Andreas Nordholm-Carstensen

Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study.

Objective:To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. Background:There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence. Methods:This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding. Results:The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL [adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI): 0.55–1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13–1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01–1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45–0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI: 12–20 days; P < 0.001). Conclusions:AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.

Occurrence and survival of synchronous pulmonary metastases in colorectal cancer: A nationwide cohort study

OBJECTIVE To investigate the occurrence of synchronous colorectal cancer metastases (SCCM) confined to the lungs, risk factors for these metastases and their impact on survival. METHODS In a nationwide cohort study of 26,200 patients data were prospectively entered into the Danish Colorectal Cancer Groups (DCCGs) database between May 2001 and December 2011. The recorded data were merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable logistic- and extended Cox regression analyses were used to adjust for confounding variables. RESULTS In total, 1970 patients (7.5%) had pulmonary SCCM of whom 736 (37%) had metastases exclusively in the lungs. Advanced age, recent years of diagnosis and a rectal index cancer were significantly associated with pulmonary SCCM. Adjustment for excess use of thoracic CT scans in rectal cancer patients did not alter this association (adjusted OR=1.81 (95% CI: 1.46-2.25, P<0.001)). Patients subjected to pulmonary metastasectomy, resection of primary tumour and chemotherapy had a superior overall survival compared with non-treated patients, especially when these therapeutic modalities were combined. CONCLUSIONS The occurrence of pulmonary SCCM was higher than previously reported and had a severe impact on survival. Our analyses suggest that pulmonary metastasectomy, resection of the primary tumour and chemotherapy may be a sound strategy in patients with confined pulmonary SCCM, but the risk of selection bias and consequent exaggeration of the treatment effect should be kept in mind. This study may serve as a reliable un-biased reference for future evaluation on detection strategies and potential therapeutic interventions.

Association of Comorbidity with Anastomotic Leak, 30-day Mortality, and Length of Stay in Elective Surgery for Colonic Cancer: A Nationwide Cohort Study.

BACKGROUND: Comorbidity has a negative influence on the long-term prognosis in patients with colorectal cancer, whereas its impact on the postoperative course is less clear. OBJECTIVES: The aim of this study was to investigate the influence of comorbidity on anastomotic leak and short-term outcomes after resection for colonic cancer. DESIGN: This is a retrospective nationwide cohort study SETTING: Data were obtained from the Danish Colorectal Cancer Group and the National Patient Registry. PATIENTS: Patients with colonic cancer undergoing elective resection between 2001 and 2008 were selected. MAIN OUTCOME MEASURES: The primary outcome was the ability of comorbidity to predict anastomotic leak. Secondary outcomes were 30-day mortality and length of stay. Comorbidity was assessed by the Charlson Comorbidity Index. Multivariable logistic regression and receiver operating characteristics curves were used to adjust for confounding. RESULTS: The rate of anastomotic leak was 535/8597 (6.2%). The mean (95% CI) Charlson score was 0.83 (0.72–0.94) and 0.63 (0.61–0.66) for patients with and without anastomotic leak, p < 0.001. The Charlson score, as assessed in the multivariable analysis (adjusted OR, 1.07; 95% CI, 0.99–1.15; p = 0.077) and by receiver operating characteristics curves (area under the curve = 0.548), failed to predict anastomotic leak. Thirty-day mortality was 425/8587 (4.9%). In patients with anastomotic leakage, a Charlson score of ≥2 was associated with increased mortality in comparison with a Charlson score of <2 (adjusted HR, 1.58; 95% CI, 1.00–2.51; p = 0.047). Mean length of stay was 8.7 days (95% CI, 8.4–9.2 days) for patients without an anastomotic leak in comparison with 23.3 days (95% CI, 21.5–25.1 days) for patients with anastomotic leak and 25.5 days (95% CI, 21.7–29.3 days) in patients with anastomotic leak and a Charlson score of >2, p < 0.001. LIMITATIONS: This study is limited by the accuracy of the coding used to generate the Charlson Comorbidity Index and the retrospective study design. CONCLUSION: Comorbidity failed to predict anastomotic leak, but it was associated with an inferior short-term outcome in patients with this surgical complication.

Diclofenac is associated with a reduced incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis: results from a Danish cohort study.

Objective The aim of this study was to assess the clinical effect of diclofenac administered as a single dose for the prevention of postprocedure pancreatitis in a consecutive series of patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP). Methods Patients with a native papilla Vateri subjected to ERCP during 2010 (control group, n = 218) and 2012 (diclofenac group, n = 182) were included. Patients with a history of chronic pancreatitis or recent acute pancreatitis were excluded. From January 2012, a rectal suppository containing 100 mg of diclofenac was administered immediately after endoscopy in all patients. The primary outcome of post-ERCP pancreatitis was assessed retrospectively by reviewing the patients’ charts. Results The overall incidence of post-ERCP pancreatitis was 32 (14.7%) of the 218 patients in the control group and 9 (4.9%) of the 182 patients in the diclofenac group (P = 0.002). Moderate to severe pancreatitis occurred in 22 (10.1%) of the 218 patients in the control group versus 8 (4.4%) of the 182 patients in the diclofenac group (P = 0.036). Conclusions This controlled cohort study suggests that the implementation of a single dose of 100 mg of diclofenac rectally administered significantly reduces the incidence of post-ERCP pancreatitis in an unselected material of patients with native papilla.

Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study.

The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Groups database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic‐ and Cox‐regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR) = 0.54 (95% confidence interval (CI):0.40–0.70, p < 0.001). The association only applied to confined hepatic metastases (aOR = 0.30, 95%CI: 0.18–0.49, p < 0.001), whereas the presence of confined pulmonary metastases (aOR = 0.71, 95% CI: 0.39–1.29, p = 0.258) or synchronous hepatic and pulmonary metastases (aOR = 0.69, 95% CI:0.26–1.29, p = 0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR) = 0.76, 95% CI: 0.54–1.06, p = 0.101; Proportional excess hazards: aHR = 0.73, 95% CI: 0.50–1.07, p = 0.111) when adjusting for other prognostic factors. The metastatic pattern varied according to MMR status. MMR had no impact on survival in patients with UICC Stage IV CRC. These findings may be important for the understanding of the metastatic processes and thus for optimizing staging and treatment in CRC patients.

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.

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

BackgroundThe 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.MethodsThis 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.ResultsIn 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.ConclusionsAlthough 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.

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.

Reply to Letter: "Anastomotic Leak Increases Distant Recurrence and Long-term Mortality After Curative Resection for Colonic Cancer".

Results: TheincidenceofALwas6.4%,744patientsdiedwithin120days.Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no associationtoAL[adjustedhazardratio(HR) =0.78;95%confidenceinterval (CI): 0.55‐1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13‐ 1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01‐1.44; P = 0.042). In 2841 patients with stageIIIcancer,ALwasassociatedwithbothdecreasedlikelihoodofreceiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45‐0.74; P < 0.001) andadelaytoinitialadministration(16days;95%CI:12‐20days;P <0.001). Conclusions: AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.

Pancreatic function following post-endoscopic retrograde cholangiopancreatography pancreatitis: A controlled cohort study with long-term follow-up:

Background Acute pancreatitis is one of the most common causes of gastrointestinal-related hospitalization and the incidence is increasing. Endo- and exocrine pancreatic function can be compromised after acute pancreatitis. Objective The purpose of this study was to explore the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on pancreatic function. Methods A follow-up study was carried out with prospective assessment of endo- and exocrine pancreatic function among cases with previous PEP and matched controls from a Danish cohort consisting of 772 patients undergoing first-time ERCP. Pancreatic function was evaluated by faecal-elastase-1 test, blood levels of haemoglobin A1c, C-peptide, vitamin B12, vitamin D and indirectly by changes in body weight. Results Twenty-nine cases and 49 controls participated in the study. Mean follow-up time (standard deviation) was 58 (21) months. Twelve (41%), eight (28%) and nine (31%) patients had mild, moderate and severe PEP, respectively. There was no difference between cases and controls with regard to pancreatic function parameters and PEP severity was not associated with pancreatic function. Factors associated with pancreatic function impairment included body mass index, alcohol consumption, age and smoking. Conclusion This study suggests that long-term pancreatic function following PEP is similar to the pancreatic function of other patients with comparable gallstone-related morbidity.