High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer.

In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERß) is considered the dominant subtype. However, in colon carcinomas, the ERα/ß ratio is often increased, an observation that prompted us to further investigate ERα's role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibited positive ERα nuclear expression, which was significantly higher in cancer tissues than in matched normal tissues. Importantly, patients with positive nuclear ERα expression had a poor prognosis. Furthermore, positive ERα expression correlated with increased levels of the G-protein coupled cysteinyl leukotriene receptor 1 (CysLT1R) and nuclear ß-catenin, both known tumour promoters. In mouse models, ERα expression was decreased in Cysltr1-/- CAC (colitis-associated colon cancer) mice but increased in ApcMin/+ mice with wild-type Cysltr1. In cell experiments, an ERα-specific agonist (PPT) increased cell survival via WNT/ß-catenin signalling. ERα activation also promoted metastasis in a zebrafish xenograft model by affecting the tight junction proteins ZO-1 and Occludin. Pharmacological blockade or siRNA silencing of ERα limited cell survival and metastasis while restoring tight junction protein expression. In conclusion, these findings highlight the potential of ERα as a prognostic marker for CRC and its role in metastasis.

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 ).

Minor impact of anastomotic leakage in anterior resection for rectal cancer on long-term male urinary and sexual function.

PURPOSE: Anastomotic leakage after anterior resection for rectal cancer induces bowel dysfunction, but the influence on urinary and sexual function is largely unknown. This cross-sectional cohort study evaluated long-term effect of anastomotic leakage on urinary and sexual function in male patients. METHODS: Patients operated with anterior resection for rectal cancer in 15 Swedish hospitals 2007-2013 were identified. Anastomotic leakage and other clinical variables were retrieved from the Swedish Colorectal Cancer Registry and medical records. Urinary and sexual dysfunction were evaluated at 4 to 11 years after surgery using the International Prostate Symptom Score, International Index of Erectile Function, and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire CR29. The effect of anastomotic leakage on average scores of urinary and sexual dysfunction was evaluated as a primary outcome, and the single items permanent urinary catheter and sexual inactivity as secondary outcomes. The association of anastomotic leakage and functional outcomes was analyzed using regression models with adjustment for confounders. RESULTS: After a median follow-up of 84 months (interquartile range: 67-110), 379 out of 864 eligible men were included. Fifty-nine (16%) patients had anastomotic leakage. Urinary incontinence was more common in the leakage group, with an adjusted mean score difference measured by EORTC QLQ ColoRectal-29 of 8.69 (95% confidence interval: 0.72-16.67). The higher risks of urinary frequency, permanent urinary catheter, and sexual inactivity did not reach significance. CONCLUSION: Anastomotic leakage after anterior resection had a minor negative impact on urinary and sexual function in men.

Postoperative morbidity following Hartmann's procedure in comparison to anterior resection and abdominoperineal resection for rectal cancer-a population-based study.

AIM: There is ongoing controversy regarding the extent to which Hartmann's procedure (HP) should be used in rectal cancer treatment. This study was designed to investigate 30-day postoperative morbidity and mortality following HP, anterior resection (AR) and abdominoperineal resection (APR) for rectal cancer using a national registry. METHODS: All patients operated for rectal cancer, tumour height 5-15 cm, between the years 2010 and 2017, were identified through the Swedish colorectal cancer registry. RESULTS: A total of 8476 patients were included: 1210 (14%) undergoing HP, 5406 (64%) AR and 1860 (22%) APR. HP was associated with an increased risk of intra-abdominal infection (OR 1.7, CI 1.26-2.28, P = 0.0004) compared to AR and APR, while APR was related to an increased risk of overall complications (OR 1.18, CI 1.01-1.40, P = 0.040). No significant difference was observed in the rate of reoperations and readmissions between HP, AR and APR, and type of surgical procedure was not a risk factor for 30-day mortality. Findings from a subgroup analysis of patients with a tumour 5-7 cm from the anal verge revealed that HP was not associated with increased risk for complications or 30-day mortality. CONCLUSIONS: For patients where AR is not appropriate HP is a valid alternative with a favourable outcome. APR was associated with the highest overall 30-day complication rate.

Postoperative complications and emergency surgeries in colorectal cancer patients <50 years-a national cohort study.

AIM: The incidence of colorectal cancer (CRC) in Sweden is increasing in individuals <50 years. This study aimed to examine differences in postoperative 30-day complications and rate of emergency surgeries in CRC patients <50 years at diagnosis compared to older age groups since population-based research on this topic is scarce. METHOD: This population-based study included data from the Swedish Colorectal Cancer Registry for patients undergoing CRC resection between 2010 and 2018. Bivariate analysis and logistic regression were used to analyse the relationship between age groups (<50, 50-79 and ≥80 years) and probability of postoperative 30-day complications adjusted for gender, tumour localization, neoadjuvant (chemo)radiotherapy and American Society of Anesthesiologists score. RESULTS: In total 33 320 patients were included. Patients <50 years had a lower American Society of Anesthesiologists score, more advanced tumours and received more neoadjuvant treatment. Emergency surgeries were less common in the youngest age group (P < 0.001) as well as overall postoperative 30-day complications: ORadj 0.84 (95% CI 0.74-0.96) compared to those ≥80 years. Surgical complications were more common in age groups <50 and 50-79 years (16.5% and 16.9% respectively) compared to patients ≥80 years (14.1%) (P < 0.001). Anastomotic leakage and intra-abdominal infections were more frequent in patients <50 years (5.7% and 3.5% respectively) compared to age groups 50-79 years (5.1% and 2.8% respectively) and ≥80 years (3.5% and 2.1% respectively) (P < 0.001). Wound infections were more common in the two youngest age groups compared to patients ≥80 years (5.3% vs. 3.7% respectively) (P < 0.001). CONCLUSION: Colorectal cancer patients <50 years and 50-79 years had a higher proportion of surgical complications regarding anastomotic leakage, intra-abdominal infections and wound infections but lower overall postoperative complications. The incidence of surgical emergencies was highest amongst patients ≥80 years. Postoperative diagnostic workup in symptomatic individuals <50 years is warranted.

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.

Hartmann's procedure in rectal cancer surgery is often an intraoperative decision: a retrospective multicenter study.

PURPOSE: This study aimed to investigate patient-related factors predicting the selection of rectal cancer patients to Hartmann's procedure as well as to investigate how often, and on what grounds, anterior resection is intraoperatively changed to Hartmann's procedure. METHODS: Prospectively collected data from the Swedish Colorectal Cancer Registry regarding patients with rectal cancer operated upon from January 1 2007 to June 30 2017 in the county of Skåne were retrospectively reviewed. Data were expanded with further details from medical charts. A univariable analysis was performed to investigate variables associated with unplanned HP and significant variables included in a multivariable logistic regression analysis. RESULTS: Altogether, 1141 patients who underwent Hartmann's procedure (275 patients, 24%), anterior resection (491 patients, 43%), or abdominoperineal resection (375 patients, 33%) were included. Patients undergoing Hartmann's procedure were significantly older and had more frequently comorbidity. The decision to perform Hartmann's procedure was made preoperatively in 209 (76%) patients, most commonly because of a comorbidity (27%) or oncological reasons (25%). Patient preference was noted in 8% of cases. In 64 cases (23%), the decision was made intraoperatively, most often due to anastomotic difficulties (60%) and oncological reasons (22%). Anastomotic difficulties were most often reported due to technical difficulties, a low tumor or neoadjuvant radiotherapy. Male gender was a significant risk factor for undergoing unplanned Hartmann's procedure. CONCLUSIONS: The decision to perform Hartmann's procedure was frequently made intraoperatively. Hartmann's procedure should be considered and discussed preoperatively in old and frail patients, especially in the presence of mid-rectal cancer and/or male gender, since these factors increase the risk of intraoperative anastomotic difficulties.

Family members' conceptions of their supportive care needs across the colorectal cancer trajectory - A phenomenographic study.

AIM: To describe the variations of family members' conceptions of their supportive care needs (SCN) across the colorectal cancer (CRC) trajectory. DESIGN: A descriptive qualitative study with a phenomenographic approach. METHOD: Individual semi-structured interviews were conducted from May 2022 to October 2022 with 23 family members of persons diagnosed with colorectal cancer. The interviews were analysed using phenomenographic analysis following the Consolidated criteria for reporting qualitative research (COREQ) checklist. RESULTS: The phenomenographic analysis resulted in five categories. Not of importance describes family members' needs as unimportant due to the good prognosis and the organization of care and in relation to the needs of others. Only satisfiable by professionals describes information possessed by the healthcare professionals as key, as well as the need for professional counselling for the family members to process their emotions. Managed by themselves describes family members preferring to manage their SCN themselves by turning to the appropriate social support and/or by using coping skills. Understood retrospectively describes SCN as only understandable when things have calmed down and as requiring one's own experience to understand. Left unmet describes SCN as unnoticed by the healthcare professionals or not brought to light by the family members, or family members not knowing where to turn for support. CONCLUSION: Supportive care should involve individualized information, proactive and repeated assessments of needs across the trajectory, as well as encouragement of family members to reflect on their needs and to accept support when needed. IMPACT: There is a gap in the literature regarding family members' SCN across the CRC trajectory which this study addresses. Findings show five categories of family members' conceptions of their SCN. Those findings could serve as a basis for the development of clinical colorectal supportive care across the cancer trajectory. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Findings show that to offer family members of persons diagnosed with colorectal cancer support only at the time of diagnosis is insufficient. Instead, the healthcare team is recommended to proactively and repeatedly try to identify those in need and the characteristics of their needs. In addition, it is important to offer individualized information and strive to encourage family members to reflect on their situation and to not suppress their own needs if emerging. REPORTING METHOD: Reporting adheres to the consolidated criteria for reporting qualitative research (COREQ) checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Circumferential Resection Margin is Associated With Distant Metastasis After Rectal Cancer Surgery: A Nation-wide Population-based Study Cohort.

OBJECTIVE: To evaluate circumferential resection margin (CRM) as a risk factor for distant metastasis (DM) in rectal cancer. SUMMARY OF BACKGROUND DATA: The treatment of rectal cancer has evolved over the last decades. Surgical radicality is considered the most important factor in preventing recurrences including local and distant. CRM ≤1.0 mm is considered to increase recurrence risk. This study explores the risk of DM in relation to exact CRM. METHODS: All patients treated with abdominal resection surgery for rectal cancer between 2005 and 2013 in Sweden were eligible for inclusion in this retrospective study. Primary endpoint was DM. RESULTS: Twelve thousand one hundred forty-six cases were identified. Eight thousand five hundred ninety-three cases were analyzed after exclusion. Seven hundred seventeen (8.6%) patients had CRM ≤1.0mm and 7577 (91.4%) patients had CRM >1.0 mm. DM recurrence rate at 5 years was 42.1% (95% CI 32.5-50.3), 31.5% (95% CI 27.3-35.5), 25.8% (95% Confidence Interval (CI) 16.2-34.4), and 19.5% (95% CI 18.5-19.5) when CRM was 0.0 mm, 0.1 to 1.0 mm, 1.1 to 1.9 mm, and CRM ≥2mm, respectively. Multivariable analysis revealed higher DM risk in CRM 0.0-1.0 mm versus >1.0 mm (hazard ratio 1.30, 95% CI 1.05-1.60; P = 0.015). No significant difference in DM risk in CRM 1.1-1.9 mm versus ≥2.0 mm (hazard ratio 0.66, 95% CI 0.34-1.28; P = 0.224) could be detected. CONCLUSIONS: The risk of DM decreases with increasing CRM. Moreover, CRM ≤1.0 mm is a significant risk factor for DM. Thus, CRM is a dominant factor when discussing risk of DM after rectal cancer surgery.

Negative Prognostic Impact of Tumor Deposits in Rectal Cancer: A National Study Cohort.

OBJECTIVE: To investigate whether tumor deposits (TDs) in rectal cancer are associated with increased recurrence risk and decreased survival. BACKGROUND: Tumor deposits (TDs) are considered a risk factor for recurrence after colon cancer resection, and the presence of TDs prompts adjuvant chemotherapy. The prognostic relevance of TDs in rectal cancer requires further exploration. METHODS: All patients treated with abdominal resection surgery for rectal cancer in Sweden between 2011 and 2014 were eligible for inclusion in this retrospective cohort study based on prospectively collected data from the Swedish Colorectal Cancer Registry. The primary endpoint was local recurrence or distant metastasis. Secondary outcomes were overall and relative survival. RESULTS: Five thousand four hundred fifty-five patients were identified of which 3769 patients were analyzed after exclusion. TDs were found in 404 (10.7%) patients, including 140 (3.7%) patients with N1c-status. In TD-positive patients, local recurrence and distant metastasis rates at 5 years were 6.3% [95% CI 3.8-8.8%] and 38.9% [95% CI, 33.6-43.5%] compared with 2.7% [95% CI, 2.1-3.3%] and 14.3% [95% CI, 13.1-15.5%] in TD-negative patients. In multivariable regression analysis, the risk of local recurrence and distant metastasis were increased; HR 1.86 [95% CI, 1.09-3.19; P =0.024] and 1.87 [95% CI, 1.52-2.31; P =<0.001], respectively. Overall survival at 5 years was 68.8% [95% CI, 64.4-73.4%] in TD-positive patients and 80.7% [95% CI, 79.4-82.1%] in TD-negative patients. pN1c-patients had similar outcomes regarding local recurrence, distant metastasis, and survival as pN1a-b stage patients. TD-positive pN1a-b patients had significantly worse outcomes whereas TDs did not affect outcomes in pN2a-b patients. CONCLUSION: This study suggests that TDs have a negative impact on the prognosis in rectal cancer. Thus, efforts should be made to diagnose TD-positive rectal cancer patients preoperatively.

Impact of previous diverticulitis on 5-year survival and recurrence rates in patients with colorectal cancer.

BACKGROUND: Diverticulitis and colorectal cancer (CRC) share epidemiological characteristics, but their relationship remains unknown. It is unclear if prognosis following CRC differ for patients with previous diverticulitis compared to those with sporadic cases and patients with inflammatory bowel disease or hereditary syndromes. AIM: The aim was to determine 5-year survival and recurrence after colorectal cancer in patients with previous diverticulitis, inflammatory bowel disease and hereditary colorectal cancer compared to sporadic cases. METHODS: Patients <75 years of age diagnosed with colorectal cancer at Skåne University Hospital Malmö, Sweden, between January 1st 2012 and December 31st 2017 were identified through the Swedish colorectal cancer registry. Data was retrieved from the Swedish colorectal cancer registry and chart review. Five-year survival and recurrence in colorectal cancer patients with previous diverticulitis were compared to sporadic cases, inflammatory bowel disease associated and hereditary colorectal cancer. RESULTS: The study cohort comprised 1052 patients, 28 (2.7%) with previous diverticulitis, 26 (2.5%) IBD, 4 (1.3%) hereditary syndromes and 984 (93.5%) sporadic cases. Patients with a history of acute complicated diverticulitis had a significantly lower 5-year survival rate (61.1%) and higher recurrence rate (38.9%) compared to sporadic cases (87.5% and 18.8% respectively). CONCLUSION: Patients with acute complicated diverticulitis had worse 5-year prognosis compared to sporadic cases. The results emphasize the importance of early detection of colorectal cancer in patients with acute complicated diverticulitis.

Adverse impact of tumor deposits in lymph node negative rectal cancer - a national cohort study.

PURPOSE: This study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer. METHODS: Patients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node-negative rectal cancer. RESULTS: A total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72-6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35-2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86-4.11, p = 0.11]. CONCLUSION: TDs are a negative predictor of DM and OS in lymph node-negative rectal cancer and could be taken into consideration when planning adjuvant treatment.

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.

The impact of the anastomotic configuration on low anterior resection syndrome 3 years after total mesorectal excision for rectal cancer: a national cohort study.

AIM: After low anterior resection, the bowel can be anastomosed in different ways. It is not clear which configuration is optimal from a functional and complication point of view. The primary aim was to investigate the impact of the anastomotic configuration on bowel function evaluated by the low anterior resection syndrome (LARS) score. Secondarily, the impact on postoperative complications was evaluated. METHOD: All patients who had undergone low anterior resection from 2015 to 2017 were identified in the Swedish Colorectal Cancer Registry. Three years after surgery, patients were sent an extensive questionnaire and were analysed based on anastomotic configuration ('J-pouch/side-to-end anastomosis' or 'straight anastomosis'). Inverse probability weighting by propensity score was used to adjust for confounding factors. RESULTS: Among 892 patients, 574 (64%) responded, of whom 494 patients were analysed. After weighting, the anastomotic configuration had no significant impact on the LARS score (J-pouch/side-to-end OR 1.05, 95% confidence interval [CI] 0.82-1.34). The J-pouch/side-to-end anastomosis was significantly associated with overall postoperative complications (OR 1.43, 95% CI 1.06-1.95). No significant difference was seen regarding surgical complications (OR 1.14, 95% CI 0.78-1.66). CONCLUSION: This is the first study investigating the impact of the anastomotic configuration on long-term bowel function, evaluated by the LARS score, in an unselected national cohort. Our results suggested no benefit for J-pouch/side-to-end anastomosis on long-term bowel function and postoperative complication rates. The anastomotic strategy may be based upon the anatomical conditions of the patient and surgical preference.

Defunctioning stoma in anterior resection for rectal cancer does not impact anastomotic leakage: a national population-based cohort study.

BACKGROUND: Anterior resection (AR) is considered the gold standard for curative cancer treatment in the middle and upper rectum. The goal of the sphincter-preserving procedure, such as AR, is vulnerable to anastomotic leak (AL) complications. Defunctioning stoma (DS) became the protective measure against AL. Often a defunctioning loop-ileostomy is used, which is associated with substantial morbidity. However, not much is known if the routine use of DS reduces the overall incidence of AL. METHODS: Elective patients subjected to AR in 2007-2009 and 2016-18 were recruited from the Swedish colorectal cancer registry (SCRCR). Patient characteristics, including DS status and occurrence of AL, were analyzed. In addition, independent risk factors for AL were investigated by multivariable regression. RESULTS: The statistical increase of DS from 71.6% in 2007-2009 to 76.7% in 2016-2018 did not impact the incidence of AL (9.2% and 8.2%), respectively. DLI was constructed in more than 35% of high-located tumors ≥ 11 cm from the anal verge. Multivariable analysis showed that male gender, ASA 3-4, BMI > 30 kg/m2, and neoadjuvant therapy were independent risk factors for AL. CONCLUSION: Routine DS did not decrease overall AL after AR. A selective decision algorithm for DS construction is needed to protect from AL and mitigate DS morbidities.

High Risk of Low Anterior Resection Syndrome in Long-term Follow-up After Anastomotic Leakage in Anterior Resection for Rectal Cancer.

BACKGROUND: Low anterior resection syndrome is common after sphincter-sparing surgery, but it is unclear to what extent anastomotic leakage after anterior resection contributes to this condition. OBJECTIVE: The aim of this study is to assess the long-term effect of anastomotic leakage on the occurrence of major low anterior resection syndrome. DESIGN: This is a retrospective observational cohort study evaluating low anterior resection syndrome 4 to 11 years after index surgery. After propensity score-matching using the covariates sex, age, tumor stage, comorbidity, neoadjuvant treatment, extent of mesorectal excision, and defunctioning stoma at index surgery, the effect of anastomotic leakage on low anterior resection syndrome was investigated using relative risk and 95% CI. SETTINGS: This multicenter study included patients from 15 Swedish hospitals between 2007 and 2013. PATIENTS: Patients who underwent anterior resection for rectal cancer were included. MAIN OUTCOME MEASURES: Outcome measures included patient-reported major low anterior resection syndrome, obtained via a postal questionnaire that included a question on stoma status. RESULTS: Among 1099 patients, 653 (59.4%) responded in at a median of 83.5 (interquartile range 66 to 110) months postoperatively. After excluding patients with residual stoma or incomplete responses, 544 remained; of these, 42 had anastomotic leakage. Patients with anastomotic leakage were more likely to have major low anterior resection syndrome (66.7% [28/42]) than patients without leakage (45.8% [230/502]). After matching, anastomotic leakage was significantly related to major low anterior resection syndrome (relative risk 2.3; 95% CI 1.4-3.9) and the individual symptom of urgency (relative risk 2.1; 95% CI 1.1-4.1). LIMITATIONS: This study was limited by its retrospective observational study design. CONCLUSIONS: In long-term follow-up, major low anterior resection syndrome is common after anterior resection for rectal cancer. Anastomotic leakage appears to increase the risk of major low anterior resection syndrome, with urgency as a major contributing symptom. See Video Abstract at http://links.lww.com/DCR/B868 . ALTO RIESGO DE SNDROME DE RESECCIN ANTERIOR BAJA EN EL SEGUIMIENTO A LARGO PLAZO TRAS FUGA ANASTOMTICA EN RESECCIN ANTERIOR POR CNCER DE RECTO: ANTECEDENTES:El síndrome de resección anterior baja es común después de una cirugía con preservación de esfínter pero no está claro hasta qué punto contribuye a esta condición la fuga anastomótica después de una resección anterior.OBJETIVO:El objetivo de este estudio es evaluar el efecto a largo plazo de la fuga anastomótica sobre la aparición de un síndrome de resección anterior baja mayor.DISEÑO:Se trata de un estudio de cohorte observacional retrospectivo que evalúa el síndrome de resección anterior baja 4-11 años después de la cirugía índice. Después del apareamiento por puntuación de propensión utilizando las covariables sexo, edad, estadio del tumor, comorbilidad, tratamiento neoadyuvante, extensión de la escisión mesorrectal y estoma de derivación en la cirugía índice, se investigó el efecto de la fuga anastomótica en el síndrome de resección anterior baja utilizando el riesgo relativo y intervalos de confianza de 95%.AJUSTES:Este estudio multicéntrico incluyó pacientes de 15 hospitales suecos entre 2007 y 2013.PACIENTES:Se incluyeron pacientes que fueron sometidos a resección anterior por cáncer de recto.PRINCIPALES MEDIDAS DE DESENLACE:Síndrome de resección anterior baja mayor informado por el paciente, obtenido a través de un cuestionario postal que incluye una pregunta sobre el estado de estomas.RESULTADOS:De 1099 pacientes, 653 (59,4%) respondieron una mediana de 83,5 meses después de la operación (rango intercuartílico 66-110).Después de excluir a los pacientes con estoma residual o respuestas incompletas, quedaron 544; de estos, 42 tuvieron fuga anastomótica. Los pacientes con fuga anastomótica tenían síndrome de resección anterior baja mayor en el 66,7% (28/42) en comparación con el 45,8% (230/502) de los pacientes sin fuga. Después del apareamiento, la fuga anastomótica se relacionó significativamente con el síndrome de resección anterior baja mayor (riesgo relativo 2,3; intervalo de confianza del 95%: 1,4-3,9) y con el síntoma individual de urgencia (riesgo relativo 2,1; intervalo de confianza del 95% 1,1-4,1).LIMITACIONES:Este estudio estuvo limitado por su diseño de estudio observacional retrospectivo.CONCLUSIONES:En el seguimiento a largo plazo, el síndrome de resección anterior baja mayor es común después de la resección anterior por cáncer de recto. La fuga anastomótica parece aumentar el riesgo de síndrome de resección anterior baja mayor, siendo la urgencia uno de los principales síntomas contribuyentes. Consulte Video Resumen en http://links.lww.com/DCR/B868 . (Traducción-Dr. Juan Carlos Reyes ).

Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results.

BACKGROUND: Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). METHODS: The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. RESULTS: The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. CONCLUSIONS: This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.

Perineal wound healing after abdominoperineal resection for rectal cancer: a retrospective cohort study.

PURPOSE: Delayed perineal wound healing is a common complication after abdominoperineal resection (APR) in rectal cancer. The primary aim of this study was to evaluate the number of patients with delayed wound healing after APR. Secondary aims were to identify risk factors, and describe treatment. METHODS: Prospectively collected data from the Swedish Colorectal Cancer Registry (SCRCR) was used for retrospective analysis of APR performed at Skåne University Hospital Malmö between 2013 and 2018. Medical charts were retrospectively reviewed. Delayed healing was defined as non-healed perineal wound 30 days postoperatively. Patients undergoing extralevator APR requiring reconstruction were excluded. Statistical analysis was made using SPSS. Risk factors for impaired wound healing were analyzed using a multivariable model. RESULTS: A total of 162 patients were included, of which 114 underwent standard APR (sAPR) and 48 patients intersphincteric APR (isAPR). In the total population, 69% (111/162) were male, with median age 71 (26-87). The overall healing rate was 52% (85/162); 44% (50/114) in sAPR vs 73% (35/48) in isAPR (P < 0.001). Risk factors for impaired healing after multivariable analysis were BMI > 30 (OR 7.0; CI 95% 1.8-26.2, P = 0.004), reoperation (OR 7.9; CI 95% 1.6-39.8, P = 0.013), neoadjuvant radiotherapy (OR 5.2; CI 95% 1.02-25.1, P = 0.047) and sAPR (OR 2.598; CI 95% 1.05-6.41, P = 0.038). Eight percent (13/162) required an intervention (Clavien-Dindo ≥ 3). CONCLUSION: Delayed perineal wound healing is a frequent complication after APR but the majority could be treated conservatively. Several risk factors were identified. Further studies aiming at interventions reducing delayed perineal wound healing after APR are warranted.

Low incidence of pelvic sepsis following Hartmann's procedure for rectal cancer: a retrospective multicentre study.

BACKGROUND: Results of previous studies regarding pelvic sepsis after Hartmann's procedure (HP) for rectal cancer have been inconsistent and few studies report the risk factors. This study aimed to investigate the incidence of pelvic sepsis after HP, identify risk factors and describe when as well as how pelvic sepsis was diagnosed and treated. METHODS: Data were collected from the Swedish Colorectal Cancer Registry on all patients undergoing HP for rectal cancer in the county of Skåne from 2007-2017. Patients diagnosed with pelvic sepsis were compared with patients without pelvic sepsis and risk factors for developing pelvic sepsis were analysed in a multivariable model. RESULTS: A total of 252 patients were included in the study, with 149 (59%) males, and a median age of 75 years (range 20-92). Altogether, 27 patients (11%) were diagnosed with pelvic sepsis. Risk factors for developing pelvic sepsis were neoadjuvant radiotherapy (OR 7.96, 95% CI 2.54-35.36) and BMI over 25 kg/m2 (OR 5.26, 95% CI 1.80-19.50). Median time from operation to diagnosis was 21 days (range 5-355) with 11 (40%) patients diagnosed beyond 30 days postoperatively. The majority of cases 19 (70%) were treated conservatively and none needed major surgery. CONCLUSION: Pelvic sepsis occurred in 11% of patients. Neoadjuvant radiotherapy and higher BMI were significant risk factors for developing pelvic sepsis. Forty percent of patients were diagnosed later than 30 days postoperatively and most patients were successfully treated conservatively. Our findings suggest that HP is a valid treatment option for rectal cancer when anastomosis is inappropriate, even in patients receiving neoadjuvant radiotherapy.

Management of acute uncomplicated diverticulitis without antibiotics: compliance and outcomes -a retrospective cohort study.

METHODS: Recent randomized control trials (RCTs) have confirmed that antibiotics in acute uncomplicated diverticulitis (AUD) neither accelerate recovery nor prevent complications or recurrences. A retrospective cohort study was conducted, including all consecutive AUD patients hospitalized 2015- 2018 at Helsingborg Hospital (HH) and Skåne University Hospital (SUS), Sweden. HH had implemented a non-antibiotic treatment protocol in 2014 while SUS had not. Main outcomes were proportion of patients treated with antibiotics, complications, recurrences, and adherence to routinely colon evaluation. RESULTS: A total of 583 AUD patients were enrolled, 388 at SUS and 195 at HH. The diagnosis was CT-verified in 320 (83%) vs. 186 (95%) patients respectively (p < 0.001). Forty-three (11%) and 94 (48%) of patients respectively did not receive antibiotics during hospitalization (p < 0.001). CRP was higher in the antibiotic group compared to the non-antibiotic group, both at admission and peak (90 mg/L vs 65 mg/L; p = 0.016) and (138 mg/L and 97 mg/L; p < 0.001). There were no significant differences in recurrences (22.0% vs. 22.6%; p = 0.87) and complications (2.5% vs. 2.9%; p = 0.77) between the antibiotic/non-antibiotic groups. CONCLUSION: The structured treatment protocol led to reduced antibiotic use and a higher standard of care in terms of CT-verification. Clinicians' compliance to the treatment protocol and best clinical practice was poor and warrants further studies.