Efficacy of intraoperative cholangiography versus preoperative magnetic resonance cholangiography in patients with intermediate risk for common bile duct stones.

BACKGROUND: This is the first randomized trial to evaluate the efficacy of intraoperative cholangiography (IOC) and magnetic resonance cholangiopancreatography (MRCP) in patients with suspected CBDS. METHODS: This unblinded, multicenter RCT was conducted at five swiss hospitals. Eligibility criteria were suspected CBDS. Patients were randomized to IOC and laparoscopic cholecystectomy (LC), followed by endoscopic retrograde cholangiopancreatography (ERCP) if needed, or MRCP followed by ERCP if needed, and LC. Primary outcome was length of stay (LOS), secondary outcomes were cost, stone detection, and complication rates. RESULTS: 122 Patients were randomised to the IOC Group (63) or the MRCP group (59). Median LOS for the IOC and the MRCP groups were 4 days IQR [3, 6] and [4, 6], with an estimated increase of LOS of 1.2 days in the MRCP group (p = 0.0799) in the linear model. Median cost in the IOC and MRCP groups were 10 473 Swiss Francs (CHF) and 10 801 CHF, respectively (p = 0.694). CBDS were found in 24 and 12 patients in the IOC and the MRCP groups, respectively (p = 0.0387). The complication rate did not differ between both groups. CONCLUSION: There is equipoise between both pathways. IOC has a significantly higher diagnostic yield than MRCP. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02351492: Radiological Investigation of Bile Duct Obstruction (RIBO).

Laparoscopic liver resection: a single-centre experience.

BACKGROUND: The past 25 years have seen the increased use of minimally invasive surgery. The development of these techniques has impacted the domain of liver surgery. This study aimed to describe the safety, feasibility, benefits and results of laparoscopic liver resection in a single tertiary care centre. METHODS: We reviewed the medical records of all patients who underwent liver surgery between January 2005 and December 2016 at the University Hospital of Basel. We selected all liver resections performed by laparoscopic surgery. To evaluate the results of the laparoscopic liver surgery, we chose the following data: the conversion rate from laparoscopy to open surgery, the median operating time, postoperative complications, the median length of stay following surgery and the median surgical margin in patients with malignant lesions. RESULTS: Of the 274 liver operations, 201 (73%) were performed by open surgery and 73 (27%) by laparoscopy. Sixty-nine laparoscopic liver resections were included in this study. The selected laparoscopic liver resections were performed in 65 patients: 38 men and 27 women. The median age was 59 (range 29–85) years. Forty resections were performed for malignant lesions and 29 (42%) for benign diseases. The median operating time was 112 (range 50–247) minutes. The conversion rate was 19%. The most common cause for conversion was bleeding (69% of all conversions, 13% of all patients). Postoperative complications occurred in 15 patients (22%). The median hospitalisation time was 7.1 (range 2–23) days. Thirty-two patients (46.5% of all patients) had hepatocellular carcinoma. The mean tumour size was 25.6 (range 5–55) mm. The median surgical margin was 9 mm. CONCLUSION: This study showed that in our centre laparoscopic liver surgery is a safe and effective treatment option for both benign and malignant liver lesions.

Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis.

Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (r s = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (r s = 0.435, P = 0.0003, and r s = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments.

Longterm outcome of anal fistula - A retrospective study.

This retrospective observational study analyses the outcomes of patients undergoing surgery for anal fistula at a single centre in order to assess recurrence and re-operation rates after different surgical techniques. During January 2005 and May 2013, all patients with anal fistula were included. Baseline characteristics, details of presentation, fistula anatomy, type of surgery, post-surgical outcomes and follow-up data were collected. The primary endpoints were long-term closure rate and recurrence rate after 2 years. Secondary endpoints were persistent pain, postoperative complications and continence status. A total of 65 patients were included. From a total amount of 93 operations, 65 were fistulotomies, 13 mucosal advancement flaps, 7 anal fistula plugs and 8 cutting-setons. The mean follow up was 80 months. Healing was achieved in 85%. The highest recurrence rate was seen in anal fistula plug with 42%. On the other hand, no recurrence was observed in the cutting-seton procedures. For all included operation no persistent postoperative pain nor incontinence was observed. In conclusion, despite all existing anal fistula operations up to date, the optimal technique with low recurrence rate and assured safety for the anal sphincter is still lacking. Nonetheless, according to our promising results for the cutting-seton technique, this technique, otherwise considered obsolete, should be further evaluated in a prospective study.

The role of CRP and Pentraxin 3 in the prediction of systemic inflammatory response syndrome and death in acute pancreatitis.

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.

Secondary hyperparathyroidism: recurrence after total parathyroidectomy with autotransplantation.

BACKGROUND: Secondary hyperparathyroidism (sHPTH) is common in patients with end-stage chronic kidney disease. If drug therapy fails, total parathyroidectomy with autotransplantation of parathyroid tissue into the forearm (PTX-AT) is the most widely used procedure. High recurrence rates of sHPTH following PTX-AT are reported in the literature. OBJECTIVE: The aim of this study was to evaluate recurrences of sHPTH following PTX-AT in detail in order to develop strategies to prevent recurrences in the future. METHODS: This retrospective study analysed a single-centre cohort of 42 patients who underwent PTX-AT for sHPTH at a tertiary centre in Switzerland. Postoperative PTH levels were evaluated to determine the recurrence and persistence rates and the time to recurrence. Furthermore, the peri- and postoperative outcomes were assessed. Patients on dialysis and patients with a functioning kidney transplant suffering tertiary HPTH were analysed separately. RESULTS: Intraoperative measurements showed that serum PTH decreased to 6.9% (3.3–15.0%) of the preoperative baseline level. After a median follow-up of 89.5 months (IQR 31.9–152.9), persistence of sHPTH was found in five patients (11.9%) and recurrence in four patients (9.5%), giving a total recurrence rate of 21.4%. CONCLUSION: Recurrence of sHPTH after PTX remains a problem, occurring in every fifth patient. In our experience, the introduction of intraoperative PTH measurement has helped to lower the rates of persistence and recurrence. Further reductions in the recurrence rate might be achieved with novel, more accurate pre- and intraoperative imaging techniques.

Surgical repair of an esophageal perforation after radiofrequency catheter ablation for atrial fibrillation.

Recent reports have described the incidence of atrioesophageal fistulas (AEF), often resulting in death, from radiofrequency (RF) catheter ablation of atrial fibrillation (AF).1 Cases of esophageal perforation without concomitant AEF have not been described as extensively.1 The precise mechanisms leading to esophageal injury after catheter ablation without involvement of the left atrium are not fully understood. The surgical approach to treat esophageal perforation is strongly recommended.2 However, a unified surgical treatment approach has not yet been established. We describe a case of successful surgical repair of an esophageal perforation after ablation using surgical repair in combination with an omental wrap.

Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor-Based 3D Culture System.

Colorectal cancer (CRC) is a leading cause of cancer-related death. Conventional chemotherapeutic regimens have limited success rates, and a major challenge for the development of novel therapies is the lack of adequate in vitro models. Nonmalignant mesenchymal and immune cells of the tumor microenvironment (TME) are known to critically affect CRC progression and drug responsiveness. However, tumor drug sensitivity is still evaluated on systems, such as cell monolayers, spheroids, or tumor xenografts, which typically neglect the original TME. Here, it is investigated whether a bioreactor-based 3D culture system can preserve the main TME cellular components in primary CRC samples. Freshly excised CRC fragments are inserted between two collagen scaffolds in a "sandwich-like" format and cultured under static or perfused conditions up to 3 d. Perfused cultures maintain tumor tissue architecture and densities of proliferating tumor cells to significantly higher extents than static cultures. Stromal and immune cells are also preserved and fully viable, as indicated by their responsiveness to microenvironmental stimuli. Importantly, perfusion-based cultures prove suitable for testing the sensitivity of primary tumor cells to chemotherapies currently in use for CRC. Perfusion-based culture of primary CRC specimens recapitulates TME key features and may allow assessment of tumor drug response in a patient-specific context.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes.

BACKGROUND: The lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN. METHODS: One hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3 months. RESULTS: Fifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8-54). DFS and OS were significantly shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and 4.5 (p = 0.054). CONCLUSIONS: LNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

Gut microbiota modulate T cell trafficking into human colorectal cancer.

OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. RESULTS: CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. CONCLUSIONS: Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues.

Cortisol Outperforms Novel Cardiovascular, Inflammatory, and Neurohumoral Biomarkers in the Prediction of Outcome in Acute Pancreatitis.

OBJECTIVES: The aims of this study were to assess whether copeptin, pro-atrial natriuretic peptide, proadrenomedullin, and cortisol are associated with disease severity in patients with acute pancreatitis (AP) and to compare their ability in predicting organ failure or death. METHODS: From April 2011 to January 2015, 142 patients with AP were included in this prospective single-center study and observed for 4 days. Disease severity was rated by the Atlanta 1992 and 2012 criteria and organ failure by the modified Marshall score. The aforementioned laboratory markers, C-reactive protein, and procalcitonin were measured. RESULTS: Patients with moderate to severe AP showed significantly higher plasma concentrations of all biomarkers than did those with mild AP. Overall, 30 organ failures or deaths occurred. All biomarkers except cortisol had only modest discriminatory ability, with areas under the receiver operating characteristic curve (AUCs) between 0.44 and 0.66. Cortisol showed an AUC of 0.78 compared with the Acute Physiology and Chronic Health Evaluation II score with an AUC of 0.75. CONCLUSIONS: Cortisol was the best predictor of organ failure or death. All biomarkers were associated with disease severity to a similar degree as C-reactive protein, the criterion-standard marker in AP. Further studies are warranted to define their clinical role.

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel.

The control of the in vivo vascularization of engineered tissue substitutes is essential in order to obtain either a rapid induction or a complete inhibition of the process (e.g. in muscles and hyaline-cartilage, respectively). Among the several polymers available, Elastin-Like Recombinamers (ELR)-based hydrogel stands out as a promising material for tissue engineering thanks to its viscoelastic properties, non-toxicity, and non-immunogenicity. In this study, we hypothesized that varying the cell adhesion properties of ELR-hydrogels could modulate the high angiogenic potential of adipose tissue-derived stromal vascular fraction (SVF) cells, predominantly composed of endothelial/mural and mesenchymal cells. Human SVF cells, embedded in RGD-REDV-bioactivated or unmodified ELR-hydrogels, were implanted in rat subcutaneous pockets either immediately or upon 5-day-culture in perfusion-bioreactors. Perfusion-based culture enhanced the endothelial cell cord-like-organization and the release of pro-angiogenic factors in functionalized constructs. While in vivo vascularization and host cell infiltration within the bioactivated gels were highly enhanced, the two processes were strongly inhibited in non-functionalized SVF-based hydrogels up to 28 days. ELR-based hydrogels showed a great potential to determine the successful integration of engineered substitutes thanks to their capacity to finely control the angiogenic/inflammation process at the recipient site, even in presence of SVF cells.

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic mini gastric bypass in the treatment of obesity: study protocol for a randomized controlled trial.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the gold standard in bariatric surgery, achieving durable long-term weight loss with improvement of obesity-related comorbidities. Lately, the laparoscopic mini gastric bypass (LMGB) has gained worldwide popularity with similar results to LRYGB in terms of weight loss and comorbidity resolution. However, there is a lack of randomized controlled trials (RCT) comparing LMGB and LRYGB. This article describes the design and protocol of a randomized controlled trial comparing the outcomes of these two bariatric procedures. METHODS/DESIGN: The trial is designed as a single center, randomized, patient and observer blinded trial. The relevant ethics committee has approved the trial protocol. To demonstrate that LMGB is not inferior to LRYGB in terms of excess weight loss (EWL) the study is conducted as a non-inferiority trial with the sample-size calculations performed accordingly. EWL 12 months after surgery is the primary endpoint, whereas 3-year EWL, morbidity, mortality, remission of obesity related comorbidities, quality of life (QOL) and hormonal and lipid profile changes are secondary endpoints. Eighty patients, 18 years or older and with a body mass index (BMI) between 35 and 50 kg/m2 who meet the Swiss guidelines for the surgical treatment of morbid obesity will be randomized. The endpoints and baseline measurements will be assessed pre-surgery, peri-surgery and post-surgery (fixed follow up measurements are at discharge and at the time points 6 weeks and 12 and 36 months postoperatively). DISCUSSION: With its 3-year follow up time, this RCT will provide important data on the impact of LMGB and LRYGB on EWL, remission of comorbidities, QOL and hormonal and lipid profile changes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02601092 . Registered on 28 September 2015.

Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial.

BACKGROUND: Based on observational studies, administration of surgical antimicrobial prophylaxis (SAP) for the prevention of surgical site infection (SSI) is recommended within 60 min before incision. However, the precise optimum timing is unknown. This trial compared early versus late administration of SAP before surgery. METHODS: In this phase 3 randomised controlled superiority trial, we included general surgery adult inpatients (age ≥18 years) at two Swiss hospitals in Basel and Aarau. Patients were randomised centrally and stratified by hospital according to a pre-existing computer-generated list in a 1:1 ratio to receive SAP early in the anaesthesia room or late in the operating room. Patients and the outcome assessment team were blinded to group assignment. SAP consisted of single-shot, intravenous infusion of 1·5 g of cefuroxime, a commonly used cephalosporin with a short half-life, over 2-5 min (combined with 500 mg metronidazole in colorectal surgery). The primary endpoint was the occurrence of SSI within 30 days of surgery. The main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01790529. FINDINGS: Between Feb 21, 2013, and Aug 3, 2015, 5580 patients were randomly assigned to receive SAP early (2798 patients) or late (2782 patients). 5175 patients (2589 in the early group and 2586 in the late group) were analysed. Median administration time was 42 min before incision in the early group (IQR 30-55) and 16 min before incision in the late group (IQR 10-25). Inpatient follow-up rate was 100% (5175 of 5175 patients); outpatient 30-day follow-up rate was 88·8% (4596 of 5175), with an overall SSI rate of 5·1% (234 of 4596). Early administration of SAP did not significantly reduce the risk of SSI compared with late administration (odds ratio 0·93, 95% CI 0·72-1·21, p=0·601). INTERPRETATION: Our findings do not support any narrowing of the 60-min window for the administration of a cephalosporin with a short half-life, thereby obviating the need for increasingly challenging SAP timing recommendations. FUNDING: Swiss National Science Foundation, Hospital of Aarau, University of Basel, Gottfried und Julia Bangerter-Rhyner Foundation, Hippocrate Foundation, and Nora van Meeuwen-Häfliger Foundation.

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.

Assessing the severity of acute pancreatitis (ASAP) in Switzerland: A nationwide survey on severity assessment in daily clinical practice.

BACKGROUND/OBJECTIVES: We aim to assess which tools for severity stratification in acute pancreatitis are used in today's daily clinical practice and to what extent the new Atlanta classification is being implemented by the medical community in Switzerland. METHODS: The heads of surgical, medical and emergency departments of Swiss hospitals (n = 83) that directly treat patients with acute pancreatitis were given access to an online survey and asked to forward the questionnaire to their team. The questionnaire consisted of 16 items, including questions about the specialty background of the participants, the allocation of patients with AP, severity assessment, patient management, the role of imaging procedures, and future perspectives. RESULTS: A total of 233 participants from 63 hospitals responded (response rate, 74%). A vast majority of participants [198 (87%)] does assess severity. The most frequently used tools are the Ranson [108 (87%)] and APACHE II scores [28 (23%)]. A majority of the participants were not satisfied with the currently available tools to assess severity [130 (59%)]. A minority [15 (12%)] use the revised Atlanta classification to assess the degree of severity in AP. CONCLUSIONS: The Ranson score remains the dominant risk stratification tool in clinical practice in Switzerland, followed by the APACHE II score. Other modern instruments, such as the Atlanta 2012 classification, have not yet earned broad recognition and have not reached daily practice. Further efforts must be made to expand physicians' awareness of their existence and significance.

The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer.

Purpose: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells.Experimental Design: CD66b+ and CD8+ cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b+ cells were evaluated by flow cytometry. CD66b+/CD8+ cells crosstalk was investigated by in vitro experiments.Results: CD66b+ cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8+ T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8+ T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8+ cell stimulation in the presence of CD66b+ cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b+ and CD8+ T lymphocytes is associated with significantly better prognosis, as compared with CD8+ T-cell infiltration alone.Conclusions: Neutrophils enhance the responsiveness of CD8+ T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8+ T cells, suggesting that they might effectively promote antitumor immunity. Clin Cancer Res; 23(14); 3847-58. ©2017 AACR.

Intraoperative Patterns of Gastric Microperfusion During Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a very popular surgical treatment for the treatment of morbidly obese patients. Staple line leaks are the major cause of severe morbidity. Reasons for leaks might be hyperpressure (mechanical theory) or hypoperfusion (vascular theory) of the narrow gastric tube. This study assessed microperfusion patterns of the stomach during LSG using visible light spectroscopy (VLS), a method to measure tissue oxygenation (saturated O2 (StO2)). METHODS: The study population comprised 20 patients undergoing LSG. Real-time intraoperative microperfusion measurements were performed at nine different ventral stomach localizations in the antrum, body, and fundus at the beginning of the operation, after mobilization of the greater curve and after sleeve resection. RESULTS: There were 17 women and 3 men, mean age 42.9 years, mean BMI 45.6 kg/m2. There were no staple line leaks. StO2% values dropped substantially in the most cephalad area of measurement at the greater curve after mobilization (56 versus 49 %) and after resection (60 versus 49.5 %). The reduction in StO2 in the most cephalad area from before mobilization of the stomach to resection was 9.5 % (p < 0.01). CONCLUSION: Assessment of microperfusion patterns of the stomach during LSG using VLS is safe and efficacious to use allowing an accurate measurement of StO2%. The upper third of the stomach is the zone of reduced microperfusion with a significant drop of tissue oxygenation after sleeve resection of the stomach.