Current Management of T1 Colon Cancer in Denmark: A Nationwide Cohort Study.

OBJECTIVE: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry. BACKGROUND: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge. METHODS: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival. RESULTS: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis. CONCLUSIONS: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed.

Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study.

AIM: Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. METHOD: This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. RESULTS: A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. CONCLUSION: LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Associations between health-related quality of life and subsequent need for specialized palliative care and hospital utilization in patients with gastrointestinal cancer-a prospective single-center cohort study.

BACKGROUND: We lack knowledge of which factors are associated with the risk of developing complex palliative care needs. The aim of this study was to investigate the associations between patient-reported health-related quality of life and subsequent referral to specialized palliative care (SPC) and hospital utilization. METHODS: This was a prospective single-center cohort study. Data on patient-reported outcomes were collected through the European Organization of Research and Treatment of Cancer Questionnaire-Core-15-Palliative Care (EORTC QLQ-C15-PAL) at the time of diagnosis. Covariates and hospital utilization outcomes were collected from medical records. Adjusted logistic and Poisson regression were applied in the analyses. Participants were newly diagnosed with incurable gastrointestinal cancer and affiliated with a palliative care case management intervention established in a gastroenterology department. RESULTS: Out of 397 patients with incurable gastrointestinal cancer, 170 were included in the study. Patients newly diagnosed with incurable gastrointestinal cancer experienced a substantial burden of symptoms. Pain was significantly associated with subsequent referral to SPC (OR 1.015; 95% CI 1.001-1.029). Patients with lower education levels (OR 0.210; 95% CI 0.056-0.778) and a Charlson Comorbidity Index score of 2 or more (OR 0.173; 95% CI 0.041-0.733) were less likely to be referred to SPC. Pain (IRR 1.011; 95% CI 1.005-1.018), constipation (IRR 1.009; 95% CI 1.004-1.015), and impaired overall quality of life (IRR 0.991; 95% CI 0.983-0.999) were significantly associated with increased risk of hospital admissions. CONCLUSION: The study indicates a need for interventions in hospital departments to identify and manage the substantial symptom burden experienced by patients, provide palliative care, and ensure timely referral to SPC.

Prognostic Factors for Lymph Node Metastases in pT1 Colorectal Cancer Differ According to Tumor Morphology: A Nationwide Cohort Study.

OBJECTIVE: To investigate whether there is a differential impact of histopathological risk factors for lymph node metastases (LNM) in pedunculated and nonpedunculated pT1 colorectal cancers (CRC). BACKGROUND: Tumor budding, lymphovascular invasion (LVI), and venous invasion (VI) are recognized risk factors for LNM in pT1 CRC. Whether the importance of these factors varies according to tumor morphology is unknown. METHODS: Patients undergoing resection with lymphadenectomy for pT1 CRC in Denmark from January 2016 to January 2019 were identified in the Danish Colorectal Cancer Database and clinicopathological data was reviewed. Prognostic factors for LNM were investigated using multivariable analyses on the cohort as a whole as well as when stratifying according to tumor morphology (pedunculated vs. nonpedunculated). RESULTS: A total of 1167 eligible patients were identified, of whom 170 had LNM (14.6%). Independent prognostic factors for LNM included LVI [odds ratio (OR)=4.26, P <0.001], VI (OR=3.42, P <0.001), tumor budding (OR=2.12, P =0.002), high tumor grade (OR=2.76, P =0.020), and age per additional year (OR=0.96, P <0.001). On subgroup analyses, LVI and VI remained independently prognostic for LNM regardless of tumor morphology. However, tumor budding was only prognostic for LNM in pedunculated tumors (OR=4.19, P <0.001), whereas age was only prognostic in nonpedunculated tumors (OR=0.61, P =0.003). CONCLUSIONS: While LVI and LI were found to be prognostic of LNM in all pT1 CRC, the prognostic value of tumor budding differs between pedunculated and nonpedunculated tumors. Thus, tumor morphology should be taken into account when considering completion surgery in patients undergoing local excision.

Impact of adjuvant chemotherapy on long-term overall survival in patients with high-risk stage II colon cancer: a nationwide cohort study.

BACKGROUND: This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature. MATERIALS AND METHODS: Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration. RESULTS: In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p < 0.001. This association corresponded to an absolute risk difference of 14%. CONCLUSION: 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it.

Robot-assisted TAMIS: a systematic review of feasibility and outcomes.

BACKGROUND: In the advancement of transanal local excision, robot-assisted transanal minimal invasive surgery is the newest development. In the confined area of the rectum, robot-assisted surgery should, theoretically, be superior due to articulated utensils, video enhancement, and tremor reduction, however, this has not yet been investigated. The aim of this study was to review the evidence reported to-date on experience of using robot-assisted transanal minimal invasive surgery for treatment of rectal neoplasms. METHODS: A comprehensive literature search of Embase and PubMed from May to August 2021were performed. Studies including patients diagnosed with rectal neoplasia or benign polyps who underwent robot-assisted transanal minimal invasive surgery were included. All studies were assessed for risk of bias through assessment tools. Main outcome measures were feasibility, excision quality, and complications. RESULTS: Twenty-five studies with a total of 322 local excisions were included. The studies included were all retrospective, primarily case-reports, -series, and cohort studies. The median distance from the anal verge ranged from 3.5 to 10 cm and the median size was between 2.5 and 5.3 cm. Overall, 4.6% of the resections had a positive resection margin. The overall complication rate was at 9.5% with severe complications (Clavien-Dindo score III) at 0.9%. CONCLUSION: Based on limited, retrospective data, with a high risk of bias, robot-assisted transanal minimal invasive surgery seems feasible and safe for local excisions in the rectum.

Lymphovascular Infiltration, Not Depth of Invasion, is the Critical Risk Factor of Metastases in Early Colorectal Cancer: Retrospective Population-based Cohort Study on Prospectively Collected Data, Including Validation.

OBJECTIVE: To identify clinical and histopathological risk factors of LNM in T1 CRC. SUMMARY OF BACKGROUND DATA: The requisite of additional surgery after locally resected T1 CRC is dependent on the risk of LNM. Depth of submucosal invasion is used as a key predictor of lymphatic metastases although data are conflicting on its actual impact. METHODS: Retrospective population-based cohort study on prospectively collected data on all patients with T1 CRC undergoing surgical resection in Sweden, 2009-2017 and Denmark 2016-2018. The Danish cohort was used for validation. Potential risk factors of LNM investigated were; age, sex, tumor location, submucosal invasion, grade of differentiation, mucinous subtype, lymphovascular, and perineural invasion. RESULTS: One hundred fifty out of the 1439 included patients (10%) had LNM. LVI (P < 0.001), perineural invasion (P < 0.001), mucinous subtype (P = 0.006), and age <60 years (P < 0.001) were identified as independent risk factors whereas deep submucosal invasion was only a dependent (P = 0.025) risk factor and not significant in multivariate analysis (P = 0.075). The incidence of LNM was 51/882 (6%) in absence of the independent risk factors. The Danish validation cohort, confirmed our findings regarding the role of submucosal invasion, LVI, and age. CONCLUSIONS: This is a large study on LNM in T1 CRC, including validation, showing that LVI and perineural invasion, mucinous subtype, and low age constitute independent risk factors, whereas depth of submucosal invasion is not an independent risk factor of LNM. Thus, our findings provide a useful basis for management of patients after local excision of early CRC.

Fistula Laser Closure (FiLaC™) for fistula-in-ano-yet another technique with 50% healing rates?

PURPOSE: Treatment of ano-cutaneous fistulas remains a therapeutic challenge. Fistula Laser Closure (FiLaC™) is a relatively new technique for the treatment of ano-cutaneous fistulas. This study aimed to determine the success rate of fistula closure using FiLaC™. Secondary endpoints included adverse events and patient characteristics associated with treatment success. METHODS: This was a retrospective cohort study of consecutive patients subjected to FiLaC™ at Digestive Disease Center, Bispebjerg University Hospital, Copenhagen, between March 2017 and July 2019. All patients had a one-track fistula not suitable for fistulotomy. All were treated with a draining seton for at least 8 weeks prior to laser closure. Fistulas were ablated with a 360-degree emitting 12-watt 1470 nm laser probe. The inner fistula opening was closed with absorbable suture. All patients were followed with clinical examination including MRI or EAUS 1 year after the procedure. RESULTS: In total, 66 patients with 68 fistulas were included. Two patients had a high intersphincteric, 20 had low transsphincteric, 41 high transsphincteric and 5 had suprasphincteric fistulas. Fistula aetiology was cryptoglandular in 83.8%, whereas the rest were due to Crohn's disease. Thirty-one (45.6%) were subjected to a second FiLaC™ procedure. Follow-up was median 19 months (12-26 months). Ultimately, 30 of 68 (44.1%) of the fistulas healed. No cases of incontinence following FiLaC™ were observed, but a single patient developed an abscess. CONCLUSION: Fistula closure with FiLaC™ had success rates comparable to that of other sphincter-sparing techniques. The technique seems safe with respect to adverse events and risk of incontinence.

Treatment of chronic anal fissure: a feasibility study on Levorag® Emulgel versus Diltiazem gel 2.

PURPOSE: To compare the standard treatment, diltiazem gel 2%, with Levorag® Emulgel for chronic anal fissures. METHODS: This was a single-blinded, randomised, controlled, clinical trial with a non-inferiority design. Patients with a chronic anal fissure were randomised to treatment with diltiazem or Levorag® Emulgel twice daily for 8 weeks. Primary endpoint was complete healing of the anal fissure after 12 weeks. Secondary endpoints included incidence of adverse events and efficacy on pain relief. RESULTS: In total, 55 patients were included. Inclusion was terminated prematurely due to a slow inclusion rate. Complete fissure healing at 12 weeks follow-up was overall achieved in 31 of 55 (56%) patients, 18 of 29 (62%) in the diltiazem group compared with 13 of 26 (50%) in the Levorag® Emulgel group (P = 0.424). Pain relief was significantly better at day seven in patients treated with diltiazem (P = 0.040) compared with Levorag® Emulgel, whereas there were no differences in early (3 days) or late (12 weeks) pain relief. Three patients (10.3%) developed severe perianal exanthema during diltiazem treatment, whereas no side effects were observed in the Levorag® Emulgel group. CONCLUSION: The study demonstrated statistical non-inferiority of Levorag® Emulgel compared with diltiazem in the treatment of chronic anal fissure. Diltiazem resulted in a more prompt pain relief and also in a substantial number of local allergic reactions. Levorag® Emulgel may therefore be an alternative in these patients. TRIAL REGISTRATION: Clinicaltrials.gov no. NCT02158013.

Incidence of Incisional Hernia Repair After Laparoscopic Compared to Open Resection of Colonic Cancer: A Nationwide Analysis of 17,717 Patients.

BACKGROUND: It remains unknown whether laparoscopic compared to open surgery translates into fewer incisional hernia repairs (IHR). The objectives of the current study were to compare the long-term incidence of IHR and the size of repaired hernias between patients subjected to laparoscopic or open resection of colonic cancer. METHODS: This was a nationwide cohort study comprised of patients undergoing resection for colonic cancer between January 2007 and March 2016 according to the Danish Colorectal Cancer Group database. Patients who subsequently underwent IHR were identified in the Danish Ventral Hernia Database, from which information about the priority of the hernia repair and the size of the fascial defect was retrieved. RESULTS: The study included 17,717 patients, of whom 482 (2.7%) underwent subsequent IHR during a median follow-up of 4.7 (interquartile range 2.8-6.9) years. There was no significant difference in the 5-year cumulative incidence of hernia repair after laparoscopic compared to open colonic resection (3.9%, CI 3.3-4.4% vs 4.1%, CI 3.5-4.6%). After adjustment for confounders, laparoscopic approach was associated with an increased rate of emergency IHR (HR 2.37, 95% CI 1.03-5.46, P = 0.042) as opposed to elective IHR (HR 0.91, 95% CI 0.73-1.14, P = 0.442). Laparoscopic surgery was significantly associated with a decreased fascial defect area compared to open surgery (mean difference -16.0 cm2, 95% CI -29.4 to -2.5, P = 0.020). CONCLUSIONS: There was no difference in the incidence of IHR after open compared to laparoscopic resection. Compared to the open approach, laparoscopic resection increased the rate of subsequent emergency IHR, suggesting that a more aggressive therapeutic approach may be warranted in this patient group upon diagnosis of an incisional hernia.

Increased Leak Rates Following Stapled Versus Handsewn Ileocolic Anastomosis in Patients with Right-Sided Colon Cancer: A Nationwide Cohort Study.

BACKGROUND: Data on anastomotic leak rates after stapled versus handsewn ileocolic anastomosis are conflicting. In a Cochrane review, the combined estimate favored the stapled technique, but recent cohort studies demonstrated a 2-fold increase in anastomotic leak with the stapled approach. OBJECTIVE: The purpose of this study was to investigate anastomotic leak rates following stapled versus handsewn ileocolic anastomosis. DESIGN: This was a nationwide, retrospective cohort study. SETTING: Data were obtained from the Danish Colorectal Cancer Group and National Patient Registry databases. PATIENTS: Danish patients, ≥18 years of age, undergoing right hemicolectomy for a first-time diagnosis of adenocarcinoma in the right colon with primary anastomosis between October 2014 and December 2015 were included. MAIN OUTCOME MEASURES: The primary outcome was anastomotic leak rate. Secondary outcomes included 30-day mortality. Covariates included demographics, comorbidity, tumor stage, and surgical variables. Multivariable logistic regression and propensity score matching were used to adjust for confounding. RESULTS: The 1414 patients included 391 (28%) in the stapled group and 1023 (72%) in the handsewn group. Forty-five patients (3.2%) developed anastomotic leak: 21 of 391 (5.4%) and 24 of 1023 (2.4%) in the stapled and handsewn group (p = 0.004). This difference was confirmed in multivariable analysis (adjusted OR, 2.91; 95% CI, 1.53-5.53; p < 0.001), and after propensity score matching (OR, 2.41; 95% CI, 1.24-4.67; p = 0.009). Thirty-day mortality was 15.6% (7/45) and 2.1% (29/1369) in patients with and without anastomotic leak (p < 0.001), with no difference between the stapled and handsewn approach. LIMITATIONS: The study's design was retrospective, with no information on allocation to the stapled or handsewn approach. CONCLUSIONS: The present study demonstrated a 2-fold increase in anastomotic leak after stapled versus handsewn ileocolic anastomoses. Previous opinions on the optimal anastomosis technique for colon cancer should be scrutinized given the devastating short-term outcome of anastomotic leak. See Video Abstract at http://links.lww.com/DCR/A819.

Anastomotic Leakage After Stoma Reversal Combined with Incisional Hernia Repair.

BACKGROUND: Stoma reversal in patients with an incisional hernia represents a clinical dilemma, as it remains unknown whether hernia repair should be concomitantly employed. We aimed at examining postoperative complications and mortality in patients undergoing stoma reversal with or without concomitant hernia repair. METHODS: This study included all patients subjected to stoma reversal between 2010 and 2016 at our institution. Patients were grouped according to conductance of concomitant incisional hernia repair or not. The primary outcome was anastomotic leak (AL). Secondary outcomes were surgical site occurrences (SSO), overall surgical complications, 90-day mortality and overall survival. RESULTS: In total, 142 patients were included of whom 18 (13%) underwent concomitant hernia repair. The incidence of AL was significantly higher in patients subjected to concomitant hernia repair (four out of 18 [22.2%]) compared with patients undergoing stoma reversal alone (three out of 124 [2.4%], P = 0.002). Additional variables associated with AL were duration of surgery (P < 0.001) and ischemic heart disease (P = 0.039). Twenty-two patients (15.5%) developed a SSO: eight (44.4%) in the hernia repair group and 14 (11.3%) in the non-hernia repair group (P < 0.001). In the multivariable analysis, concomitant hernia repair remained significantly associated with development of postoperative complications (OR = 5.92, 95% CI = 1.54-25.96, P = 0.012). CONCLUSIONS: Compared with stoma reversal alone, incisional hernia repair concomitant with stoma reversal was associated with a higher incidence of AL and other complications.

Surgical management of acute cholecystitis in a nationwide Danish cohort.

PURPOSE: In the Danish national guidelines from 2006 on the treatment of acute cholecystitis, early laparoscopic operation within 5 days after the debut of symptoms was recommended. The aim of this study was to analyze the outcome in patients with acute cholecystitis subjected to cholecystectomy in Denmark in the five-year period hereafter. METHODS: All patients undergoing cholecystectomy in the period 2006-2010 were registered in the Danish Cholecystectomy Database, from which outcome data were collected. The effect of potential risk factors such as age, gender, BMI, American Society of Anesthesiologists (ASA) score, previous pancreatitis, previous abdominal surgery, year of operation, surgical approach, and surgeon experience was analyzed. RESULTS: Of 33,853 patients registered with a cholecystectomy, 4667 (14%) were operated for acute cholecystitis. In 95% of the patients, laparoscopic cholecystectomy was intended and in 5% primary open access was chosen. The frequency of conversion from laparoscopic to open surgery was 18%. High age and ASA score, operation in the early years of the period, and open or converted procedure all increased the risk of hospital stay to > 3 days or readmission. High age and ASA score, converted or open operation, and previous pancreatitis increased the risk of additional procedures. Postoperative mortality was 1.2%, and significant risk factors for postoperative death were age, low BMI, high ASA score, early year of operation, and open procedures. CONCLUSIONS: Acute cholecystectomy was safely managed laparoscopically in most patients after the introduction of national guidelines, with an increasing rate of laparoscopically completed procedures during the study period.

Oncological outcome following laparoscopic versus open surgery for cancer in the transverse colon: a nationwide cohort study.

BACKGROUND: The literature on transverse colonic cancer resection is sparse. The optimal surgical approach for this disease is thus unknown. This study aimed to examine laparoscopic versus open surgery for transverse colonic cancer. METHODS: This study was a nationwide, retrospective cohort study of all patients registered with a transverse colonic cancer in Denmark between 2010 and 2013. Data were obtained from the Danish Colorectal Cancer Group, the Danish Pathology Registry, Danish National Patient Registry, and patients' records. Main outcome measures were surgical resection plane, lymph node yield, and long-term cancer recurrence and survival. RESULTS: In total, 357 patients were included. Non-mesocolic resection was more frequent with laparoscopic compared with open resection (adjusted odds ratio 2.44, 95% CI 1.29-4.60, P = 0.006). Median number of harvested lymph nodes was higher after open compared with laparoscopic resection (22 versus 19, P = 0.03). Non-mesocolic resection (adjusted hazard ratio 2.45, 95% CI 1.25-4.79, P = 0.01) and increasing tumor stage (P < 0.001) were factors associated with recurrence. Cancer recurrence was significantly associated with an increased risk of mortality (adjusted hazard ratio 4.32, 95% CI 2.75-6.79, P < 0.001). Overall mortality was, however, not associated with the surgical approach or surgical plane. CONCLUSIONS: Although associated with a lower rate of mesocolic resection plane and fewer lymph nodes harvested, laparoscopic surgery for transverse colonic cancers led to similar long-term results compared with open resection.

Treatment of Complex Fistula-in-Ano With a Nitinol Proctology Clip.

BACKGROUND: The treatment of complex anocutaneous fistulas remains a major therapeutic challenge balancing the risk of incontinence against the chance of permanent closure. OBJECTIVE: The purpose of this study was to investigate the efficacy of a nitinol proctology clip for closure of complex anocutaneous fistulas. DESIGN: This is a single-center cohort study with retrospective analysis of all of the treated patients. SETTINGS: Data were obtained from patient records and MRI reports, as well as follow-up telephone calls and clinical follow-up with endoanal ultrasonography. PATIENTS: All of the patients were treated for high transsphincteric and suprasphincteric anocutaneous fistulas at the Digestive Disease Center, Bispebjerg Hospital, between May 2013 and February 2015. INTERVENTIONS: All of the patients were treated with the nitinol proctology clip. MAIN OUTCOME MEASURES: Primary outcome was fistula healing after proctology clip placement, as evaluated through clinical examination, endoanal ultrasonography, and MRI. RESULTS: The fistula healing rate 1 year after the clip procedure was 54.3% (19 of 35 included patients). At the end of follow-up, 17 (49%) of 35 patients had persistent closure of the fistula tracks. No impairment of continence function was observed. Treatment outcome was not found to be statistically associated with any clinicopathological characteristics. LIMITATIONS: The study is limited by its retrospective and nonrandomized design. Selection bias may have occurred, because treatment options other than the clip were available during the study period. The small number of patients means that there is a nonnegligible risk of type II error in the conclusion, and the follow-up may be too short to have detected all of the failures. CONCLUSIONS: Healing rates were comparable with those of other noninvasive, sphincter-sparing techniques for high-complex anocutaneous fistulas, with no risk of incontinence. Predictive parameters for fistula healing using this technique remain uncertain. See Video Abstract at http://links.lww.com/DCR/A347.

Differential Impact of Anastomotic Leak in Patients With Stage IV Colonic or Rectal Cancer: A Nationwide Cohort Study.

BACKGROUND: Anastomotic leak has a negative impact on the prognosis of patients who undergo colorectal cancer resection. However, data on anastomotic leak are limited for stage IV colorectal cancers. OBJECTIVE: The purpose of this study was to investigate the impact of anastomotic leak on survival and the decision to administer chemotherapy and/or metastasectomy after elective surgery for stage IV colorectal cancer. DESIGN: This was a nationwide, retrospective cohort study. SETTINGS: Data were obtained from the Danish Colorectal Cancer Group, the Danish Pathology Registry, and the National Patient Registry. PATIENTS: Patients who were diagnosed with stage IV colorectal cancer between 2009 and 2013 and underwent elective resection of their primary tumors were included. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality depending on the occurrence of anastomotic leak. Secondary outcomes were the administration of and time to adjuvant chemotherapy, metastasectomy rate, and risk factors for leak. RESULTS: Of the 774 patients with stage IV colorectal cancer who were included, 71 (9.2%) developed anastomotic leaks. Anastomotic leak had a significant impact on the long-term survival of patients with colon cancer (p = 0.04) but not on those with rectal cancer (p = 0.91). Anastomotic leak was followed by the decreased administration of adjuvant chemotherapy in patients with colon cancer (p = 0.007) but not in patients with rectal cancer (p = 0.47). Finally, anastomotic leak had a detrimental impact on metastasectomy rates after colon cancer but not on resection rates of rectal cancer. LIMITATIONS: Retrospective data on the selection criteria for primary tumor resection and metastatic tumor load were unavailable. CONCLUSIONS: The impact of anastomotic leak on patients differed between stage IV colon and rectal cancers. Survival and eligibility to receive chemotherapy and metastasectomy differed between patients with colon and rectal cancers. When planning for primary tumor resection, these factors should be considered.

Impaired collagen synthesis in the rectum may be a molecular target in anastomotic leakage prophylaxis.

The underlying molecular mechanisms for anastomotic leakage (AL) after colorectal surgery are unknown and there are no therapeutics for AL prevention. Our aim was to correlate endogenous matrix metalloproteinase (MMP) activity, collagen concentration, and collagen/MMP/cytokine mRNA levels with anatomic location in human colorectal tissue. We enrolled 22 patients in this prospective study: 7 underwent elective laparoscopic sigmoid resection and 15 underwent low anterior resection for colorectal cancer. Full-thickness intestinal tissue rings from anastomoses constructed with a circular stapler were used for the determination of the MMP activity, tissue collagen concentration and mRNA levels. COL1A1 (p = 0.017) and COL3A1 (p = 0.0013) mRNA levels were lower in rectal tissue than in colonic samples. Neither MMP activities nor collagen concentrations differed significantly between the two anatomic locations. By elucidating the factors responsible for the decreased collagen production we may identify specific molecular targets in AL prophylaxis.

Type of incision does not predict abdominal wall outcome after emergency surgery for colonic anastomotic leakage.

PURPOSE: Most literature on abdominal incision is based on patients undergoing elective surgery. In a cohort of patients with anastomotic leakage after colonic cancer resection, we analyzed the association between type of incision, fascial dehiscence, and incisional hernia. METHODS: Data were extracted from the Danish Colorectal Cancer Group database and merged with information from the Danish National Patient Register. All patients with anastomotic leakage after colonic resection in Denmark from 2001 until 2008 were included and surgical records on re-operations were retrieved. The primary outcome of the study was incisional hernia formation, and the secondary outcome was fascial dehiscence. Multivariable logistic, Cox, and competing risks regression analysis, as well as propensity score matching were used for confounder control. RESULTS: A total of 363 patients undergoing reoperation for anastomotic leakage were included with a median follow-up of 5.4 years. Incisional hernia occurred in 41 of 227 (15.3%) patients undergoing midline incision compared with 14 of 81 (14.7%) following transverse incision, P = 1.00. After adjusting for confounders, there was no association between the type of incision and incisional hernia (transverse incision hazard ratio 1.36, 0.68-2.72, P = 0.390) or fascial dehiscence (transverse incision odds ratio 1.66, 0.57-4.49, P = 0.331). This conclusion was confirmed after propensity score matching, P = 0.507. CONCLUSIONS: In the current study, type of incision did not predict abdominal wall outcome after emergency surgery for colonic anastomotic leakage.

Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon.

PURPOSE: Colonic obstruction causes loss of collagen and impairment of anastomotic integrity by matrix metalloproteinases (MMPs). Unexpectedly, pharmacological MMP inhibition increased anastomotic leakage (AL) in obstructed colon possibly due to the non-selective nature of these compounds and the experimental model applied. We therefore studied the effects of selective MMP inhibition on the healing of anastomoses in colon obstructed by a novel laparoscopic technique. METHODS: Left colon was obstructed in 38 male Sprague-Dawley rats (226-284 g). After 12 h, stenoses were resected and end-to-end anastomoses constructed. Baseline breaking strength was determined in 6 animals on day 0. The remaining 32 rats were randomized to daily treatment with the selective MMP-8, MMP-9, and MMP-12 inhibitor AZD3342 (n = 16) or vehicle (n = 16). On day 3, anastomoses were evaluated for AL and breaking strength. Isolated anastomotic wound tissue was analyzed on total collagen and pepsin-insoluble and pepsin-soluble collagen by hydroxyproline. The soluble collagens were further differentiated into native, measured by Sircol, and fragmented forms. RESULTS: Baseline breaking strength was maintained with AZD3342 but decreased by 25% (P = 0.023) in the vehicle group. The anastomotic breaking strength of AZD3342-treated rats was 44% higher (P = 0.008) than the vehicle-treated rats. Furthermore, the AL rate was reduced (P = 0.037) with AZD3342 compared with vehicle treatment. AZD3342 treatment influenced neither the total or insoluble collagen concentrations nor the degree of fragmentation of the soluble collagen triple helices. CONCLUSION: Selective MMP inhibition increased anastomotic breaking strength and reduced AL after resection of colonic obstruction.

The impact of incisional hernia on mortality after colonic cancer resection.

BACKGROUND: Long-term mortality after colonic cancer is not only related to the disease itself, but also to other factors such as surgical complications. Incisional hernia after abdominal surgery is a common complication; however, the impact on mortality is unknown. We thus sought to examine the impact of incisional hernia on mortality after colonic cancer resection. METHOD: This was a nationwide cohort study comprising data from the Danish Colorectal Cancer Group's database, the Danish National Patient Registry (NPR), and the Danish Central Person Registry. Patients who underwent curatively intended colonic resection for cancer with primary anastomosis between 2001 and 2008 were included. The exposure of interest was incisional hernia, as registered in the NPR, and the outcome was long-term overall mortality. Extended cox regression analysis was used to adjust for confounding variables including age, gender, comorbidity, tumor stage, and surgical approach at the index operation as well as postoperative anastomotic leakage, adjuvant chemotherapy and cancer recurrence. RESULTS: A total of 9214 patients were followed for median 6.4 years, during which 647 (7.0 %) were diagnosed with incisional hernia, 431 (4.7 %) underwent hernia repair, and 4631 (50.3 %) died. In the multivariable analysis, incisional hernia diagnosis was not associated with increased mortality (adjusted hazard ratio 0.81, 95 % confidence interval 0.70-0.93). Incarceration of the incisional hernia was associated with increased mortality (adjusted hazard ratio 2.35, 95 % confidence interval 1.39-3.98), while incisional hernia repair did not increase mortality (adjusted hazard ratio 0.81, 95 % confidence interval 0.68-0.97). CONCLUSIONS: Incisional hernia diagnosis or repair subsequent to colonic cancer resection did not increase mortality, albeit in the rare cases of incarceration.