Bone turnover biomarkers reflect radiation-induced bone injuries in women with non-metastatic rectal cancer.

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT-) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation.

Preoperative beta blockers and other drugs in relation to anastomotic leakage after anterior resection for rectal cancer.

AIM: Previous research has indicated that preoperative beta blocker therapy is associated with a decreased risk of complications after surgery for rectal cancer. This is thought to arise because of the anti-inflammatory activity of the drug. These results need to be reproduced and analyses extended to other drugs with such properties, as this information might be useful in clinical decision-making. The main aim of this work was to replicate previous findings of beta blocker use as a prognostic marker for postoperative leakage. We also investigated whether drug exposure might induce anastomotic leaks. METHOD: This is a retrospective multicentre cohort study, comprising 1126 patients who underwent anterior resection for rectal cancer between 2014 and 2018. The use of any preoperative beta blocker was treated as the primary exposure, while anastomotic leakage within 12 months of surgery was the outcome. Secondary exposures comprised angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins and metformin. Using multivariable regression, we performed a replication analysis with a predictive aim for beta blockers only, while adjustment for confounding was done in more causally oriented analyses for all drugs. We estimated incidence rate ratio (IRR) and relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Anastomotic leakage occurred in 20.6% of patients. Preoperative beta blockers were used by 22.7% of the cohort, while the leak distribution was almost identical between exposure groups. In the main replication analysis, no association could be detected (IRR 0.95, 95% CI 0.68-1.33). In the causally oriented analyses, only metformin affected the risk of leakage (RR 1.59, 95% Cl 1.31-1.92). CONCLUSION: While previous research has suggested that preoperative beta blocker use could be prognostic of anastomotic leakage, this study could not detect any such association. On the contrary, our results indicate that preoperative beta blocker use neither predicts nor causes anastomotic leakage after anterior resection for rectal cancer.

Anastomotic Leakage in Relation to Type of Mesorectal Excision and Defunctioning Stoma Use in Anterior Resection for Rectal Cancer.

BACKGROUND: Anastomotic leakage after anterior resection for rectal cancer is more common after total mesorectal excision compared to partial mesorectal excision but might be mitigated by a defunctioning stoma. OBJECTIVE: The aim is to assess how anastomotic leakage is affected by type of mesorectal excision and defunctioning stoma use. DESIGN: This is a retrospective multicenter cohort study evaluating anastomotic leakage after anterior resection. Multivariable Cox regression with HRs and 95% CIs was used to contrast mesorectal excision types and defunctioning stoma use with respect to anastomotic leakage, with adjustment for confounding. SETTINGS: This multicenter study included patients from 11 Swedish hospitals between 2014 and 2018. PATIENTS: Patients who underwent anterior resection for rectal cancer were included. MAIN OUTCOMES MEASURES: Anastomotic leakage rates within and after 30 days of surgery are described up to 1 year after surgery. RESULTS: Anastomotic leakage occurred in 24.2% and 9.0% of 1126 patients operated with total and partial mesorectal excision, respectively. Partial compared to total mesorectal excision was associated with a reduction in leakage, with an adjusted HR of 0.46 (95% CI, 0.29-0.74). Early leak rates within 30 days were 14.9% with and 12.5% without a stoma, whereas late leak rates after 30 days were 7.5% with and 1.9% without a stoma. After adjustment, defunctioning stoma was associated with a lower early leak rate (HR 0.47; 95% CI, 0.28-0.77). However, the late leak rate was nonsignificantly higher in patients with defunctioning stomas (HR 1.69; 95% CI, 0.59-4.85). LIMITATIONS: This study was limited by its retrospective observational study design. CONCLUSIONS: Anastomotic leakage is common up to 1 year after anterior resection for rectal cancer, where partial mesorectal excision is associated with a lower leak rate. Defunctioning stomas seem to decrease the occurrence of leakage, although partially by only delaying the diagnosis. See Video Abstract . FUGA ANASTOMTICA SEGN EL TIPO DE EXCISIN MESORRECTAL Y LA CONFECCIN DE OSTOMA DE PROTECCIN EN LA RESECCIN ANTERIOR POR CNCER DE RECTO: ANTECEDENTES:La fuga anastomótica después de una resección anterior por cáncer de recto es más frecuente después de la excisión total del mesorrecto comparada con la excisión parcial del mismo, pero podría mitigarse con la confección de ostomías de protección.OBJETIVO:El objetivo es evaluar cómo la fuga anastomótica se ve afectada según el tipo de excisión mesorrectal y la confección de una ostomía de protección.DISEÑO:Estudio de cohortes multicéntrico y retrospectivo que evalúa la fuga anastomótica después de la resección anterior. Se aplicó la regresión multivariada de Cox con los índices de riesgo (HR) y los intervalos de confianza (IC) al 95% para contrastar los tipos de excisión mesorrectal y el uso de otomías de protección con respecto a la fuga anastomótica, realizando ajustes respecto a las variables de confusión.AJUSTES:El presente estudio multicéntrico incluyó pacientes de 11 hospitales suecos entre 2014 y 2018.PACIENTES:Se incluyeron todos aquellos sometidos a resección anterior por cáncer de recto.PRINCIPALES MEDIDAS DE RESULTADOS:Las tasas de fuga anastomótica dentro y después de los 30 días de la cirugía fueron descritos hasta un año mas tarde al acto quirúrgico.RESULTADOS:La fuga anastomótica ocurrió en el 24,2% y el 9,0% de 1126 pacientes operados por excisión total y parcial del mesorrecto respectivamente.La excisión parcial del mesorrecto en comparación con la total se asoció con una reducción de la fuga, HR ajustado de 0,46 (IC del 95 %: 0,29 a 0,74). Las tasas de fuga temprana dentro de los 30 días fueron del 14,9 % con y el 12,5 % sin estoma, mientras que las tasas de fuga tardía después de 30 días fueron del 7,5 % con y el 1,9 % sin estoma.Después del ajuste de variables de confusión, las ostomías de protección se asociaron con una tasa de fuga temprana más baja (HR 0,47; IC 95 %: 0,28-0,77). Sin embargo, la tasa de fuga tardía no fue significativamente mayor en pacientes ostomizados (HR 1,69; IC 95%: 0,59-4,85).LIMITACIONES:Las limitaciones del presente estudio estuvieron vinculadas con el diseño de tipo observacional y retrospectivo.CONCLUSIONES:La fuga anastomótica es común hasta un año después de la resección anterior por cáncer de recto, donde la excisión parcial del mesorrecto se asocia con una menor tasa de fuga. La confección de ostomías de protección parece disminuir la aparición de fuga anastomótica, aunque en parte sólo retrasen el diagnóstico. (Traducción-Dr. Xavier Delgadillo ).

Splenic flexure mobilization and anastomotic leakage in anterior resection for rectal cancer: A multicentre cohort study.

BACKGROUND AND OBJECTIVE: Some colorectal surgeons advocate routine splenic flexure mobilization (SFM) when performing anterior resection for rectal cancer to ensure a tension-free anastomosis. Meta-analyses of smaller studies suggest that this approach does not influence anastomotic leakage rates, but larger multicentre studies are needed to confirm the safety of a selective strategy. The aim of this study is to evaluate the impact of SFM on anastomotic leakage. METHODS: This is a retrospective multicentre cohort study, comprising 1109 patients operated with anterior resection for rectal cancer in 2014-2018. Exposure was SFM, while anastomotic leakage within a year constituted the outcome. Stratified analyses were performed for type of mesorectal excision and surgical approach, as well as sensitivity analysis considering vascular tie placement. Multivariable Cox regression with hazard ratios (HRs) and 95% confidence intervals (CIs) was employed to adjust for confounding, while multiple imputation was used for missing data. RESULTS: SFM was performed in 381 patients (34.4%). Anastomotic leakage occurred in 83 (21.8%) and 123 (20.3%) patients operated with and without SFM, respectively. SFM was neither clearly detrimental nor beneficial regarding anastomotic leakage (adjusted HR = 0.82; 95% CI: 0.59-1.15), with no apparent differences for total or partial mesorectal excision and minimally invasive or open surgery. Concurrent high vascular ligation did not impact these results, and there was no evidence of interaction from centers with a more common use of SFM. CONCLUSIONS: SFM did not seem to influence the risk of anastomotic leakage after anterior resection for rectal cancer, regardless of type of mesorectal excision, use of minimally invasive surgery, or high vascular ligation.

The modified Glasgow Prognostic Score indicates an increased risk of anastomotic leakage after anterior resection for rectal cancer.

BACKGROUND: Preoperative inflammation might cause and also be a marker for anastomotic leakage after anterior resection for rectal cancer. Available biomarker indices such as the modified Glasgow Prognostic Score (mGPS) or the C-reactive protein-to-albumin ratio (CAR) may be clinically useful for leakage assessment. METHODS: Patients who underwent anterior resection for rectal cancer during 2014-2018 from a multicentre retrospective cohort were included. Data from the Swedish Colorectal Cancer registry and chart review at each hospital were collected. In a subset of patients, preoperative laboratory assessments were available, constituting the exposures mGPS and CAR. Anastomotic leakage within 12 months was the outcome. Causally oriented analyses were conducted with adjustment for confounding, as well as predictive models. RESULTS: A total of 418 patients were eligible for analysis. Most patients had mGPS = 0 (84.7%), while mGPS = 1 (10.8%) and mGPS = 2 (4.5%) were less common. mGPS = 2 (OR: 4.11; 95% CI: 1.69-10.03) seemed to confer anastomotic leakage, while this was not seen for mGPS = 1 (OR 1.09; 95% CI: 0.53-2.25). A cut off point of CAR > 0.36 might be indicative of leakage (OR 2.25; 95% CI: 1.21-4.19). Predictive modelling using mGPS rendered an area-under-the-curve of 0.73 (95% CI: 0.67-0.79) at most. DISCUSSION: Preoperative inflammation seems to be involved in the development of anastomotic leakage after anterior resection for cancer. Inclusion into prediction models did not result in accurate leakage prediction, but high degrees of systemic inflammation might still be important in clinical decision-making.

Impact of radiotherapy on bone health in women with rectal cancer - A prospective cohort study.

INTRODUCTION: Pelvic radiotherapy (RT) increases the risk of pelvic insufficiency fractures. The aim was to investigate if RT is associated with changes in serum bone biomarkers in women with rectal cancer, and to examine the incidence of radiation-induced bone injuries and the association with bone biomarkers. MATERIAL AND METHODS: Women diagnosed with rectal cancer stage I-III, planned for abdominal surgery ± preoperative (chemo) RT, were prospectively included and followed one year. Serum bone biomarkers comprised sclerostin (regulatory of bone formation), CTX (resorption), BALP and PINP (formation). A subgroup was investigated with annual pelvic magnetic resonance imaging (MRI). The association between RT and bone biomarkers was explored in regression models. RESULTS: Of 134 included women, 104 had surgery with preoperative RT. The formation markers BALP and PINP increased from baseline to one year in the RT-exposed group (p < 0.001, longitudinal comparison). In the adjusted regression analysis, the mean increase in PINP was higher in the RT-exposed than the unexposed group (17.6 (3.6-31.5) µg/L, p = 0.013). Sclerostin and CTX did not change within groups nor differed between groups. Radiation-induced injuries were detected in 16 (42%) of 38 women with available MRI. At one year, BALP was higher among women with than without bone injuries (p = 0.018, cross-sectional comparison). CONCLUSIONS: Preoperative RT was associated with an increase in the formation marker PINP, which could represent bone recovery following RT-induced injuries, commonly observed in participants evaluated with MRI. These findings should be further explored in larger prospective studies on bone health in rectal cancer patients.

Impact of Androgens on Sexual Function in Women With Rectal Cancer - A Prospective Cohort Study.

BACKGROUND: Women treated for rectal cancer are at risk of sexual dysfunction and impaired ovarian androgen production. AIM: To investigate a possible association between serum levels of endogenous androgens and sexual function in women with rectal cancer. METHODS: Women diagnosed with stage I-III rectal cancer were consecutively included and prospectively followed with the Female Sexual Function Index (FSFI) questionnaire from baseline to 2 years postoperatively and blood samples for hormone analyses, baseline to 1 year. Androgens were measured with liquid chromatography-mass spectrometry and electrochemiluminescence. The associations between the 4 measured androgens (testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulphate) and sexual function were assessed with generalized least squares random effects regression analysis in sexually active women. OUTCOMES: The primary outcome measure was the mean change observed in the FSFI total score when the serum androgen levels changed with one unit. Secondary outcomes were the corresponding mean changes in the FSFI domain scores: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain/discomfort. RESULTS: In the 99 participants, the median FSFI total score decreased from 21.9 (range 2.0 - 36.0) to 16.4 (3.5 - 34.5) and 11.5 (2.0 to 34.8) at 1 and 2-years follow-up. After adjustment for age, partner, psychological well-being, preoperative (chemo)radiotherapy, and surgery, total testosterone and androstenedione were significantly associated with FSFI total score (ß-coefficients 3.45 (95% CI 0.92 - 5.97) and 1.39 (0.46 - 2.33) respectively). Testosterone was significantly associated with the FSFI-domains lubrication and orgasm, free testosterone with lubrication, androstenedione with all domains except desire and satisfaction, and dehydroepiandrosterone sulphate with none of the domains. STRENGTHS AND LIMITATIONS: This is the first study investigating whether androgen levels are of importance for the impaired sexual function seen in women following rectal cancer treatment. The prospective design allows for repeated measures and the use of the FSFI for comparisons across studies. No laboratory data were collected at the 2-year follow-up, and the missing data could have further clarified the studied associations. CONCLUSION AND CLINICAL IMPLICATION: Testosterone and androstenedione were associated with sexual function in female rectal cancer patients. The results are of interest for future intervention studies and contribute to the understanding of sexual problems, which is an essential component of the rehabilitation process in pelvic cancer survivors. Svanström Röjvall A, Buchli C, Flöter Rådestad A, et al. Impact of Androgens on Sexual Function in Women With Rectal Cancer - A Prospective Cohort Study. J Sex Med 2021;18:1374-1382.

Best practice in major elective rectal/pelvic surgery: enhanced recovery after surgery (ERAS).

Within traditional clinical care, the postoperative recovery after pelvic/rectal surgery has been slow with high morbidity and long hospital stay. The enhanced recovery after surgery program is a multimodal approach to perioperative care designed to accelerate recovery and safely reduce hospital stay. This review will briefly summarize optimal perioperative care, before, during and after surgery in this group of patients and issues related to implementation and audit.

Analgesic effect of a single dose of betamethasone after ambulatory knee arthroscopy: a randomized controlled trial.

PURPOSE: Glucocorticoids are reported to improve postoperative analgesia. The purpose of the study was to investigate whether a preoperative, single dose of betamethasone could reduce pain after ambulatory arthroscopic knee surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial including patients scheduled for knee arthroscopy. The intervention was an intravenous injection of betamethasone 8 mg or placebo. The primary outcome was pain day 1 evaluated by a verbal descriptor scale (VDS). RESULTS: In total, 74 patients (betamethasone = 34; placebo = 40) were randomized. One patient in each group was excluded from analysis. During activity day 1 following surgery, the proportion with no or minor pain was significantly (p = 0.030) higher in the betamethasone group (22 of 33; 67 %) compared with the placebo group (17 of 39; 44 %). At rest, the corresponding figures were 26 of 33 (79 %) for betamethasone and 24 of 39 (62 %) for placebo (p = 0.062). After 3 months of follow-up, no patient receiving betamethasone experienced adverse events while six receiving placebo did (postoperative nausea and vomiting in five and delayed wound healing in one). CONCLUSIONS: An analgesic benefit was seen day 1 following surgery. This indicates that betamethasone has a place in ambulatory arthroscopic knee surgery. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ (identifier 2009-014717-27).

Increased risk of colorectal cancer in patients diagnosed with breast cancer in women.

BACKGROUND: Epidemiological studies have shown a potential association between sex hormones and colorectal cancer. The risk of colorectal cancer in breast cancer patients who may have been exposed to increased levels of endogenous sex hormones and/or exogenous sex hormones (e.g. anti-hormonal therapy) has not been thoroughly evaluated. METHODS: Using the National Swedish Cancer Register we established a population-based prospective cohort of breast cancer patients in women diagnosed in Sweden between 1961 and 2010. Subsequent colorectal cancers were identified from the same register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs) were used to estimate the risk of colorectal cancer after a diagnosis of breast cancer. The association between breast cancer therapy and risk of colorectal cancer was evaluated in a subcohort of breast cancer patients treated in Stockholm between 1977 and 2007. Hazard ratios (HRs) and 95%CIs were estimated using Cox regression models. RESULTS: In a cohort of 179,733 breast cancer patients in Sweden, 2571 incident cases of colorectal cancer (1008 adenocarcinomas in the proximal colon, 590 in the distal colon and 808 in the rectum) were identified during an average follow-up of 9.68 years. An increased risk of colorectal adenocarcinoma was observed in the breast cancer cohort compared with that in the general population (SIR=1.59, 95%CI: 1.53, 1.65). Adenocarcinoma in the proximal colon showed a non-significantly higher SIR (1.72, 95%CI: 1.61, 1.82) compared with the distal colon (1.46, 95%CI: 1.34, 1.58). In the subcohort of 20,171 breast cancers with available treatment data, 299 cases with colorectal cancers were identified. No treatment-dependent risk of colorectal cancer was observed among the breast cancer patients. CONCLUSION: An increased risk of colorectal adenocarcinoma - especially in the proximal colon - was observed in the breast cancer cohort. Breast cancer treatment did not alter this risk.

Evidence or eminence in abdominal surgery: recent improvements in perioperative care.

Repeated surveys from Europe, the United States, Australia, and New Zealand have shown that adherence to an evidence-based perioperative care protocol, such as Enhanced Recovery After Surgery (ERAS), has been generally low. It is of great importance to support the implementation of the ERAS protocol as it has been shown to improve outcomes after a number of surgical procedures, including major abdominal surgery. However, despite an increasing awareness of the importance of structured perioperative management, the implementation of this complex protocol has been slow. Barriers to implementation involve both patient- and staff-related factors as well as practice-related issues and resources. To support efficient and successful implementation, further educational and structural measures have to be made on a national or regional level to improve the standard of general health care. Besides postoperative morbidity, biological and physiological variables have been quite commonly reported in previous ERAS studies. Little information, however, has been obtained on cost-effectiveness, long-term outcomes, quality of life and patient-related outcomes, and these issues remain important areas of research for future studies.

Can nutritional supplements and rectal enema be used as bowel cleansing for colonoscopy?--Results of a randomized controlled pilot study.

OBJECTIVE: Currently available preparations for colonoscopy have low tolerability and may cause fluid and electrolyte shifts. An alternative method of bowel cleansing is required. MATERIAL AND METHODS: Preparation of the gut using oral nutritional supplements (ONS) and rectal enema was tested as an alternative method of bowel cleansing. During 2008-2012, patients were randomized to oral nutritional supplements (n = 27) for 5 days and rectal enema or polyethylene glycol (PEG) (n = 23) prior to colonoscopy. Blinded endoscopists rated the degree of bowel cleansing according to the Ottawa bowel preparation scale (OBS) (primary outcome). Tolerability of either preparation was also assessed RESULTS: Due to a high rate of bowel cleansing failure among patients receiving ONS, the study was interrupted prematurely. Colonoscopies were incomplete due to stools in 6 of 27 patients in the ONS group compared to 1 of 23 in the PEG group (ns). The mean total OBS were 8.3 ± 3.3 and 5.3 ± 2.8, respectively (p = 0.002). Four patients (15%) in the ONS group and eight patients (35%) receiving PEG had an OBS score ≤4 (good preparation) (ns). ONS was better tolerated than PEG with more patients reporting acceptable taste (27 of 27 [100%] vs. 15 of 23 [65%], p = 0.001), and fewer reporting difficulties with the intake (0 of 27 [0%] vs. 10 of 23 [43%], p < 0.001) and nausea (5 of 27 [19%] vs. 13 of 23 [57%], p < 0.008). CONCLUSIONS: For routine use, ONS with enema instead of traditional preparation for colonoscopy with PEG cannot be generally recommended.