Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions.

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.

Evaluating the Impact of Enhanced Recovery After Surgery Protocols on Surgical Outcomes Following Bariatric Surgery-A Systematic Review and Meta-analysis of Randomised Clinical Trials.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes are evidence-based care improvement processes for surgical patients, which are designed to decrease the impact the anticipated negative physiological cascades following surgery. AIM: To perform a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the impact of ERAS protocols on outcomes following bariatric surgery compared to standard care (SC). METHODS: A systematic review was performed in accordance with PRISMA guidelines. Meta-analysis was performed using Review Manager version 5.4 RESULTS: Six RCTs including 740 patients were included. The mean age was 40.2 years, and mean body mass index was 44.1 kg/m2. Overall, 54.1% underwent Roux-en-Y gastric bypass surgery (400/740) and 45.9% sleeve gastrectomy (340/700). Overall, patients randomised to ERAS programmes had a significant reduction in nausea and vomiting (odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, P = 0.040), intraoperative time (mean difference (MD): 5.40, 95% CI: 3.05-7.77, P < 0.001), time to mobilisation (MD: - 7.78, 95% CI: - 5.46 to - 2.10, P < 0.001), intensive care unit stay (ICUS) (MD: 0.70, 95% CI: 0.13-1.27, P = 0.020), total hospital stay (THS) (MD: - 0.42, 95% CI: - 0.69 to - 0.16, P = 0.002), and functional hospital stay (FHS) (MD: - 0.60, 95% CI: - 0.98 to - 0.22, P = 0.002) compared to those who received SC. CONCLUSION: ERAS programmes reduce postoperative nausea and vomiting, intraoperative time, time to mobilisation, ICUS, THS, and FHS compared to those who received SC. Accordingly, ERAS should be implemented, where feasible, for patients indicated to undergo bariatric surgery. Trial registration International Prospective Register of Systematic Reviews (PROSPERO - CRD42023434492.

Perceived Benefits of Bariatric Surgery: Patient Perspectives.

BACKGROUND: Obesity is a chronic and complex disease characterized by the excessive accumulation of adipose tissue, which has detrimental effects on health. Evaluating the changes in quality of life (QoL) after bariatric surgery complements the medical benefits which are documented by healthcare professionals. PURPOSE: To study the perceived health benefits 1 year after substantial weight loss induced by bariatric surgery. METHODS: This pilot study evaluated patients 1 year after bariatric surgery using 13 questions related to the health domains of the KOSS: airway, body mass, cardiovascular risk, diabetes, economic impact, functional, gonadal impact, health status perceived, image, junction of the gastro-esophagus, kidney, liver, and medication. In addition, the patients were asked to score the most significant benefit as "1," while the least beneficial benefit was scored as "13." RESULTS: One hundred fourteen consecutive patients were evaluated (men = 37 and women = 77). The responses were divided into functional, metabolic, and mental/social benefits. Patients ranked the functional question, "I became more active, and I can do more things" as the most important (average score of 3.7 ± 0.2), followed by a question related to metabolic status: "I am less worried about my risk of heart disease" (4.5 ± 0.3), and then a social/mental question, "My clothes fit better" (5.4 ± 0.3). The three least valuable benefits for the cohort were sexual life improvements (8.9 ± 0.3), heartburn improvements (9.0 ± 0.3), and urinary incontinence improvements (9.8 ± 0.3). CONCLUSIONS: Our observational pilot study demonstrated that patients value functional benefits after substantial weight loss the most, but that metabolic benefits and social/mental health benefits are also considered important.

Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity-a Systematic Review and Meta-analysis of Registry Data.

PURPOSE: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data. MATERIALS AND METHODS: A systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny. RESULTS: Data from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36-0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336-0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307-0.763) were less likely to develop CRC than unoperated patients. CONCLUSION: At a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk. PROSPERO REGISTRATION: CRD42022313280.

Evaluating the Role of Circulating MicroRNAs in Predicting Long-Term Survival Outcomes in Breast Cancer: A Prospective, Multicenter Clinical Trial.

BACKGROUND: While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis. STUDY DESIGN: This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3. RESULTS: A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival. CONCLUSIONS: ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials.

Obesity and outcomes in trauma - a systematic review and meta-analysis.

BACKGROUND: The physiological abnormalities relating to obesity and metabolic syndrome can contribute to worse outcomes following trauma especially in class 2 and 3 obesity. The aim of this systematic review was to determine whether patients with a higher class of obesity who suffer traumatic injury have a higher risk of worse outcomes including in-hospital mortality than normal-weight patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science and CINAHL was performed for studies that reported a comparison of in-hospital obesity-related outcomes against normal-weight individuals aged 15 years and older following trauma. Single or multiple injuries from either blunt and/or penetrating trauma were included. Burn-related injuries, isolated head injury and studies focusing on orthopaedic related perioperative complications were excluded. RESULTS: The search yielded 7405 articles; 26 were included in this systematic review. 945,511 patients had a BMI>30. A random-effects meta-analysis was performed for analysis of all four outcomes. Patients with class 3 obesity (BMI>40) have significantly higher odds of in-hospital mortality than normal-BMI individuals following blunt and penetrating trauma (OR, 1.75; 95% CI, 1.39-2.19, p=<0.00001), significantly longer hospital LOS (SMD, 0.23; 95% CI, 0.21-0.25; p<0.00001) and significantly longer ICU LOS (SMD, 0.19; 95% CI, 0.12-0.26; p<0.0001). In contrast, studies that examined blunt and penetrating trauma and classified obesity with a threshold of BMI>30 found no significant difference in the odds of in-hospital mortality (OR, 0.94; 95% CI, 0.86-1.02, p=0.13). CONCLUSIONS: There is a higher risk of in-hospital mortality in patients living with class 3 obesity following trauma when compared with individuals with normal BMI. The management of patients with obesity is complex and trauma systems should develop specific weight related pathways to manage and anticipate the complications that arise in these patients. Systematic review registration number PROSPERO registration: CRD42021234482 Level of Evidence: Level 3.

Evaluating the Role of Circulating MicroRNAs to Aid Therapeutic Decision Making for Neoadjuvant Chemotherapy in Breast Cancer: A Prospective, Multicenter Clinical Trial.

OBJECTIVE: To evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients. INTRODUCTION: Deciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while "responders" should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC. METHODS: This prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3. RESULTS: A total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC ( P =0.049), while decreased miR-145 predicted response to NAC in HER2+ ( P =0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR ( P =0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ ( P =0.027). CONCLUSIONS: This study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.

Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity.

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.

The impact of ursodeoxycholic acid on gallstone disease after bariatric surgery: a meta-analysis of randomized control trials.

BACKGROUND: Ursodeoxycholic acid (UDCA) is a bile acid that has been shown to reduce the formation of gallstones after significant weight loss. OBJECTIVE: This study aimed to evaluate the impact of UDCA on the incidence of gallstones after bariatric surgery. SETTINGS: An electronic search of PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), Scopus (Elsevier) databases, EMBASE, CINAHL, Clinicaltrials.gov, and Web of Science. METHODS: A meta-analysis of randomized control trials was performed. The primary outcome was the incidence of gallstones after bariatric surgery. Secondary outcomes included type of operation and time interval to and characteristics associated with gallstone formation. RESULTS: Ten randomized control trials including 2583 patients were included, 1772 patients (68.6%) receiving UDCA and 811 (31.4%) receiving placebo. There was a significant reduction in gallstone formation in patients who received UDCA postoperatively (risk ratio [RR] .36, 95% confidence interval [CI] .22-.41, P < .00001). The overall prevalence of gallstone formation was 24.7% in the control group compared to 7.3% in the UDCA group. A dose of ≤600 mg/day had a significantly reduced risk of gallstone formation compared to the placebo group (risk ratio .35; 95% CI .24-.53; P < .001). The risk reduction was not significant for the higher dose (>600 mg/day) group (risk ratio .30; 95% CI, .09-1.01, P = .05). CONCLUSIONS: UDCA significantly reduces the risk of both asymptomatic and symptomatic gallstones after bariatric surgery. A dose of 600 mg/day is associated with improved compliance and better outcomes regardless of type of surgery. UDCA should be considered part of a standard postoperative care bundle after bariatric surgery.

Assessment of baseline rates of functional and absolute iron deficiency in bariatric surgery candidates: a retrospective study.

BACKGROUND: Preoperative optimization of iron status is a priority in candidates for bariatric surgery. Inflammation is strongly associated with obesity, and as a consequence, functional iron deficiency (ID) is potentially an underreported issue in surgical candidates. OBJECTIVES: In light of updated practice guidelines, to retrospectively review preoperative iron status in an Irish cohort of bariatric surgery candidates, taking account of the relative incidence rate of functional ID. SETTING: A tertiary care obesity service with bariatric surgery referral in Ireland. METHODS: Baseline nutritional biochemistry records were reviewed between February 2017 and February 2020 in a hospital, Dublin, Ireland. Absolute ID was defined as serum ferritin <30 µg/L; functional ID was defined as ferritin, 30 to 100 µg/L, in the presence of C-reactive protein >5 mg/L. Anemia was indexed with reference to hemoglobin and qualified by vitamin B12 and folate status to rule out anemia unrelated to primary ID. RESULTS: The analysis included 120 patients, 68% female, 49.6 ± 9.3 years, and body mass index, 52.0 ± 9.6 kg/m2. The prevalence of absolute and functional ID was 11.7% and 30.8%, respectively (P = .0003). Anemia was associated with absolute ID and functional ID in 14.3% and 10.8% of patients (P = .29). Folate and vitamin B12 deficiency occurred in <5% of patients. CONCLUSION: In patients seeking bariatric surgery for severe obesity, the prevalence of baseline functional ID is substantial and can be associated with anemia. These findings raise queries with regard to how best to optimize preoperative iron status in the context of ongoing inflammation.

Enhanced Recovery After Bariatric Surgery: Feasibility and Outcomes in a National Bariatric Centre.

PURPOSE: This study aimed to assess outcomes of bariatric surgical procedures after the implementation of an enhanced recovery after bariatric surgery protocol in the National Bariatric Centre in Ireland. MATERIALS AND METHODS: Data on consecutive bariatric procedures performed over a 36-month period was prospectively recorded. ERABS interventions utilized included preoperative counselling, shortened preoperative fasts, specific anaesthetic protocols, early postop mobilization and feeding, and extended post-discharge thromboprophylaxis. RESULTS: A total of 280 primary bariatric procedures were performed over a 36-month period. The primary procedures were laparoscopic sleeve gastrectomy (57.5%), laparoscopic one anastomosis gastric bypass (33.2%) and laparoscopic Roux-en-Y gastric bypass (9.3%). Mean (SD) age was 48 (± 10) years, mean (SD) preoperative BMI 49.5 (± 9) kg/m2 and 68% were female. Median ASA score was 3, and median OSMRS also 3. Over 50% of patients had a diagnosis of hypertension or OSA, and over one-third had a diagnosis of type 2 diabetes mellitus or dyslipidemia. All procedures were completed laparoscopically and 29 patients underwent a simultaneous procedure. The mean (SD) length of stay was 2.3 (± 1.4) days (median 2 days, range 2-47 days). Overall postoperative morbidity rate was 10.0% (n = 29). The 30-day readmission and reoperation rates were 3.6% and 2.5% respectively. There was no mortality recorded in this series. CONCLUSION: Implementing an ERABS protocol was feasible, safe, associated with low morbidity, no mortality, acceptable LOS and low readmission and reoperation rates. Although patients with obesity have a spectrum of disease-related complications, this should not preclude the use of an ERABS protocol in bariatric surgery.

Segmental versus extended colectomy for tumours of the transverse colon: a systematic review and meta-analysis.

AIM: There is no consensus on the appropriate extent of oncological resection for tumours of the transverse colon. Concerns regarding tumour factors such as pattern of lymph node spread and technical factors such as anastomotic perfusion lead to a variety of procedures being performed. METHODS: A comprehensive search for published studies examining outcomes following segmental versus extended colectomy for transverse colon tumours was performed adhering to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Random effects methods were used to combine data. RESULTS: Seven comparative series examining outcomes in 3395 patients were identified. Segmental colectomy results in shorter operating times (mean difference 15.80 min, 95% CI -20.98 to -10.62, P < 0.001) and less ileus (OR 0.52, 95% CI 0.33-0.81, P = 0.004). There was no difference in length of hospital stay (mean difference 1.53 days, 95% CI -3.79 to 0.73, P = 0.18). Extended colectomy results in a lower rate of anastomotic leak (OR 0.62, 95% CI 0.40-0.97, P = 0.04). There are fewer nodes retrieved in segmental colectomy (mean difference 7.60 nodes, 95% CI -9.60 to -5.61, P < 0.001) but no difference in disease recurrence (OR 0.88, 95% CI 0.59-1.34, P = 0.56) or overall survival (OR 0.98, 95% CI 0.68-1.4, P = 0.9). CONCLUSIONS: Available data are limited due to a lack of randomized controlled trials. However, based on current evidence, segmental resection for transverse colon tumours is associated with less ileus but lower lymph node yields and higher anastomotic leak rates. Length of stay is similar. Oncological outcomes are equivalent.

Neoadjuvant Chemoradiotherapy and Liver Transplantation for Unresectable Hilar Cholangiocarcinoma: The Irish Experience of the Mayo Protocol.

BACKGROUND: Pioneered by the Mayo Clinic, multimodal therapy with neoadjuvant chemoradiotherapy and orthotopic liver transplant has emerged as a promising option for unresectable hilar cholangiocarcinoma (hCCA). This study reports the experience of the Irish National Liver Transplant Programme with the Mayo Protocol. METHODS: All patients diagnosed with unresectable hCCA between 2004 and 2016, who were eligible for the treatment protocol, were prospectively studied. RESULTS: Thirty-seven patients commenced chemoradiotherapy. Of those, 11 were excluded due to disease progression and 26 proceeded to liver transplantation. There were 24 males, the median age was 49, and 88% had underlying primary sclerosing cholangitis. R0 and pathologic complete response rates were 96% and 62%, respectively. Overall median survival was 53 months and 1-, 3-, and 5-year survival was 81%, 69%, and 55%, respectively. The median survival of patients achieving a pathologic complete response was 83.8 months compared with 20.9 months in the group with residual disease (P = 0.036). Six patients (23%) developed disease recurrence. Among the patients who developed metastatic disease during neoadjuvant treatment, median survival was 10.5 months compared with 53 months in patients who proceeded to transplant (P < 0.001). CONCLUSIONS: Neoadjuvant chemoradiotherapy followed by liver transplantation substantially increases the survival of patients with unresectable hCCA. Achieving a pathologic complete response confers a significant survival benefit.

The changing cost of breast cancer care: lessons from a centralised modern cancer centre.

BACKGROUND: The cost of new cancer technologies has been the subject of intense debate in recent years. There have been significant advances in therapeutic techniques for breast cancer over the past 20 years. This has been accompanied by the concentration of services in designated cancer centres. The aim of this study was to examine the changing cost of breast cancer management over an 18-year period and identify factors underlying this. METHODS: We use breast cancer services data from Galway University Hospital in 1995-1996, 2005-2006 and 2011-2012 to examine the changing pattern of care costs and survival. RESULTS: The number of patients treated for breast cancer rose from 200 in 1995-1996, to 411 in 2005-2006 and 563 in 2011-2012. Two-year survival rose in line with national figures from 84 to 89.78 and 92.07%, in the three-time periods respectively. Adjusting for inflation, the average cost per patient rose from €14,710 (95% C.I., €13,398 to €16,022) in 1995-1996 to €30,405 (95% C.I., €38,620 to €32,189) in 2005-2006, before falling to €14,458 (C.I., €13,343 to €15,572) in 2011-2012. We found significant changes in the pattern of costs, with some rising in relative and absolute terms while others fell as new therapies became available and/or moved off patent. CONCLUSION: Within an evolving context where services are centralised, new therapies emerge and subsequently come off patent, our understanding of the value of cancer therapies continues to evolve. This has important implications for the evaluation of new therapies and broader policy initiatives in this area.

Bariatric Surgery for Obesity.

In this review, the authors discuss the indications for and the published outcomes of commonly performed bariatric procedures, including weight loss, perioperative morbidity and mortality, late complications, as well as the impact of bariatric surgery on comorbidities, cardiovascular risk, and mortality. They also briefly discuss the mechanisms by which bariatric/metabolic surgery causes such significant weight loss and health gain.

Can CT-PET and Endoscopic Assessment Post-Neoadjuvant Chemoradiotherapy Predict Residual Disease in Esophageal Cancer?

OBJECTIVE: The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiotherapy (nCRT) in predicting complete pathologic response (pCR) in locally advanced esophageal cancer (LAEC). DESIGN: A prospective cohort study. BACKGROUND: nCRT is increasingly standard of care in LAEC, with pCR a surrogate for excellent outcome. Predicting pCR before surgery, with metabolic imaging and endoscopy, may spare patients' operative intervention. METHODS: One hundred thirty-eight consecutive patients [mean age 61 ±â€Š8, 99 male (72%), 103 (75%) adenocarcinoma] underwent nCRT with CT-PET and endoscopy 4 to 6 weeks later, and surgery subsequently. A complete metabolic response (cMR) was defined as SUVmax of <4. A complete endoscopic response (cER) was no residual mucosal abnormality. The association of pCR with cMR and cER was analyzed. RESULTS: pCR was achieved in 30 patients (22%); 37% SCC and 17% adenocarcinoma. A cMR was evident in 63 (46%), of whom 17 (27%) had a pCR and 17(27%) were ypN+. A cER was observed in 45 (33%). The Spearman correlation for cER and cMR was 0.066 (P = 0.479), for cER and pCR was 0.004 (P = 0.969), and cMR and pCR -0.120 (P = 0.160). The sensitivity, specificity, positive predictive value, and negative predictive value of cMR was 57%, 57%, 27%, and 82%, respectively, and for combined cMR and cER was 24%, 83%, 28%, and 79%, respectively. CONCLUSIONS: The prediction of pCR through CT-PET and endoscopy independently or combined is limited by low sensitivity and poor positive predictive value. Protocols to avoid surgery in patients with apparent complete clinical complete based on these criteria should be adopted with considerable caution.