The influence of delayed gastric emptying on quality of life after partial duodenopancreatectomy.

PURPOSE: Quality of life (QoL) is temporarily compromised after pancreatic surgery, but no evidence for a negative impact of postoperative complications on QoL has been provided thus far. Delayed gastric emptying (DGE) is one of the most common complications after pancreatic surgery and is associated with a high level of distress. Therefore, the aim of this study was to analyse the influence of DGE on QoL. METHODS: This single-centre retrospective study analysed QoL after partial duodenopancreatectomy (PD) via the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30). The QoL of patients with and without postoperative DGE was compared. RESULTS: Between 2010 and 2022, 251 patients were included, 85 of whom developed DGE (34%). Within the first postoperative year, compared to patients without DGE, those with DGE had a significantly reduced QoL, by 9.0 points (95% CI: -13.0 to -5.1, p < 0.001). Specifically, physical and psychosocial functioning (p = 0.020) decreased significantly, and patients with DGE suffered significantly more from fatigue (p = 0.010) and appetite loss (p = 0.017) than patients without DGE. After the first postoperative year, there were no significant differences in QoL or symptom scores between patients with DGE and those without DGE. CONCLUSION: Patients who developed DGE reported a significantly reduced QoL and reduced physical and psychosocial functioning within the first year after partial pancreatoduodenectomy compared to patients without DGE.

Systematic review on groove pancreatitis: management of a rare disease.

BACKGROUND: Groove pancreatitis is a focal form of chronic pancreatitis affecting the area of the paraduodenal groove. The aim of this systematic review was to assess the clinical presentation, diagnosis and treatment of patients with groove pancreatitis. METHODS: Medical literature databases (Embase, Medline via PubMed and Cochrane Central Register of Controlled Trials) were systematically searched for data recorded between 1 January 1990 and 31 August 2022 regarding patient characteristics, diagnosis, surgical treatment and outcomes. The following inclusion criteria were applied: RCTs, observational studies (cohort and case-control studies) and case studies with >3 cases including patients with groove pancreatitis undergoing medical, endoscopic or surgical treatment with available clinical and diagnostic data. Fisher's exact test for binary data and Mann-Whitney U test or Student t-test for continuous data were adopted for statistical analysis. RESULTS: Of 649 studies, 44 were included, involving reports on 1404 patients with a mean age of 49 years. In 41 of the 44 studies in which patient gender was described, 86 per cent (N = 1023) of patients were male. Information on the risk factors of alcohol and nicotine was available in 37 and 23 studies, respectively. Seventy-nine per cent (N = 886) of patients had a history of excessive alcohol consumption and 83 per cent (N = 595) were smokers. Information on clinical symptoms was available in 37 of the 44 included studies and 78.5 per cent (N = 870) presented with abdominal pain. Some 27 studies comprising 920 groove pancreatitis patients were treatment oriented. Seventy-four per cent (N = 682) of patients were treated conservatively, 26.4 per cent (N = 134) underwent endoscopic treatment and 54.7 per cent (N = 503) required surgery. There was complete relief of symptoms in 35.6 per cent (N = 243) after conservative treatment, 55.2 per cent (N = 74) after endoscopic treatment and 69.6 per cent (N = 350) after surgical treatment. The median follow-up time was 42 months (range, 1-161 months). CONCLUSION: Groove pancreatitis shows on imaging a typical triad: cystic lesions in the pancreatic duct or duodenal wall, calcifications, and thickenings of the duodenal wall. Surgery appears to be the most effective treatment modality.

Gum Chewing and Coffee Consumption but not Caffeine Intake Improve Bowel Function after Gastrointestinal Surgery: a Systematic Review and Network Meta-analysis.

BACKGROUND: Postoperative ileus is common after gastrointestinal surgery. This network meta-analysis aimed to compare the effectiveness of gum chewing and coffee and caffeine intake on ileus-related outcomes. METHODS: A systematic literature review was performed to identify randomized controlled trials (RCTs) comparing noninvasive treatments for ileus after gastrointestinal surgery. The main analyses included random effects network meta-analyses using frequentist methods with simultaneous direct and indirect comparisons of time to first flatus, time to first defecation, and length of stay. Bayesian network meta-analysis using Markov chains was also used. RESULTS: A total of 32 RCTs comparing 4999 patients were included in this network meta-analysis. Time to flatus was reduced by gum chewing (mean difference compared to control (MD): -11 h, 95% confidence interval (95% CI) - 16 to - 5 h, P < 0.001). Time to defecation was reduced by gum chewing and coffee, with MDs of -18 h (95% CI - 23 to - 13 h, P < 0.001) and -13 h (95% CI - 24 to - 1 h, P < 0.001), respectively. Length of stay was reduced by coffee and gum chewing with MDs of - 1.5 days (95% CI: - 2.5 to - 0.6 days, P < 0.001) and - 0.9 days (95% CI: - 1.3 to - 0.4 days, P < 0.001), respectively. CONCLUSION: Coffee and gum chewing were proven to be effective noninvasive approaches for shortening the postoperative length of hospital stay and time to first defecation, especially in open gastrointestinal surgery; thus these actions should be recommended after gastrointestinal surgery.

The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma.

Chemotherapy resistance is still a major problem in the treatment of patients with non-small-cell-lung carcinoma (NSCLC), and novel concepts for the induction of cytotoxicity in NSCLC are highly warranted. Proteotoxicity, the induction of cytotoxicity by targeting the ubiquitin proteasome system, represents an appealing innovative strategy. The combination of the proteasome inhibitor bortezomib (BTZ) and the proteotoxic stress-inducing HIV drug nelfinavir (NFV) synergistically induces proteotoxicity and shows encouraging preclinical efficacy in NSCLC. The second-generation proteasome inhibitor carfilzomib (CFZ) is superior to BTZ and overcomes BTZ resistance in multiple myeloma patients. Here, we show that CFZ together with NFV is superior to the BTZ + NFV combination in inducing endoplasmic reticulum stress and proteotoxicity through the accumulation of excess proteasomal substrate protein in NSCLC in vitro and ex vivo. Interestingly, NFV increases the intracellular availability of CFZ through inhibition of CFZ export from NSCLC cells that express multidrug resistance (MDR) protein. Combining CFZ with NFV may therefore represent a future treatment option for NSCLC, which warrants further investigation.

Caffeine for intestinal transit after laparoscopic colectomy: randomized clinical trial (CaCo trial).

BACKGROUND: Coffee has been suggested to help postoperative gastrointestinal motility but the mechanism is not known. This trial assessed whether caffeine shortened time to bowel activity after laparoscopic colectomy. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled superiority trial (October 2015 to August 2020). Patients aged at least 18 years undergoing elective laparoscopic colectomy were assigned randomly to receive 100 mg or 200 mg caffeine, or a placebo (250 mg corn starch) three times a day orally. The primary endpoint was the time to first bowel movement. Secondary endpoints included colonic transit time, time to tolerance of solid food, duration of hospital stay, and perioperative morbidity. RESULTS: Sixty patients were assigned randomly to either the 200-mg caffeine group (20 patients), the 100-mg caffeine group (20) or the placebo group (20). In the intention-to-treat analysis, the mean(s.d.) time to first bowel movement was 67.9(19.2) h in the 200-mg caffeine group, 68.2(32.2) h in the 100-mg caffeine group, and 67.3(22.7) h in the placebo group (P = 0.887). The per-protocol analysis and measurement of colonic transit time confirmed no measurable difference with caffeine. CONCLUSION: Caffeine was not associated with reduced time to first bowel movement. REGISTRATION NUMBER: NCT02510911 (http://www.clinicaltrials.gov).

Impact of precoding on reimbursement in diagnosis-related group systems: Randomized controlled trial.

BACKGROUND: Complete and correct documentation of diagnosis and procedures is essential for adequate health provider reimbursement in diagnosis-related group (DRG) systems. The objective of this study was to investigate whether daily monitoring and semiautomated proposal optimization of DRG coding (precoding) is associated with higher reimbursement per hospitalization day. MATERIALS AND METHODS: This parallel-group, unblinded, randomized clinical trial randomized patients 1:1 into intervention (precoding) and control groups. Between June 12 and December 6, 2019 all hospitalized patients (1566 cases) undergoing elective or emergency surgery at the department of surgery in a Swiss hospital were eligible for this study. By random sample selection, cases were assigned to the intervention (precoding) and control groups. The primary outcome was the total reimbursement, divided by the length of stay. RESULTS: Of the 1205 randomized cases, 1200 (precoding group: 602) remained for intention-to-treat, and 1131 (precoding group: 564) for per-protocol analysis. Precoding increased reimbursement per hospitalization day by 6.5% (160 US dollars; 95% confidence interval 31 to 289; P = 0.015). In a regression analysis patients hospitalized 7 days or longer, precoding increased reimbursement per day by 10.0% (246 US dollars; 95% confidence interval -12 to 504; P = 0.021). More secondary diagnoses (mean [SD]: 5.16 [5.60] vs 4.39 [5.34]; 0.77; 95% confidence interval 0.15 to 1.39; P = 0.015) and nonsurgical postoperative complications (mean [SD]: 0.68 [1.45] vs 0.45 [1.12]; 0.23; 95% confidence interval 0.08 to 0.38; P = 0.002) were documented by precoding. No associated was observed regarding the length of stay, total reimbursement, or case mix index. The mean (SD) precoding time effort was 37 (27) minutes per case. CONCLUSION: Physician-led precoding increases DRG-based reimbursement. Precoding is time consuming and should be focused on cases with a longer hospital stay to increase efficiency.

Diagnostic role of the 'white test' with lipidic solution in the early intraoperative identification of open bile ducts for the prevention of bile leakage after liver resection: study protocol for a randomised controlled multicentric superiority trial (BiLe-Trial).

INTRODUCTION: Bile leakage is a frequent complication after liver resection associated with the need of interventional drainage, endoscopic retrograde cholangio pancreatography (ERCP) or reoperation. The intraoperative application of the white test could be a promising strategy to reduce the occurrence of bile leakages. Therefore, we propose to conduct the first multicentric randomised controlled trial with rate of postoperative bile leakage as primary endpoint with and without the white test. METHODS AND ANALYSIS: The Bile-Leakage Trial trial is an investigator-initiated randomised controlled, parallel group, double-blinded, multicentric, superiority trial in four Swiss centres. A total of 210 patients undergoing a resection of at least 2 liver segments will be randomly allocated intraoperatively to either the intervention (identification of open bile ducts with administration of 20-40 mL SMOFlipid5% in the bile tract) or the control group (identification with a white gauze on the liver resection surface).Primary outcome will be the comparison of the postoperative bile leakage rate in both groups within 30 days after liver resection, defined according to the classification of the International Study Group of Liver Surgery. Secondary outcomes will be operative and postoperative complication, including severity grade of the bile leakage, rate of ERCP, interventional drainage, morbidity, intensive care unit stay, and mortality. ETHICS AND DISSEMINATION: The cantonal ethics committees of all participating centres and Swissmedic approved the study. SMOFlipid20% consists of a mixture of oils, no side effects resulting from the intraoperative application of 20-40 mL in the biliary tract with consecutive enteral absorption are expected nor are side effects described in the literature. SMOFlipid20% will be diluted intraoperatively with isotonic saline solution to a concentration of 5%. The results of the BiLe-Trial will be submitted to a peer-reviewed journal regardless of the outcome. As this is an investigator-initiated trial, data are property of the sponsor investigator and can be obtained on request. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID: NCT04523701. Registered on 25 August 2020.Swiss National Clinical Trials Portal (SNCTP), ID: SNCTP000004200. Registered on 20 January 2021. PROTOCOL VERSION: V3.2_14-12-2020_clean.pdf.

Still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival.

INTRODUCTION: Distant recurrence, especially liver metastases, occurs in one-third of rectal cancer patients initially treated with curative therapy and is still an unsolved problem. The identification of patients at risk is crucial for enabling individualized treatment. MATERIAL AND METHODS: All patients undergoing curative resection for histologically confirmed rectal cancer after neoadjuvant radiochemotherapy between January 2001 and December 2015 were included. Sections were stained for Ki67, CD44, apoptosis and CD133. Patients were categorized based on whether they were found to have (CD44+/Ki67+) or not have (CD44+/Ki67+) still proliferating tumor cells. RESULTS: 218 patients who underwent R0 resection for stage I-III rectal cancer were selected. In 37 (17%) of these patients, CD44+/Ki67+ tumor cells were found. In multivariable Cox regression analysis, patients with CD44+/Ki67+ cells had significantly impaired overall (hazard ratio (HR): 3.84, 95% CI: 1.77-8.31, p = 0.001) and relative survival (HR 3.44, 95% CI: 1.46-8.09). The previous results were confirmed after propensity-score matching. In mediation-analysis, the presence of CD44+/Ki67+ cells was associated with a substantial direct effect on overall (HR 1.92, 95% CI: 1.09-9.28) and relative survival (HR 1.63, 95% CI: 1.31-6.38). CONCLUSIONS: The presence of still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy was associated with impaired oncological long-term outcomes. Characterization of these cells should be performed.

Does Side Really Matter? Survival Analysis among Patients with Right- Versus Left-Sided Colon Cancer: A Propensity Score-Adjusted Analysis.

BACKGROUND: Right- and left-sided colon cancer are increasingly regarded as two independent disease entities based on different gene expression profiles as well as underlying genetic mutations. Data regarding prognosis and survival are heterogeneous and more favorable in cases of left-sided colon cancer. OBJECTIVE: The purpose of this study was to evaluate the long-term oncological outcome for patients with left-sided versus right-sided stage I-III colon cancer. METHODS: Overall, 318 consecutive patients who underwent surgery for right- or left-sided sided colon cancer between 2001 and 2014 were analyzed. Analysis was performed applying a prospectively maintained database with respect to overall, disease-specific, and relative survival, using Cox regression and propensity score analyses. RESULTS: A total of 155 patients (48.7%) presented with right-sided colon cancer and 163 patients (51.3%) presented with left-sided colon cancer. In risk-adjusted Cox regression analysis, tumor location had no significant impact on overall survival (hazard ratio [HR] 1.53, 95% confidence interval [CI] 0.80-2.92; p = 0.197), disease-specific survival (HR 1.36, 95% CI 0.76-2.44; p = 0.301), and relative survival (HR 1.70, 95% CI 0.89-3.27; p = 0.107). After propensity score matching, the results from risk-adjusted Cox regression analysis were confirmed. Stratified by American Joint Committee on Cancer stage, patients with right-sided stage II colon cancer had a statistically significant superior relative survival compared with patents with left-sided colon cancer. CONCLUSIONS: No significant negative impact on overall, disease-specific, or relative survival could be observed in patients with right- versus left-sided colon cancer after risk adjustment, using multivariable Cox regression and propensity score analyses.

Indeterminate dendritic cell tumor in the pancreas.

Indeterminate dendritic cell tumor (IDCT) is an extremely rare hematologic neoplastic disorder with proliferation of indeterminate dendritic cells. In the vast majority of cases, IDCTs are restricted to the skin or lymph nodes. To our knowledge, we report the first case of IDCT in the pancreas. Due to the rarity of extracutaneous IDCT, guidelines or treatment recommendations addressing their management are missing. We performed a review of literature to compare our experience to the management of other extracutaneous IDCT. Histopathological examination confirms the diagnosis of IDCT in electron microscopy and/or immunohistochemistry. Specific features are the lack of Birbeck granules and the nonreaction to Langerin antibodies. Concerning the aftercare of extracutaneous IDCT, we recommend a dermatological examination to rule out an additional cutaneous manifestation as well as annual blood examinations due to the association between IDCT and hematologic malignancies.

Effect of lymphadenectomy in curative gallbladder cancer treatment: a systematic review and meta-analysis.

PURPOSE: Only a small fraction of resectable gallbladder cancer (GBC) patients receive a thorough lymphadenectomy. The aim of this systematic review and meta-analysis was to investigate the effect of lymphadenectomy on survival in GBC surgery. METHODS: On May 19, 2019, MEDLINE, EMBASE, and the Cochrane Library were searched for English or German articles published since 2002. Studies assessing the effect of lymphadenectomy on survival in GBC surgery were included. Fixed effect and random effects models were used to summarise the hazard ratio (HR). RESULTS: Of the 530 identified articles, 18 observational studies (27,570 patients, 10 population-based, 8 cohort studies) were reviewed. In the meta-analysis, lymphadenectomy did not show a significant benefit for T1a tumours (n = 495; HR, 1.37; 95%CI, 0.65-2.86; P = 0.41). Lymphadenectomy showed a significant survival benefit in T1b (n = 1618; HR, 0.69; 95%CI, 0.50-0.94; P = 0.02) and T2 (n = 6204; HR, 0.68; 95%CI, 0.56-0.83; P < 0.01) tumours. Lymphadenectomy improved survival in the 2 studies assessing T3 tumours (n = 1961). A conclusive analysis was not possible for T4 tumours due to a low case load. Among patients undergoing lymphadenectomy, improved survival was observed in patients with a higher number of resected lymph nodes (HR, 0.57; 95%CI, 0.45-0.71; P < 0.01). CONCLUSIONS: Regional lymphadenectomy improves survival in T1b to T3 GBC. A minimum of 6 retrieved lymph nodes are necessary for adequate staging, indicating a thorough lymphadenectomy. Patients with T1a tumours should be evaluated for lymphadenectomy, especially if lymph node metastases are suspected.

Prognostic Impact of Lymph Node Excision in T1 and T2 Gallbladder Cancer: a Population-Based and Propensity Score-Matched SEER Analysis.

PURPOSE: The aim of this study was to assess the effect of lymphadenectomy on survival in T1/T2 gallbladder cancer (GBC). METHODS: In this retrospective cohort study, patients undergoing surgery for T1/T2 GBC from 2004 to 2014 were identified in the Surveillance, Epidemiology, and End Results database. The effect of lymph node excision (LNE) on survival was assessed using Cox regression and propensity score methods. RESULTS: A total of 2112 patients were identified: 11.4% had T1a, 18.5% T1b, and 70.1% had T2 tumors. Mean follow-up was 31.3 months. In 48.8% of patients, LNE was performed with a mean of 3.6 ± 4.3 nodes retrieved. Cancer-specific 5-year survival for T1 and T2 stages combined was 49.6% (95% confidence interval (CI), 45.9-53.6%) without LNE compared to 56.2% (95% CI, 52.4-60.4%) if LNE was performed (hazard ratio (HR), 0.75; 95%CI, 0.64-0.86, P < 0.001). Propensity score analyses for both stages combined confirmed this survival benefit with an HR of 0.67 (95% CI, 0.55-0.80) for the LNE group (P < 0.001). Stratified for tumor stages, LNE had no significant effect on cancer-specific survival in T1a (HR, 1.80 (95% CI, 0.76-4.26), P = 0.185) or T1b tumors (HR, 0.95 (95% CI, 0.57-1.58), P = 0.844), whereas it persistently revealed an advantage for patients with T2 tumors (HR 0.68 (95% CI, 0.55-0.83, P < 0.001). No correlation between the number of retrieved lymph nodes and the N+ rate was found (P = 0.134). CONCLUSIONS: LNE is associated with improved survival in T2 GBC. No significant survival benefit was observed in T1a and T1b tumors. The retrieval of even a few lymph nodes reliably predicts the nodal status, which might assist in patient selection for re-resection in T1 GBC.

Peridural analgesia does not impact survival in patients after colon cancer resection: a retrospective propensity score-adjusted analysis.

PURPOSE: To assess the putative impact of peridural analgesia on oncological outcome in patients undergoing resection of stages I-IV colon cancer. METHODS: In a single-center study, 876 patients undergoing resection for primary colon cancer (AJCC stages I-IV) between 2001 and 2014 were analyzed. Mean follow-up of the entire cohort was 4.2 ± 3.5 years. Patients who did and did not receive peridural analgesia were compared using Cox regression and propensity score analyses. RESULTS: Overall, 208 patients (23.7%) received peridural analgesia. Patients' characteristics were biased with regard to the use of peridural analgesia (propensity score 0.296 ± 0.129 vs. 0.219 ± 0.108, p < 0.001). After propensity score matching, the use of peridural analgesia had no impact on overall (HR 0.81, 95% CI 0.59-1.11, p = 0.175), cancer-specific (HR 0.72, 95% CI 0.48-1.09, p = 0.111), and disease-free survival (HR 0.89, 95% CI 0.66-1.19, p = 0.430). The 5-year overall survival after propensity score matching was 60.9% (95% CI 54.8-67.7%) for patients treated with peridural analgesia compared with 54.1% (95% CI 49.5-59.1%) for patients not treated with peridural analgesia. Cancer-specific and disease-free survival showed similar non-significant results. CONCLUSIONS: Peridural analgesia in patients after colon cancer resection was not associated with a better oncological outcome after risk adjusting in multivariable Cox regression and propensity score analyses. Hence, oncological outcome should not serve as a reason for the use of peridural analgesia in patients with colon cancer.

Urgent surgery in colon cancer has no impact on survival.

BACKGROUND AND OBJECTIVES: Despite advances in early detection of colon cancer, a minority of patients still require urgent surgery. Whether such urgent conditions result in poor outcome remains a topic of debate. METHODS: Using a prospectively maintained database, patients suffering exclusively from colon cancer and receiving either elective or emergent resection between 2001 and 2014 were analyzed with respect to overall, disease-specific, and relative survival using Cox regression and propensity score analyses. RESULTS: From a total of 877 patients analyzed, 2.7% (24) presented with complications requiring urgent surgery. Propensity-scoring identified strongly biased patient characteristics (0.097 ± 0.069 vs 0.028 ± 0.043; P < 0.001). An unadjusted Cox proportional hazards regression analysis revealed urgent surgery as a statistically significant prognostic factor with an approximately 207% increased risk of mortality (hazard ratio [HR] = 3.07; 95% confidence interval [CI]: 1.62-5.81; P = 0.003). After adjusting the data according to the propensity score analysis, urgent surgery was not associated with a decreased overall (HR = 1.67; 95%CI; 0.84-3.36; P = 0.174), disease-specific (HR = 1.62; 95% CI; 0.81-3.24; P = 0.201) or relative survival (HR = 1.86; 95% CI: 0.92-3.79; P = 0.086). CONCLUSIONS: After risk-adjustment, using multivariable Cox regression and propensity score analyses, no significant disadvantage could be noted with regard to overall, disease-specific, or relative survival in patients with exclusively colon cancer who received emergent oncological resection.

A Nomogram to Predict Anastomotic Leakage in Open Rectal Surgery-Hope or Hype?

BACKGROUND: Anastomotic leakage is the most dreaded complication after rectal resection and total mesorectal excision, leading to increased morbidity and mortality. Formation of a diverting ileostomy is generally performed to protect anastomotic healing. Identification of variables predicting anastomotic leakage might help to select patients who are under increased risk for the development of anastomotic leakage prior to surgery. The objective of this study was to assess the applicability of a nomogram as prognostic model for the occurrence of anastomotic leakage after rectal resection in a cohort of rectal cancer patients. METHODS: Nine hundred seventy-two consecutive patients who underwent surgery for rectal cancer were retrospectively analyzed. Univariate and multivariable Cox regression analyses were used to determine independent risk factors associated with anastomotic leakage. Receiver operating characteristics (ROC) curve analysis was performed to calculate the sensitivity, specificity, and overall model correctness of a recently published nomogram and an adopted risk score based on the variables identified in this study as a predictive model. RESULTS: Male sex (p = 0.042), obesity (p = 0.017), smoking (p = 0.012), postoperative bleeding (p = 0.024), and total protein level ≤ 5.6 g/dl (p = 0.007) were identified as independent risk factors for anastomotic leakage. The investigated nomogram and the adopted risk score failed to reach relevant areas under the ROC curve greater than 0.700 for the prediction of anastomotic leakage. CONCLUSIONS: The proposed nomogram and the adopted risk score failed to reliably predict the occurrence of anastomotic leakage after rectal resection. Risk scores as prognostic models for the prediction of anastomotic leakage, independently of the study population, still need to be identified.

Prognostic impact of anastomotic leakage after elective colon resection for cancer - A propensity score matched analysis of 628 patients.

BACKGROUND: There is limited information regarding the impact of anastomotic leakage on oncologic outcome in exclusively colon cancer patients. METHODS: The colorectal database of the Department of Surgery of the University of Heidelberg was used to assess the impact of anastomotic leakage on oncologic outcome in patients undergoing curative resection for Stage I-III colon cancer. Risk-adjusted Cox regression analysis and propensity score methods were used to assess overall, disease-free, and relative survival. RESULTS: 628 patients of which 26 (4.1%) experienced anastomotic leakage were analysed. Anastomotic leakage was associated with significantly worse overall, disease-free and relative survival in univariate and multivariate analysis. The analysis after exact propensity score matching confirmed the negative impact of anastomotic leakage on overall (HR 2.62, 95% CI 1.33-5.18, p = .011), disease-free (HR 2.28, 95% CI 1.16-4.47, p = .027) and relative survival (HR 3.70, 95% CI 1.82-7.52, p < .001). 5-year overall survival was 51.6% (95% CI 34.5-77.2%) for patients with anastomotic leakage compared to 77.7% (95% CI 73.0-82.8%) for patients without anastomotic leakage. CONCLUSIONS: All conceivable efforts should be made to avoid anastomotic leakage after colon resection for cancer not only to evade short-term consequences but also to allow for adequate long-term outcome.

CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses.

BACKGROUND: A particular characteristic of non-small cell lung cancer is the composition of the tumor microenvironment with a very high proportion of fibroblastic stromal cells (FSCs). OBJECTIVE: Lapses in our basic knowledge of fibroblast phenotype and function in the tumor microenvironment make it difficult to define whether FSC subsets exist that exhibit either tumor-promoting or tumor-suppressive properties. METHODS: We used gene expression profiling of lung versus tumor FSCs from patients with non-small cell lung cancer. Moreover, CCL19-expressing FSCs were studied in transgenic mouse models by using a lung cancer metastasis model. RESULTS: CCL19 mRNA expression in human tumor FSCs correlates with immune cell infiltration and intratumoral accumulation of CD8+ T cells. Mechanistic dissection in murine lung carcinoma models revealed that CCL19-expressing FSCs form perivascular niches to promote accumulation of CD8+ T cells in the tumor. Targeted ablation of CCL19-expressing tumor FSCs reduced immune cell recruitment and resulted in unleashed tumor growth. CONCLUSION: These data suggest that a distinct population of CCL19-producing FSCs fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.