Obesity in Humans Is Characterized by Gut Inflammation as Shown by Pro-Inflammatory Intestinal Macrophage Accumulation.

Chronic low-grade inflammation is a hallmark of obesity and associated with cardiovascular complications. However, it remains unclear where this inflammation starts. As the gut is constantly exposed to food, gut microbiota, and metabolites, we hypothesized that mucosal immunity triggers an innate inflammatory response in obesity. We characterized five distinct macrophage subpopulations (P1-P5) along the gastrointestinal tract and blood monocyte subpopulations (classical, non-classical, intermediate), which replenish intestinal macrophages, in non-obese (BMI<27kg/m2) and obese individuals (BMI>32kg/m2). To elucidate factors that potentially trigger gut inflammation, we correlated these subpopulations with cardiovascular risk factors and lifestyle behaviors. In obese individuals, we found higher pro-inflammatory macrophages in the stomach, duodenum, and colon. Intermediate blood monocytes were also increased in obesity, suggesting enhanced recruitment to the gut. We identified unhealthy lifestyle habits as potential triggers of gut and systemic inflammation (i.e., low vegetable intake, high processed meat consumption, sedentary lifestyle). Cardiovascular risk factors other than body weight did not affect the innate immune response. Thus, obesity in humans is characterized by gut inflammation as shown by accumulation of pro-inflammatory intestinal macrophages, potentially via recruited blood monocytes. Understanding gut innate immunity in human obesity might open up new targets for immune-modulatory treatments in metabolic disease.

Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy.

Tutorial Assistance for Board Certification in Surgery: Frequency, Associated Time and Cost.

BACKGROUND: Tutorial assistance is related to extra time and cost, and the hospitals' financial compensation for this activity is under debate. We therefore aimed at quantifying the extra time and resulting cost required to train one surgical resident in the operating theatre for board certification in Switzerland as an example of a training curriculum involving several surgical subspecialties. Additionally, we intended to quantify the percentage of tutorial assistance. METHODS: We analysed 200,700 operations carried out between 2008 and 2012. Median duration of procedure categories was calculated according to four different seniority levels. The extra time if the procedure was performed by residents, and resulting cost were analysed. The percentage of procedures carried out by residents as compared to more experienced surgeons was assessed over time. RESULTS: On average, residents performed about a third of all operations including typical teaching procedures like appendectomies. An increase in duration and cost of well-defined procedures categories, e.g. cholecystectomies was demonstrated if a resident performed the procedure. In less well-defined categories, residents seemed to perform less difficult procedures than senior consultants resulting in shorter durations of surgery. CONCLUSIONS: The financial impact of tutorial assistance is important, and solutions need to be found to compensate for this activity. The low percentage of procedures performed by trainees may make it difficult to fulfil requirements for board certification within a reasonable period of time. This should be addressed within the training curriculum.

Gastrojejunal Anastomosis Complications and Their Management after Laparoscopic Roux-en-Y Gastric Bypass.

BACKGROUND: Complications at the gastrojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass (LRYGB) are challenging in terms of diagnosis, therapy, and prevention. This study aims at identifying these complications and discussing their management. METHODS: Data of 228 patients who underwent a LRYGB between October 2008 and December 2011 were reviewed retrospectively to evaluate the frequency and treatment of complications such as stenoses, marginal ulcers, perforated marginal ulcers, or anastomotic leaks related to the operation. RESULTS: Follow-up information was available for 209 patients (91.7%) with a median follow-up of 38 months (range 24-62 months). Of these patients 16 patients (7.7%) experienced complications at the gastrojejunostomy. Four patients (1.9%) had stenoses and 12 patients (5.7%) marginal ulcers, one of them with perforation (0.5%). No anastomotic leaks were reported. One case with perforated ulcer and one with recurrent ulcers required surgical revision. CONCLUSION: Gastrojejunal anastomotic complications are frequent and occur within the first few days or up to several years after surgery. Stenoses or marginal ulcers are usually successfully treated nonoperatively. Laparoscopic repair, meanwhile, is an appropriate therapeutic option for perforated ulcers.

Impact of tutorial assistance in laparoscopic sigmoidectomy for acute recurrent diverticulitis.

PURPOSE: Adequate training and close supervision by an experienced surgeon are crucial to assure the patient safety during laparoscopic training. This study evaluated the impact of tutorial assistance on the duration of surgery and postoperative complications after laparoscopic sigmoidectomy. METHODS: The data from 235 patients undergoing laparoscopic sigmoidectomy were collected. Operating surgeons were classified as either residents/registrars (group A, tutorial assistance) or consultants operating autonomously (group B). Groups were compared concerning the duration of surgery and in-hospital complications using a multivariable regression model accounting for the most relevant confounders. RESULTS: The median duration of the operation in group A (n = 75) was 221 min, and that in group B (n = 160) 189 min (p < 0.001). The risk of developing any in-hospital complication (Clavien-Dindo classification I-V) was 36.0 % in Group A and 32.5 % in group B (95 % CI -16.6, 9.6 %). The risk of developing moderate to severe surgical complications (Clavien-Dindo classification II-V) was 16.0 % in group A and 12.5 % in group B (95 % CI -13.3, 6.3 %). CONCLUSIONS: We were unable to demonstrate a clear impact of tutorial assistance on the risk of postoperative complications. Although associated with a longer duration of surgery, laparoscopic sigmoidectomy for acute recurrent sigmoid diverticulitis conducted by a junior supervised surgeon appears to be a safe surgical modality.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

BACKGROUND: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. METHODS: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. RESULTS: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). CONCLUSIONS: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Factors influencing the success of in vivo sentinel lymph node procedure in colon cancer patients: Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer.

BACKGROUND: The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients. METHODS: One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed. RESULTS: Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050). CONCLUSIONS: The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

BACKGROUND: A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases. METHODS: In total, 313 lymph nodes from 22 consecutive patients with stage I, II, and III colon cancer were assessed. Half of each lymph node was analyzed initially by H&E followed by an intensive histologic workup (5 levels of H&E and immunohistochemistry analyses, the gold standard for the assessment of sensitivity/specificity of OSNA), and the other half was analyzed using OSNA. RESULTS: OSNA was more sensitive in detecting small lymph node tumor infiltrates compared with H&E (11 results were OSNA positive/H&E negative). Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity, and a concordance rate of 97.1%. OSNA resulted in an upstaging of 2 of 13 patients (15.3%) with lymph node-negative colon cancer after standard H&E examination. CONCLUSIONS: OSNA appeared to be a powerful and promising molecular tool for the detection of lymph node metastases in patients with colon cancer. OSNA had similar performance in the detection of lymph node metastases compared with intensive histopathologic investigations and appeared to be superior to standard histology with H&E. Most important, the authors concluded that OSNA may lead to a potential upstaging of >15% of patients with colon cancer.

Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer.

BACKGROUND: The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure. METHODS: One hundred seventy-four consecutive colon cancer patients were enrolled onto this prospective trial. They underwent an intraoperative SLN procedure with isosulfan blue 1% injected peritumorally followed by open standard colon resection with oncologic lymphadenectomy. Three levels of each SLN were stained with hematoxylin and eosin (H&E) and immunostained with the pancytokeratin marker AE1/AE3 if H&E was negative. RESULTS: SLN identification rate and accuracy were 89.1% and 83.9%, respectively. SLN were significantly more likely to contain tumor infiltrates than non-SLN (P < 0.001). Both SLN identification rate (P = 0.021) and the sensitivity of the procedure (P = 0.043) significantly improved with experience. The use of immunohistochemistry in SLN resulted in an upstaging of 15.4% (16 of 104) stage I and II patients considered node-negative in initial H&E analysis. CONCLUSIONS: The SLN procedure for colon cancer has good identification and accuracy rates, which further improve with increasing experience. Most importantly, the SLN procedure results in upstaging of >15% of node-negative patients. The potential advantage of performing the SLN procedure appears to be particularly important in these patients because they may potentially benefit from adjuvant therapy.

Surgical treatment of acute recurrent diverticulitis: early elective or late elective surgery. An analysis of 237 patients.

BACKGROUND: The optimal timing of elective surgery in diverticulitis remains unclear. We attempted to investigate early elective versus late elective laparoscopic surgery in acute recurrent diverticulitis in a retrospective study. METHOD: Data of patients undergoing elective laparoscopic surgery for diverticulitis were retrospectively gathered, including Hinchey stages I-II a/b. the primary endpoint was in-hospital complications according to the Clavien-Dindo classification. Secondary endpoints were surgical complications, operative time, conversion rate, and length of hospital stay. RESULTS: Of 237 patients, 81 (34%) underwent early elective operation (group A) and 156 (66%) underwent late elective operation (group B). In-hospital complications developed in 32% in group A and in 34% in group B (risk difference 2%, 95% Confidence Interval (95% CI): -11%, 14%). Higher age (p = 0.048) and borderline higher American Society of Anesthesiologists score (p = 0.056) were risk factors for in-hospital complications. Severe surgical complications occurred in 9% of patients in group A and 10% in group B (risk difference 2%, 95% CI: -6%, 9%). Conversion rate was 9% in group A and 3% in group B (p = 0.070). Severity of disease did not seem to have an impact on complications or length of hospital stay. The median postoperative hospital stay was 8 days in both groups (interquartile range 6-10). Mean operative time was 220 min (SD 64) in group A and 202 min (SD 48) in group B. CONCLUSIONS: This is the first study comparing early versus late elective surgery for diverticulitis in terms of the postoperative outcome using a validated classification. Although the retrospective setting and large confidence intervals don't allow definitive recommendations, these results are of utmost importance for the design of future prospective, randomized controlled trials.

Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients.

The prognostic value of sentinel lymph node (SLN) micro-metastases and the question whether patients with SLN micro-metastases should undergo axillary lymph node dissection remain a matter of great debate. Based on the current literature and on our own data, we provide suggestive evidence that SLN micro-metastases in early stage breast cancer patients appear to have prognostic value and should impact the decision-making regarding adjuvant therapy, however, do not necessarily require further surgical treatment.

Inadequate quality of surveillance after curative surgery for colon cancer.

BACKGROUND: Colon cancer patients are at risk for recurrence. Recurrent disease might be curable if detected early by surveillance. However, data on the quality of surveillance are scarce. The objective of this study is to analyze the quality of surveillance after curative surgery for colon cancer among a cohort of Swiss patients. PATIENTS AND METHODS: After curative surgery, 129 stage I-III colon cancer patients were followed by chart review, questionnaires, and phone interviews. National surveillance guidelines mandate periodic measurement of carcinoembryonic antigen (CEA) levels, abdominal ultrasound or computed tomography (US/CT), and colonoscopy. However, surveillance was left to the discretion of the treating physicians. Actual surveillance was compared with the recommendations in the guidelines. RESULTS: Datasets of all 129 patients were available. Median follow-up was 33.5 months (range 5.6-74.7 months). Eighteen patients (14.0%) recurred during follow-up. Three-year overall and disease-free survival were 94.7% and 83.5%, respectively. Periodic CEA measurements, US/CT, and colonoscopies as recommended by the guidelines were performed in 32.8%, 31.7%, and 23.8% of patients, respectively. Forty-four patients (34.1%) received adjuvant chemotherapy. For these patients there was a trend towards better compliance with national surveillance guidelines than for patients without adjuvant chemotherapy. CONCLUSIONS: The quality of surveillance after curative surgery for colon cancer among a cohort of Swiss patients is inadequate. Further education of health care professionals and patients regarding the potential life-saving benefits of surveillance is imperative. It is cardinal that quality of surveillance is critically analyzed in other countries with different health care systems as well.

Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study.

OBJECTIVES: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate. METHODS: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 ≤ 3 cm, cN0 M0) between 1998 and 2002. The SLN were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry. None of the patients with negative SLN or SLN micrometastases (International Union Against Cancer classification, >0.2 to ≤ 2 mm) underwent a completion ALND or radiation to the axilla. Long-term overall and disease-free survivals were compared between patients with negative SLN and those with SLN micrometastases by log rank tests. RESULTS: The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median followup of 77 months (range, 24-106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = 0.656), locoregional (P = 0.174), and axillary and distant disease-free survival (P = 0.15) between patients with negative SLN and SLN micrometastases. CONCLUSIONS: This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.

Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study.

OBJECTIVES: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate. METHODS: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 .2 mm to

Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study.

OBJECTIVE: To assess the accuracy of sentinel lymph node (SLN) frozen section in a prospective multicenter study of early-stage breast cancer patients. SUMMARY BACKGROUND DATA: The decision to perform an immediate completion axillary node dissection (ALND) is based on results of SLN frozen section. However, SLN frozen sections are not routinely performed in all centers. Moreover, the accuracy of SLN frozen section remains a matter of great debate. METHODS: Prospective multicenter trial analyzing 659 early stage breast cancer patients (pT1 and pT2

Sudden death after open gastric bypass surgery.

PURPOSE: Gastric bypass surgery has become a relatively low-risk bariatric surgical intervention in a high-risk patient population (Nguyen et al., Arch Surg, 141:445-449, 2006; Buchwald et al. JAMA, 13:1724-1737, 2004). Surgical interventions in patients suffering from morbid obesity are typically associated with excess morbidity (Parikh et al., Am Surg, 73:959-962, 2007). Though overall mortality after bariatric surgery is <1% is low (Mason et al., Obes Surg, 17:9-14, 2007), some surgical complications such as anastomotic leaks, staple line disruption and bowel obstruction may still impact on postoperative outcome (Parikh et al., Am Surg, 73:959-962, 2007; Mason et al., Obes Surg, 17:9-14, 2007). Early symptoms are often missed, as clinical presentation may be discreet, inexistent or falsely attributed to obesity. METHODS: This case report refers to a patient in whom discomfort and agitation associated with a rise in temperature heralded a fulminant septic shock syndrome precipitating his death. Literature on early complications and management after gastric bypass is reviewed. CONCLUSION: A high level of suspicion should be present in the case of an unexpected postoperative deterioration of the patient's general condition. Time to treat may be very short (Mason et al., Obes Surg, 17:9-14, 2007). Computed tomography is mandatory to rule out pulmonary embolism and bypass obstruction.

[Follow-up recommendations for patients after curative treatment of invasive breast cancer]. / Nachsorge-Empfehlungen für Patientinnen mit kurativ therapiertem, invasivem Mammakarzinom.

Oncologic follow-up and surveillance after curative therapy for invasive breast cancer serves as a quality control of the primary treatment results, enables the early diagnosis and immediate treatment in case of recurrent disease, the detection and therapy of treatment-related side effects and late sequelae, and finally includes the psychologic support of tumor-free patients over decades, during which they are at risk for recurrent disease.

Gastric necrosis complicating lately a Nissen fundoplication. Report of a case.

BACKGROUND: Gastric necrosis after Nissen fundoplication is a rare and life-threatening complication described in paediatric surgery and in some experimental models. Prompt diagnosis and appropriate therapy of acute gastric dilatation is mandatory to avoid potentially fatal gastric necrosis. CASE REPORT: This case report is the first one to describe a gastric necrosis in an adult as a late and very severe complication after Nissen fundoplication. Gastric dilatation and subsequent necrosis occurred 14 years after Nissen fundoplication because of small bowel obstruction based on adhesions. CONCLUSION: Early diagnosis and treatment of gastric dilatation after Nissen fundoplication are essential to prevent from severe secondary complications but can be difficult to establish because of atypical symptoms.

[Breast cancer surgery]. / Chirurgie du cancer du sein.

Breast conserving surgery followed by radiation therapy is the treatment of choice for early breast cancer. For patients who choice or need a mastectomy, breast reconstruction provides an acceptable alternative. Breast cancer surgery has been evolving through minimally invasive approaches. Sentinel node biopsy has already remplaced axillary lymph node dissection in the evaluation of the axilla. Local ablation of the tumor may be a valuable alternative to surgery in the future.