Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Therapy with pembrolizumab in treatment-naïve patients with nonmetastatic, mismatch repair deficient colorectal cancer.

Therapy with immune checkpoint inhibitors (ICI) is effective in patients with metastatic mismatch-repair deficient (dMMR) colorectal cancer (CRC); however, data on treatment with neoadjuvant ICI in patients with locally advanced CRC are limited. From March 2019 to June 2020, five Danish oncological centers treated 10 patients with a treatment-naïve dMMR CRC with preoperative pembrolizumab, 9 with a nonmetastatic, unresectable colon cancer and 1 with a locally advanced rectum cancer. All 10 patients were evaluated regularly at a multidisciplinary team (MDT) meeting, and they all had a radical resection after a median of 8 cycles (range 2-13) of pembrolizumab. A microscopic evaluation of the resected tumors revealed no remaining tumor cells in five patients, while five still had tumor cells present. The patients were given no additional therapy. No recurrences were reported after a median follow-up of 26 months (range 23-38.5 months). Biopsies from Danish patients with CRC are routinely screened for dMMR proteins. In 2017, data from the Danish Colorectal Cancer Group showed that 19% (565/3000) of the patients with colon cancer and 1.5% (19/1279) of those with rectum cancer had an dMMR tumor. Among the patients with MMR determination, 26% (99/384) patients had a T4 dMMR colon cancer; thus, the 10 patients treated with neoadjuvant pembrolizumab comprised about 9% of the patients with a T4 dMMR colon cancer (9/99) and 5% of patients with dMMR rectal cancer (1/19). Therapy with pembrolizumab was feasible and effective. Larger prospective trials are needed to confirm our findings.

Preoperative plasma vitamin D in patients with localized colorectal cancer: Age-dependent association with inflammation, postoperative complications, and survival.

INTRODUCTION: Aging is often associated with low-grade chronic inflammation and a senescent immune system. Vitamin D is a regulator of immune function, and low plasma vitamin D is associated with poor health. The association between plasma vitamin D and inflammatory biomarkers and risk of postoperative complications and survival in patients with colorectal cancer (CRC) is unknown. Our aim was to investigate these associations and how they are influenced by age. MATERIALS AND METHODS: Circulating vitamin D and the inflammatory biomarkers C-reactive protein (CRP), interleukin (IL)-6, and YKL-40 were measured in 398 patients with stage I-III CRC preoperatively. Older patients (≥70 years, n = 208) were compared to younger patients (<70 years, n = 190). The relation between vitamin D and complications and high inflammatory biomarker levels was presented by odds ratios ([OR], 95% confidence interval [CI]). Associations with survival were presented with hazard ratios ([HR], 95% CI). RESULTS: Plasma vitamin D was higher in older patients than in younger patients (75 vs. 67 nmol/L, P = 0.001). High vitamin D was associated with low plasma CRP in younger patients (OR = 0.35, 95% CI 0.17-0.76), but not in older patients (OR = 0.93, 0.49-1.76). High vitamin D in older patients with CRC was associated with reduced risk of major complications (OR = 0.52, 0.28-0.95). This was not found in younger patients (OR = 1.47, 0.70-3.11). Deficient vitamin D (<25 nmol/L) was associated with short overall survival compared to sufficient (>50 nmol/L) irrespective of age (HR = 3.39, 1.27-9.37, P = 0.02). CONCLUSION: For patients with localized CRC, high vitamin D levels before resection were associated with reduced risk of high inflammatory biomarkers for younger patients and reduced risk of major postoperative complications for older patients. Vitamin D deficiency was associated with reduced survival regardless of age.

The effect of intracorporeal versus extracorporeal anastomosis in robotic right colectomy on perianastomotic perfusion: a substudy to a multicenter RCT.

PURPOSE: Previous studies have shown that intracorporeal anastomosis (ICA) in minimally invasive right colectomy may improve postoperative recovery compared with extracorporeal anastomosis (ECA). It has been hypothesized that creating the anastomosis extracorporeally may cause mesenteric traction and compromised intestinal perfusion. The purpose of this study was to investigate the effect of either ICA or ECA on intestinal perfusion. METHOD: This was a substudy to a multicenter, triple-blind randomized clinical trial comparing ICA with ECA in patients undergoing robotic right colectomy for colonic cancer. Videos from intraoperative Indocyanine Green (ICG) fluorescence imaging were analyzed with quantitative ICG perfusion assessment (q-ICG). q-ICG was performed by extracting perfusion metrics from a time-intensity curve generated from an image analysis software: FMAX: maximal fluorescence intensity, TMAX: time until maximal fluorescent signal, T1/2MAX: time until half-maximal fluorescent signal, time ratio (T1/2MAX/TMAX) and slope. RESULTS: A total of 68 patients (33 ICA and 35 ECA) were available for analysis. Demographics were similar between the groups, except for mean arterial blood pressure at the time of ICG infusion, which was significantly lower in the ICA group. We found a significantly steeper slope in the ICA group compared to the ECA group (6.3 vs. 4.7 AU/sec, P = .048). There were no significant differences in FMAX, TMAX, T1/2MAX, and time ratio. CONCLUSION: We found evidence of an improved intestinal perfusion following ICA compared with ECA. This finding may be related to patient outcomes and should be explored further in the future. CLINICALTRIALS: gov NCT03130166.

Intracorporeal Versus Extracorporeal Anastomosis in Robotic Right Colectomy: A Multicenter, Triple-blind, Randomized Clinical Trial.

OBJECTIVE: To determine if minimally invasive right colectomy with intra-corporeal anastomosis improves postoperative recovery compared to extra-corporeal anastomosis. BACKGROUND: Previous trials have shown that intracorporeal anastomosis improves postoperative recovery; however, it has not yet been evaluated in a setting with optimized perioperative care or with patient-related outcome measures. METHODS: This was a multicenter, triple-blind, randomized clinical trial at two high-volume colorectal centers with strict adherence to optimized perioperative care pathways. The patients underwent robotic right colectomy with either intracorporeal or extracorporeal anastomosis. The primary outcome was patient-reported postoperative recovery measured using the "Quality of Recovery-15" questionnaire. ClinicalTrials.gov NCT03130166. RESULTS: A total of 89 patients were randomized and analyzed according to the "Intention-to-treat"-principle. We found no statistically significant differences in patient-reported recovery between the groups. Postoperative pain, nausea, time to ambulation, time to first passage of flatus/stool, length of hospital stay, and pathophysiological tests showed no differences either. The duration of time to create the anastomosis was significantly longer with intracorporeal anastomosis (17 vs 13 min, P = 0.003), while all other intraoperative, postoperative, and pathology variables showed no difference. CONCLUSION: There were no significant differences in postoperative recovery between the two groups.

Identification of Risk Factors Associated With Stage III Disease in Nonmetastatic Colon Cancer: Results From a Prospective National Cohort Study.

PURPOSE: This study aimed to identify possible patient- and tumor-related factors associated with risk of TNM stage III disease in nonmetastatic colon cancer. METHODS: The associations between stage III disease and age, sex, lymph node yield, pathological tumor (pT) stage, tumor subsite, type of surgery, and priority of surgery were assessed in a nationwide cohort of 13,766 patients treated with curative resection of colon cancer. Each level of age, lymph node yield, and pT stage was compared to the preceding level. RESULTS: Age, lymph node yield, pT stage, tumor subsite, and priority of surgery were associated with stage III disease. Odds ratios (95% confidence interval [CI]) were as follows: age < 65/65-75 years: 1.28 (95% CI, 1.15-1.43) and 65-75/ > 75 years: 1.22 (95% CI, 1.13-1.32); lymph node yield 0-5/6-11: 0.60 (95% CI, 0.50-0.72), lymph node yield 6-11/12-17: 0.84 (95% CI, 0.76-0.93), and lymph node yield 12-17/ ≥ 18: 0.97 (95% CI, 0.89-1.05); pT1/pT2: 0.74 (95% CI, 0.57-0.95), pT2/pT3: 0.35 (95% CI, 0.30-0.40), and pT3/pT4: 0.49 (95% CI, 0.47-0.54). Only tumors of the transverse colon were independently associated with lower risk of stage III disease than tumors in the sigmoid colon (sigmoid colon: 1, transverse colon: 0.84 [95% CI, 0.73-0.96]; elective surgery: 1, acute surgery: 1.43 [95% CI, 1.29-1.60]). CONCLUSION: In this study, stage III disease in colon cancer was significantly associated with age, lymph node yield, pT stage, tumor subsite, and priority of surgery but was not associated with right-sided location compared with stage I and II cancers.

Lymph node yield and tumour subsite are associated with survival in stage I-III colon cancer: results from a national cohort study.

BACKGROUND: It has been suggested that apart from tumour and nodal status, a range of patient-related and histopathological factors including lymph node yield and tumour location seems to have prognostic implications in stage I-III colon cancer. We analysed the prognostic implication of lymph node yield and tumour subsite in stage I-III colon cancer. METHODS: Data on patients with stage I to III adenocarcinoma of the colon and treated by curative resection in the period from 2003 to 2011 were extracted from the Danish Colorectal Cancer Group database, merged with information from the Danish National Patient Register and analysed. RESULTS: A total of 13,766 patients were included in the analysis. The 5-year overall survival ranged from 59.3% (95% CI 55.7-62.9%) (lymph node yield 0-5) to 74.0% (95% CI 71.8-76.2%) (lymph node yield ≥ 18) for patients with stage I-II disease (p < 0.0001) and from 36.4% (95% CI 29.8-43.0%) (lymph node yield 0-5) to 59.4% (95% CI 56.6-62.2%) (lymph node yield ≥ 18) for patients with stage III disease (p < 0.0001). The 5-year overall survival for tumour side left/right was 59.3% (95% CI 57.9-60.7%)/64.8% (CI 63.4-66.2%) (p < 0.0001). In the seven colonic tumour subsites, the 5-year overall survival ranged from 56.6% (95% CI 51.8-61.4%) at splenic flexure to 65.8% (95% CI 64.5-67.2%) in the sigmoid colon (p < 0.0001). In a cox regression analysis, lymph node yield and tumour side right/left were found to be prognostic factors. Tumours at the hepatic and splenic flexures had an adverse prognostic outcome. CONCLUSION: For stage I-III colon cancer, a lymph node yield beyond the recommended 12 lymph nodes was associated with improved survival. Both subsite in the right colon, as well as subsite in the left colon, turned out with adverse prognostic outcome questioning a simple classification into right-sided and left-sided colon cancer.

A high lymph node yield in colon cancer is associated with age, tumour stage, tumour sub-site and priority of surgery. Results from a prospective national cohort study.

AIM: To determine the relation between patient-related and histopathological factors, as well as the influence of national programs for diagnosing and treatment of colon cancer and a lymph node yield (LNY) ≥ 12. METHOD: An analysis was carried out of the LNY in a nationwide Danish cohort treated by curative resection of stage I-III colon cancer in the period 2003-2011. The association between a LNY ≥ 12 and age, sex, body mass index, open vs. laparoscopic surgery, acute vs. elective surgery, pT stage, tumour sub-site and year of diagnosis was analysed. RESULTS: A total of 13,766 patients were eligible for the analysis. In total, 71.4 % of the patients had a LNY ≥ 12. In multivariate analysis, age, pT stage, tumour sub-site and priority of surgery were independently associated with the probability of a LNY ≥ 12. Odds ratios (ORs) were as follows: age <65 1, 65-75 0.685 (confidence interval (CI) 0.586-0.800), >75 0.517 (CI 0.439-0.609); T1 1, T2 2.750 (CI 2.168-3.487), T3 6.016 (CI 4.879-7.418), T4 6.317 (CI 4.950-8.063); right colon 1, left colon 0.568 (0.511-0.633); elective surgery 1, acute surgery 0.748 (CI 0.625-0.894). Moreover, year of diagnosis was associated with the probability of a LNY ≥ 12: OR 1.480 (CI 1.445-1.516) for each increasing year in the study period. CONCLUSION: A LNY ≥ 12 is significantly associated with age, pT stage, tumour sub-site and priority of surgery. A significant increase in the LNY over the period of the study was observed, probably reflecting the effect of national programmes initiated by the Danish Colorectal Cancer Group.

Increased Lymph Node Yield Is Associated With Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment: Results From a National Cohort Study.

BACKGROUND: It has been proposed that the lymph node yield achieved during rectal cancer resection is associated with survival. It is debated whether a high lymph node yield improves survival, per se, or whether it does so by diminishing the International Union Against Cancer stage drifting effect. OBJECTIVE: The purpose of this study was to evaluate the prognostic implications of the lymph node yield in curative resected rectal cancer. DESIGN: This study was based on data from a prospectively maintained colorectal cancer database. SETTINGS: This was a national cohort study. PATIENTS: All 6793 patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages of patients with International Union Against Cancer stage III disease with a lymph node yield less than 12 or 12 or more were 28.1 % and 40.7% (p < 0.0001) in the non-neoadjuvant treatment group and 26.9% and 38.3% (p < 0.0001) in the neoadjuvant treatment group. The 5-year overall survival rates for patients with a lymph node yield <12 or 12 or more were 73.1% and 80.6% in International Union Against Cancer stages I to II (p < 0.0001) and 57.4% and 53.3% in stage III (p < 0.142) in the neoadjuvant treatment group and 70.4% and 79.2% in stages I to II (p < 0.0001) and 46.6% and 59.1% in International Union Against Cancer stage III (p < 0.0001) in the non-neoadjuvant treatment group. In multivariate analysis, the lymph node yield turned out to be an independent prognostic factor, irrespective of neoadjuvant treatment. LIMITATIONS: It is not possible in an observational study to tell whether the findings are associations rather than causal relationships. CONCLUSIONS: Increased lymph node yield was associated with better overall survival in rectal cancer, irrespective of neoadjuvant treatment. Stage migration was observed.

A minimum yield of twelve lymph nodes in rectal cancer remains valid in the era of neo-adjuvant treatment : results from a national cohort study.

PURPOSE: The purpose of the study was to examine if a minimum of 12 lymph nodes (LNs) is still valid in rectal cancer after neo-adjuvant treatment. METHODS: An analysis was carried out in a nationwide Danish cohort of 6793 patients, treated by curative resection of stage I-III rectal cancer during the period 2003-2011. The cohort was divided into two groups according to whether neo-adjuvant treatment had been given. The groups were analysed separately and were further analysed according to four lymph node yield (LNY) groups 0-5, 6-11, 12-17 and ≥18. RESULTS: Two thousand one hundred twenty-three patients (31.0 %) received neo-adjuvant treatment. A median LNY of 10 and 15 (p < 0.0001) and rates of node-positive (N-positive) disease of 31.6 and 36.7 % (p < 0.001) were observed with and without (+/-) neo-adjuvant treatment, respectively. The rate of N-positive disease according to tumour stage ranged from 4.8 %/11.4 % (ypT0/pT1) to 42.1 %/64.1 % (ypT4/pT4). The rate of N-positive disease according to LNY ranged from 19.5 %/16.8 % (0-5 LNs) to 42.6 %/37.9 % (≥18 LNs) (-/+neo-adjuvant treatment). In a logistic regression analysis, a significant association was found between N-positive disease and pT/ypT stage as well as between N-positive disease and LNY. CONCLUSIONS: A significantly smaller ratio of N-positive disease was observed in the group of patients who had received neo-adjuvant treatment. The ratio of N-positive disease increased significantly with more advanced tumour stage and increasing LNY irrespective of neo-adjuvant treatment. A minimum of 12 LNs is needed to ensure N-negative disease, irrespective of neo-adjuvant treatment.

[Perforated acute acalculous cholecystitis caused by hepatitis A].

Acute acalculous cholecystitis is a rare condition associated with a high risk of gangrene, empyema and perforation of the gallbladder. In this case report it is described how hepatitis A infection leads to a fulminant perforated acalculous chole-cystitis, which is described sporadically in the literature. The patient presented in this case report had icterus and highly elevated liver enzymes. Magnetic resonance cholangiopan-crea-tography showed an acalculous gallbladder surrounded by free fluid. Laparoscopic cholecystectomy was performed due to sus-picion of perforated acute acalculous cholecystitis.

A minority of patients discharged within 24 hours after laparoscopic colon resection.

INTRODUCTION: Fast-track laparoscopic colon surgery has gained wide acceptance worldwide. Post-operative hospital stays of 2-5 days have typically been reported. However, in our department some of the patients have been discharged within 24 h after surgery. The aim of this study was to describe differences in demographic and perioperative data between those patients discharged within 24 h and those discharged on days 2-4 post-operatively. MATERIAL AND METHODS: Data were collected retrospectively from August 2008 to May 2012. A total of 24 patients undergoing elective right-sided hemicolectomy or sigmoidectomy for colon cancer were discharged within 24 h. These 24 patients were compared with 209 patients undergoing the same procedures, but discharged on the second to the fourth post-operative day. All patients were operated laparoscopically according to our fast-track regimen. Demographic data and short-term outcomes were compared between the two groups. RESULTS: We found that the median age (64 years versus 70 years) (p = 0.018) as well as the median operating time (120 min. versus 155 min.) (p = 0.002) were significantly lower for the 24-h stay group. No other significant differences were found between the two groups. CONCLUSION: This study showed that discharge within the first 24 h after elective laparoscopic fast-track colon surgery was significantly associated with lower age and shorter duration of surgery. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

The majority of surgical departments adhere to national Danish guidelines for surveillance after colorectal cancer surgery.

INTRODUCTION: In 2003 the use of post-operative surveillance (POS) after surgery for colorectal cancer (CRC) in Denmark was studied. Diversity in the choice and frequency of surveillance modalities was found. Subsequently, the Danish Colorectal Cancer Group (DCCG) has published guidelines for POS. In the same period, the number of departments performing CRC surgery has been reduced by 50% nationally. The aim of the present study was to describe the POS after CRC in Denmark following a reduction in the number of departments performing operations for CRC and the DCCG's publication of national recommendations for POS programmes. MATERIAL AND METHODS: Questionnaires were sent to all 19 departments that performed operations for CRC. Questions concerned the diagnostic modalities used for detecting recurrences and metachrone cancers. RESULTS: All departments returned their questionnaires. All departments had a formal POS programme. The recommendations given by the DCCG were met by 17 departments (89%) with regard to liver metastases, by 16 departments (84%) with regard to lung metastases and by 16 departments (84%) with regard to metachrone cancers. CONCLUSION: As opposed to what was observed in 2003, all departments offered a POS programme after CRC surgery in 2012. Almost all departments met the DCCG recommendations, probably owing to the centralization of CRC surgery and the DCCG's introduction of national guidelines. Hopefully, this will contribute to a better survival for CRC patients in the future, although more research is needed to establish optimal post-operative surveillance. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Capsule endoscopy detection of metastasis of a malignant melanoma in the small intestine]. / Kapselendoskopisk påvisning af malignt melanom-metastase i tyndtarmen.

We report a case of a 74-year-old man with a Clark's level II, 2.5 mm melanoma on his back that was excised. A post-operative PET scan found no lesions. One and a half years later, the patient developed anaemia with blood in his stool. A gastroscopy and colonoscopy found no lesions. Video capsule endoscopy, however, detected a tumour in the small intestine. At laparotomy, the tumour was removed. Histological diagnosis showed metastatic malignant melanoma. We believe that video capsule endoscopy may increase the rate of diagnosis of small-bowel melanoma metastases.

[Heparin and cancer]. / Heparin og cancer.

The association between cancer and venous thromboembolism is well described. Several studies indicate that elements of the haemostatic system participate in tumour genesis. During the last decade a number of post-hoc analyses of trials not primarily designed to evaluate the effect of low molecular weight heparins (LMWH), on cancer survival, have indicated an increased survival. This has recently been supported by results from several prospective trials with LMWH. The possible anti-cancer effect of LMWH is not known in details. Treatment regimes with LMWH have to be performed.

Haemostatic alterations in colorectal cancer: perspectives for future treatment.

The role of the haemostatic system in colorectal cancer (CRC) is reviewed. Correlations between the activation of the haemostatic system and overall survival have been suggested. Experimental studies indicate that the haemostatic system plays a key role in growth, invasion and dissemination of tumour cells, and in tumour related angiogenesis. Additional activation by the surgical trauma and postoperative infections are discussed. Finally, anti-cancer modalities directed against regulation of the haemostatic system in CRC are considered.

Concentrations of VEGF and VEGFR1 in paired tumor arteries and veins in patients with rectal cancer.

Increased plasma concentrations of vascular endothelial growth factor (sVEGF) are associated with poor prognosis of colorectal cancer patients. The aim was to investigate the contribution of the tumor to plasma concentrations of VEGF and VEGF receptor 1 (VEGFR1). Preoperative blood samples from a peripheral vein and intraoperative blood samples from a tumor artery, a tumor vein, and from a peripheral vein were drawn from 28 patients undergoing elective surgical resection of primary rectal cancer. Plasma concentrations of VEGF and VEGFR1 were determined by ELISA. Counts of white blood cells and platelets were performed in all samples. No significant difference between plasma VEGF levels in the obtained blood samples was found (0.35 < P < 0.86). Plasma sVEGFR1 concentrations were significantly increased in tumor veins compared with tumor arteries. In addition, a significant reduction in plasma sVEGFR1 concentrations from preoperative to intraoperative samples was observed. There was a significant efflux of neutrophils to the tumor, but none of the observed changes in plasma VEGF or VEGFR1 levels correlated to changes in counts of white blood cells or platelets (sVEGF: 0.33 < P < 0.73 and sVEGFR1: 0.32 < P < 0.98). No changes in sVEGF plasma concentrations from tumor arteries to tumor veins were demonstrated, whereas there was a significant increase in sVEGFR1 from tumor arteries to tumor veins. Changes in sVEGF or sVEGFR1 from tumor arteries to tumor veins were not associated with changes in counts of white blood cells or platelets.