interpreatation are presented in algorithmic form.

Griseofulvin: a teratogenic study.

Griseofulvin, a fungistatic agent, was administered in oral doses of 125 to 1500 milligrams per kilogramn per day to pregnant rats during organogenesis. Evaluation of the offspring from dams treated with the largest doses, 63 and 75 times a therapeutic dose in man, indicated decreased survival rates and a syndrome of malformations.