Prognostic Value of Metastatic Lymph Node Ratio and Identification of Factors Influencing the Lymph Node Yield in Patients Undergoing Curative Colon Cancer Resection.

Due to the impact of nodal metastasis on colon cancer prognosis, adequate regional lymph node resection and accurate pathological evaluation are required. The ratio of metastatic to examined nodes may bring an additional prognostic value to the actual staging system. This study analyzes the identification of factors influencing a high lymph node yield and its impact on survival. The lymph node ratio was determined in patients with fewer than 12 or at least 12 evaluated nodes. The study included patients after radical colon cancer resection in UICC stages II and III. For the lymph node ratio (LNR) analysis, node-positive patients were divided into four categories: i.e., LNR 1 (<0.05), LNR 2 (≥0.05; <0.2), LNR 3 (≥0.2; <0.4), and LNR 4 (≥0.4), and classified into two groups: i.e., those with <12 and ≥12 evaluated nodes. The study was conducted on 7012 patients who met the set criteria and were included in the data analysis. The mean number of examined lymph nodes was 22.08 (SD 10.64, median 20). Among the study subjects, 94.5% had 12 or more nodes evaluated. These patients were more likely to be younger, women, with a lower ASA classification, pT3 and pN2 categories. Also, they had no risk factors and frequently had a right-sided tumor. In the multivariate analysis, a younger age, ASA classification of II and III, high pT and pN categories, absence of risk factors, and right-sided location remained independent predictors for a lymph node yield ≥12. The univariate survival analysis of the entire cohort demonstrated a better five-year overall survival (OS) in patients with at least 12 lymph nodes examined (68% vs. 63%, p = 0.027). The LNR groups showed a significant association with OS, reaching from 75.5% for LNR 1 to 33.1% for LNR 4 (p < 0.001) in the ≥12 cohort, and from 74.8% for LNR2 to 49.3% for LNR4 (p = 0.007) in the <12 cohort. This influence remained significant and independent in multivariate analyses. The hazard ratios ranged from 1.016 to 2.698 for patients with less than 12 nodes, and from 1.248 to 3.615 for those with at least 12 nodes. The LNR allowed for a more precise estimation of the OS compared with the pN classification system. The metastatic lymph node ratio is an independent predictor for survival and should be included in current staging and therapeutic decision-making processes.

Multivisceral resection of advanced colon and rectal cancer: a prospective multicenter observational study with propensity score analysis of the morbidity, mortality, and survival.

Objectives: In the surgical treatment of colorectal carcinoma (CRC), 1 in 10 patients has a peritumorous adhesion or tumor infiltration in the adjacent tissue or organs. Accordingly, multivisceral resection (MVR) must be performed in these patients. This prospective multicenter observational study aimed to analyze the possible differences between non-multivisceral resection (nMVR) and MVR in terms of early postoperative and long-term oncological treatment outcomes. We also aimed to determine the factors influencing overall survival. Methods: The data of 25,321 patients from 364 hospitals who had undergone surgery for CRC (the Union for International Cancer Control stages I-III) during a defined period were evaluated. MVR was defined as (partial) resection of the tumor-bearing organ along with resection of the adherent and adjacent organs or tissues. In addition to the patients' personal, diagnosis (tumor findings), and therapy data, demographic data were also recorded and the early postoperative outcome was determined. Furthermore, the long-term survival of each patient was investigated, and a "matched-pair" analysis was performed. Results: From 2008 to 2015, the MVR rates were 9.9 % (n=1,551) for colon cancer (colon CA) and 10.6 % (n=1,027) for rectal cancer (rectal CA). CRC was more common in men (colon CA: 53.4 %; rectal CA: 62.0 %) than in women; all MVR groups had high proportions of women (53.6 % vs. 55.2 %; pairs of values in previously mentioned order). Resection of another organ frequently occurred (75.6 % vs. 63.7 %). The MVR group had a high prevalence of intraoperative (5.8 %; 12.1 %) and postoperative surgical complications (30.8 % vs. 36.4 %; each p<0.001). Wound infections (colon CA: 7.1 %) and anastomotic insufficiencies (rectal CA: 8.3 %) frequently occurred after MVR. The morbidity rates of the MVR groups were also determined (43.7 % vs. 47.2 %). The hospital mortality rates were 4.9 % in the colon CA-related MVR group and 3.8 % in the rectal CA-related MVR group and were significantly increased compared with those of the nMVR group (both p<0.001). Results of the matched-pair analysis showed that the morbidity rates in both MVR groups (colon CA: 42.9 % vs. 34.3 %; rectal CA: 46.3 % vs. 37.2 %; each p<0.001) were significantly increased. The hospital lethality rate tended to increase in the colon CA-related MVR group (4.8 % vs. 3.7 %; p=0.084), while it significantly increased in the rectal CA-related MVR group (3.4 % vs. 3.0 %; p=0.005). Moreover, the 5-year (yr) overall survival rates were 53.9 % (nMVR: 69.5 %; p<0.001) in the colon CA group and 56.8 % (nMVR: 69.4 %; p<0.001) in the rectal CA group. Comparison of individual T stages (MVR vs. nMVR) showed no significant differences in the survival outcomes (p<0.05); however, according to the matched-pair analysis, a significant difference was observed in the survival outcomes of those with pT4 colon CA (40.6 % vs. 50.2 %; p=0.017). By contrast, the local recurrence rates after MVR were not significantly different (7.0 % vs. 5.8 %; both p>0.05). The risk factors common to both tumor types were advanced age (>79 yr), pT stage, sex, and morbidity (each hazard ratio: >1; p<0.05). Conclusions: MVR allows curation by R0 resection with adequate long-term survival. For colon or rectal CA, MVR tended to be associated with reduced 5-year overall survival rates (significant only for pT4 colon CA based on the MPA results), as well as, with a significant increase in morbidity rates in both tumor entities. In the overall data, MVR was associated with significant increases in hospital lethality rates, as indicated by the matched-pair analysis (significant only for rectal CA).

Rectal Cancer: Are 12 Lymph Nodes the Limit?

Lymph node dissection is a crucial element of oncologic rectal surgery. Many guidelines regard the removal of at least 12 lymph nodes as the quality criterion in rectal cancer. However, this recommendation remains controversial. This study examines the factors influencing the lymph node yield and the validity of the 12-lymph node limit. Patients with rectal cancer who underwent low anterior resection or abdominoperineal amputation between 2000 and 2010 were analyzed. In total, 20,966 patients from 381 hospitals were included. Less than 12 lymph nodes were found in 20.53% of men and 19.31% of women (p = 0.03). The number of lymph nodes yielded increased significantly from 2000, 2005 and 2010 within the quality assurance program for all procedures. The univariate analysis indicated a significant (p < 0.001) correlation between lymph node yield and gender, age, pre-therapeutic T-stage, risk factors and neoadjuvant therapy. The multivariate analyses found T3 stage, female sex, the presence of at least one risk factor and neoadjuvant therapy to have a significant influence on yield. The probability of finding a positive lymph node was proportional to the number of examined nodes with no plateau. There is a proportional relationship between the number of examined lymph nodes and the probability of finding an infiltrated node. Optimal surgical technique and pathological evaluation of the specimen cannot be replaced by a numeric cut-off value.

Complete mesocolic excision for right colonic cancer: prospective multicentre study.

BACKGROUND: Complete mesocolic excision (CME) for right colonic cancer is a more complex operation than standard right hemicolectomy but evidence to support its routine use is still limited. This prospective multicentre study evaluated the effect of CME on long-term survival in colorectal cancer centres in Germany (RESECTAT trial). The primary hypothesis was that 5-year disease-free survival would be higher after CME than non-CME surgery. A secondary hypothesis was that there would be improved survival of patients with a mesenteric area greater than 15 000 mm2. METHODS: Centres were asked to continue their current surgical practices. The surgery was classified as CME if the superior mesenteric vein was dissected; otherwise it was assumed that no CME had been performed. All specimens were shipped to one institution for pathological analysis and documentation. Clinical data were recorded in an established registry for quality assurance. The primary endpoint was 5-year overall survival for stages I-III. Multivariable adjustment for group allocation was planned. Using a primary hypothesis of an increase in disease-free survival from 60 to 70 per cent, a sample size of 662 patients was calculated with a 50 per cent anticipated drop-out rate. RESULTS: A total of 1004 patients from 53 centres were recruited for the final analysis (496 CME, 508 no CME). Most operations (88.4 per cent) were done by an open approach. Anastomotic leak occurred in 3.4 per cent in the CME and 1.8 per cent in the non-CME group. There were slightly more lymph nodes found in CME than non-CME specimens (mean 55.6 and 50.4 respectively). Positive central mesenteric nodes were detected more in non-CME than CME specimens (5.9 versus 4.0 per cent). One-fifth of patients had died at the time of study with recorded recurrences (63, 6.3 per cent), too few to calculate disease-free survival (the original primary outcome), so overall survival (not disease-specific) results are presented. Short-term and overall survival were similar in the CME and non-CME groups. Adjusted Cox regression indicated a possible benefit for overall survival with CME in stage III disease (HR 0.52, 95 per cent c.i. 0.31 to 0.85; P = 0.010) but less so for disease-free survival (HR 0.66; P = 0.068). The secondary outcome (15 000 mm2 mesenteric size) did not influence survival at any stage (removal of more mesentery did not alter survival). CONCLUSION: No general benefit of CME could be established. The observation of better overall survival in stage III on unplanned exploratory analysis is of uncertain significance.

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

BACKGROUND AND AIMS: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC. METHODS: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire. RESULTS: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001). CONCLUSIONS: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research.

OBJECTIVES: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. METHODS: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. RESULTS: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p = 0.001). CONCLUSIONS: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

[Morbidity and Mortality of Single Incision Cholecystectomy: Results of a 3-Year Register Analysis]. / Morbidität und Letalität der Single-Incision-Cholezystektomie: eine 3-Jahres-Registeranalyse.

INTRODUCTION: Two decades ago, single-incision surgery was established as a new concept in minimally invasive surgery. Single incision cholecystectomy is the most frequently performed procedure in clinical routine. Most of the results have been based on randomised trials. Large prospective multicentre observational datasets from clinical routine do not exist. This analysis of clinical health service research is based on the SILAP study (single-incision multiport/single port laparoscopic abdominal surgery study). PATIENTS AND METHODS: The data of the register were collected in 47 hospitals in the period of 2012 to 2014. Overall morbidity and mortality were the primary outcome. Multiple linear and logistic regression analyses were performed. Statistical significance was set at p < 0.05. RESULTS: Data from 975 patients in clinical routine with single incision cholecystectomy were collected. Intraoperative complications were recorded in 3.2% of cases. Bile duct injuries were registered in 0.1% of cases. Postoperative complications were detected in 3.7% of cases. The mortality rate was 0.2%.The median operating time dropped from 60.0 to 51.5 min (p < 0.001) during the study. The use of an extra trocar was necessary in 10.3% of cases. Conversion to open surgery was performed in 0.7% of cases. Body mass index (p = 0.024), male gender (p = 0.012) and operating time (p < 0.001) had a significant effect on intraoperative complications in multivariate analysis. Classification of ASA III (p = 0.001) and modification or conversion of single incision technique (p = 0.001) were significantly associated with postoperative complications. CONCLUSION: The register analysis of the prospective multicentre data shows that single incision cholecystectomy is feasible in clinical routine even outside the selective criteria of randomised studies. The only limitation is a BMI > 30 kg/m2 which has a significant influence on the intraoperative rate of complications in mild adverse events.

Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison.

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of ≥80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

Surgical Quality in Rectal Cancer Management: What Can Be Achieved by a Voluntary Observational Study?

PURPOSE: Countries with nationwide quality programmes in colorectal cancer report an improved outcome. In Germany, a self-organized and self-financed observational quality assurance project exists, based on voluntary participation. The object of the present study was to ascertain whether this nationwide project also improves the outcome of colorectal cancer. METHODS: The German Quality Assurance in Colorectal Cancer Project started in 2000 and by 2012 contained 85,000 patients. Inclusion criteria for the study were participation for the entire period of 13 years and treatment of rectal cancer. The following parameters were analysed: (1) patient related: age, gender, ASA classification, T-stage, and N-stage, (2) system related: frequency of preoperative CT and MRI, and (3) outcome related: CRM status, complications, and hospital mortality. RESULTS: Forty-one of the 345 hospitals treating 11,597 patients fulfilled the inclusion criteria. The median age increased from 67 to 69 years (p = 0.002). ASA stages III and IV increased from 32.0% to 37.6% (p = 0.005) and from 2.0% to 3.3% (p = 0.022), respectively. The use of CT rose from 67.2% to 88.8% (p < 0.001) and that of MRI from 5.0% to 35.2% (p < 0.001). The proportion of patients suffering from complications decreased from 7.9% to 5.3% (p < 0.001) for intraoperative and from 28.0% to 18.6% (p < 0.001) for postoperative surgical complications, but general postoperative complications increased from 25.8% to 29.5% (p = 0.006). The distribution of histopathological stage, anastomotic leakage, and in-hospital mortality did not change significantly. CONCLUSION: Participation in a quality assurance project improves compliance with treatment standards, especially for diagnostic procedures. An improvement of surgical results will require further investment in training.

Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison.

BACKGROUND: Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. SUBJECTS, MATERIALS, AND METHODS: National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. RESULTS: Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II-IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96) compared with Belgium. CONCLUSION: There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. IMPLICATIONS FOR PRACTICE: With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.

Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study.

PURPOSE: The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. METHODS: We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. RESULTS: The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. CONCLUSION: The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.

[Roux-Y-Gastric Bypass for Morbid Obesity in Adolescents: Is it as Safe and Effective as in Obese Adults?] / Der Roux-Y-Magenbypass zur Therapie der Adipositas bei Jugendlichen: Analyse des Gewichtsverlaufs und des Einflusses auf Komorbiditäten im Vergleich zu adipösen Erwachsenen.

BACKGROUND: Obesity is one of the major challenges of the 21st century. There is also an increasing incidence of obesity in adolescents. Bariatric surgery has been proven safe and effective in obese adults. In adolescents, these operations are still subject to controversy. Current evidence is limited regarding its safety and outcome in this age group. METHODS: Within the German Bariatric Surgery Registry, data from obese patients that underwent bariatric procedures in Germany are prospectively registered. The current analysis includes all adolescent and adult subjects that underwent primary Roux-Y-gastric bypass (RYGB) surgery from 2005 to 2014. RESULTS: Overall, 370 adolescents (≤ 21 years) and 16,840 obese adults were enrolled. In 2014, RYGB was the second most common bariatric procedure in Germany. In the adolescent group, initial BMI was higher (49.2 vs. 47.9 kg/m2, p < 0.01); the proportion of associated comorbidities was lower (67.8 vs. 87.4%, p < 0.01). Operation time (104.9 vs. 113.0 min, p < 0.01) and hospital stay (5.2 vs. 5.9 days; p < 0.01) differed significantly between both groups. The leakage rate in adults was 1.6%; none of the adolescents experienced a postoperative anastomotic leak (p = 0.04). No mortalities were reported in adolescents; the mortality rate in adults was 0.2%. The mean percentage of excess weight loss (% EWL) did not differ between both groups at 12 (69.9 vs. 68.2%; p = 0.97) and 24 months (72.6 vs. 72.1% p = 1.0). The remission rate for hypertension was higher in the adolescent group. CONCLUSION: RYGB can be performed in obese adolescents with lower morbidity and mortality. Despite all limitations of a multicentre registry and the low follow-up rate, the results show that weight change and resolution of comorbidities in the short term were at least comparable to those achieved in adults. The evaluation of safety and efficiency in the long run should now be in the focus of future studies.

[How does Diabetes Mellitus Influence Early Postoperative Results and Survival in Rectal Cancer?] / Wie beeinflusst der Diabetes mellitus das frühpostoperative und onkochirurgische Langzeit-"Outcome" beim Rektumkarzinom?

INTRODUCTION: Aim of this study was to investigate the influence of diabetes mellitus (DM) onto the early postoperative and long-term oncosurgical outcome after surgery for rectal cancer using data prospectively obtained in a representative number of patients. METHODS: Data (using a registration form of 68 items) from the ongoing multicenter observational study "rectal cancer (primary tumor) - elective surgery" on Quality Assurance was used including years 2008 to 2011. A voluntary and frequent follow-up was done to gain long-term data. Patients were grouped as non-diabetic and not-/insulin-dependent DM (NIDDM/IDDM). RESULTS: In total, 10 442 patients were enrolled; 11.0 % had NIDDM and 7.2 % IDDM. Average age of patients without DM was 67.3 [95 %-CI: 67,07; 67,55] years (yr) and was lower than in IDDM- (71.7 [95 %-CI: 71,01; 72,35] yr) and NIDDM-patients (70.9 [95 %-CI: 70.41; 71.45] yr) (p < 0.001). Tumor stages according to classification by UICC were comparable (p = 0.547). Patients with DM were more likely to be obese and to have cardiovascular and renal risk factors as well as a more critical ASA-classification (p < 0.001 each). Postoperative morbidity (in the group 65 - 74 yr; p = 0.006) and in-hospital mortality (< 65 yr; p = 0.011) was higher in patients with DM. The 5-year overall survival (OS) was 60.6 % in patients without DM. IDDM (46.4 %) and NIDDM (53.3 %) decreased the OS (p < 0.001 each). The 5-year disease-free survival (DFS) was also worsened by IDDM (p < 0.001) and NIDDM (p = 0.004). No difference was observed concerning 5-year local recurrence rate, neither for IDDM (p = 0.524) nor NIDDM (P = 0.058). DISCUSSION: The metabolic disorder DM has a significant impact onto the outcome after surgery for rectal cancer most likely due to its own risk potential and associated comorbidities. Postoperative morbidity and mortality were increased and the oncological survival was worsened.

Impact of Body Mass Index on Early Postoperative and Long-Term Outcome after Rectal Cancer Surgery.

BACKGROUND: The aim of this study was to investigate the impact of obesity and underweight onto early postoperative and long-term oncological outcome after surgery for rectal cancer. METHODS: Data from 2008 until 2011 was gathered by a German prospective multicenter observational study. 62 items were reported by the physicians in charge, and a consecutive follow-up was performed if the patient had signed a consent form. Patients were subclassified into: underweight, normal weight, overweight, and obese - using the definitions of the World Health Organization. RESULTS: In total, 9,920 patients were included, of whom 2.1% were underweight and 19.4% obese. The mean age was 68 years (range 21-99 years). Postoperative morbidity (mean 38.0%) was significantly increased in underweight and obese patients (p < 0.001). In-hospital mortality was 3.1% on average with no significant differences among patient groups (p = 0.176). The 5-year overall survival ranged between 36.9 and 61.3% and was worse in underweight and prolonged in overweight and obese patients compared to those with normal weight (p < 0.001 each). While the 5-year disease-free survival was increased in overweight and obese patients (p < 0.05 each), the 5-year local recurrence rate showed no correlation (p > 0.05 each). Multivariate analysis revealed that advanced age, higher ASA scoring, postoperative morbidity, and advanced tumor growth worsened the long-term survival independently. CONCLUSIONS: Underweight patients had a worse early and long-term outcome after rectal cancer surgery. Overweight and obesity were associated with a significantly better long-term survival.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. DESIGN: Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. DISCUSSION: Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006179 .

Perioperative Course, Weight Loss and Resolution of Comorbidities After Primary Sleeve Gastrectomy for Morbid Obesity: Are There Differences Between Adolescents and Adults?

BACKGROUND: Morbid obesity in both adolescents and adults has risen in an alarming rate. Bariatric surgery is playing an increasing role in pediatric surgery. However, current evidence is limited regarding its safety and outcome. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adolescent and adult subjects that had undergone laparoscopic sleeve gastrectomy (LSG) from 2005 to 2014 were considered. RESULTS: LSG represents the most common bariatric procedure in Germany with a proportion of 48.1% in adolescent and 48.7% in adult obese in 2014. LSG was performed in 362 adolescent and 15,428 adult subjects. Pre-operative BMI was comparable between the two populations. However, adult obese had more frequently coexisting comorbidities (p < 0.01). Complication rates and mortality (0 vs. 0.2%) did not differ significantly. Adolescents achieved a BMI reduction of 16.8 and 18.0 kg/m2 at 12 and 24 months compared with 15.4 and 16.6 kg/m2 in the adult group. There was a significantly higher BMI reduction in late adolescents (19-21 years) compared with patients ≤18 years at 24 months (19.8 vs. 13.6 kg/m2). Resolution rate of hypertension was significantly higher in adolescents. CONCLUSION: LSG is a safe therapeutic option that can be performed in adolescents without mortality. Late adolescents experienced the highest weight loss; resolution rate of comorbidities was lower in adults. All future efforts should now be focused on the evaluation of the long-term outcomes of LSG in the pediatric population.

Staple Line Leak After Primary Sleeve Gastrectomy-Risk Factors and Mid-term Results: Do Patients Still Benefit from the Weight Loss Procedure?

BACKGROUND: Staple line leak after laparoscopic sleeve gastrectomy (LSG) still represents the most feared complication. The purpose of this study was to investigate whether there are factors that increase the risk for a leakage. Furthermore, we aimed to analyze the impact of a leak on weight change and resolution of comorbidities. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adult subjects that had undergone primary LSG from 2005 to 2014 were considered. RESULTS: Overall, 241/15,756 (1.53%) patients experienced a leak. The occurrence of a leakage resulted in a significant increase of the mortality rate (3.7 vs. 0.2%; p < 0.01). Percent excess weight loss did not differ between leak and non-leak patients, both, at 12 (64.2 vs. 60.9%; p = 1.0) and 24 months (68.5 vs. 64.0%, p = 0.86). Similarly, no significant difference was observed for resolution rate of all comorbid conditions. Matched pair analysis confirmed these findings. Multivariable analysis identified operation time, conversion, intraoperative complications, and hypertension and degenerative joint disease as risk factors for a leak. Oversewing the staple line was associated with the lowest risk. CONCLUSION: The postoperative staple line leak after primary LSG significantly increases postoperative morbidity and mortality. We found that there are patient-related factors and operative variables that predispose to leakage after LSG. However, the occurrence of a leakage does not adversely impact the weight loss and resolution of comorbidities in the mid-term.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

AIMS: Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. METHOD: Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. RESULTS: Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. CONCLUSION: In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study.

BACKGROUND: Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. OBJECTIVE: This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients' perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. METHODS: The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. RESULTS: Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). CONCLUSIONS: This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http://www.webcitation.org/6jK6ZVyUs).

Risk factors, short and long term outcome of anastomotic leaks in rectal cancer.

BACKGROUND: An anastomotic leak (AL) after colorectal surgery is one major reason for postoperative morbidity and mortality. There is growing evidence that AL affects short and long term outcome. This prospective German multicentre study aims to identify risk factors for AL and quantify effects on short and long term course after rectal cancer surgery. METHODS: From 1 January 2000 to 31 December 2010 381 hospitals attributed patients to the prospective multicentre study Quality Assurance in Colorectal Cancer managed by the Otto-von-Guericke-University Magdeburg (Germany). Included were 17 867 patients with histopathologically confirmed rectal carcinoma and primary anastomosis. Risk factor analysis included 13 items of demographic patient data, surgical course, hospital volume und tumour stage. RESULTS: In 2 134 (11.9%) patients an AL was diagnosed. Overall hospital mortality was 2.1% (with AL 7.5%, without AL 1.4%; p < 0.0001). In multivariate analysis male gender, ASA-classification ≥III, smoking history, alcohol history, intraoperative blood transfusion, no protective ileostomy, UICC-stage and height of tumour were independent risk factors. Overall survival (OS) was significantly shorter for patients with AL (UICC I-III; UICC I, II or III - each p < 0.0001). Disease free survival (DFS) was significantly shorter for patients with AL in UICC I-III; UICC II or UICC III (each p < 0.001). Rate of local relapse was not significantly affected by occurrence of AL. CONCLUSIONS: In this study patients with AL had a significantly worse OS. This was mainly due to an increased in hospital mortality. DFS was also negatively affected by AL whereas local relapse was not. This emphasizes the importance of successful treatment of AL related problems during the initial hospital stay.