Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

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

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

Role of lymphadenectomy in resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) remains one of the most devastating malignant diseases, predicted to become the second leading cause of cancer-related death by 2030. Despite advances in surgical techniques and in systemic therapy, the 5-year relative survival remains a grim 9% for all stages combined. The extent of lymphadenectomy has been discussed intensively for decades, given that even in early stages of PC, lymph node (LN) metastasis can be detected in approximately 80%. PURPOSE: The primary objective of this review was to provide an overview of the current literature evaluating the role of lymphadenectomy in resected PC. For this, we evaluated randomized controlled studies (RCTs) assessing the impact of extent of lymphadenectomy on OS and studies evaluating the prognostic impact of anatomical site of LN metastasis and the impact of the number of resected LNs on OS. CONCLUSIONS: Lymphadenectomy plays an essential part in the multimodal treatment algorithm of PC and is an additional therapeutic tool to increase the chance for surgical radicality and to ensure correct staging for optimal oncological therapy. Based on the literature from the last decades, standard lymphadenectomy with resection of at least ≥ 15 LNs is associated with an acceptable postoperative complication risk and should be recommended to obtain local radicality and accurate staging of the disease. Although radical surgery including appropriate lymphadenectomy of regional LNs remains the only chance for long-term tumor control, future studies specifically assessing the impact of neoadjuvant therapy on extraregional LNs are warranted.

Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer-a distinct view on lymph node yield.

PURPOSE: While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS: The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS: A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION: While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.

4/5 Gastrectomy in Patients Undergoing Pancreaticoduodenectomy Reduces Delayed Gastric Emptying.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD), impairing oral food intake and reducing the quality of life. The aim of this study was to investigate the effect of 4/5 gastrectomy on DGE after PD. MATERIALS AND METHODS: Patients undergoing pylorus-preserving PD (ppPD) were compared with PD with 4/5 subtotal gastrectomy, including resection of the gastric fundus (SGPD). The primary endpoint was DGE, according to the International Study Group of Pancreatic Surgery definition. Secondary outcomes included time to solid food intake, time to first flatus, postoperative morbidity, and body weight change 6- and 12-wk after surgery. RESULTS: Sixty patients underwent either ppPD (n = 32) or SGPD (n = 28). Patient characteristics were well balanced between the groups. DGE occurred in 47% after ppPD and 18% after SGPD (P = 0.027). Compared with ppPD, time to solid food intake and time to first flatus were significantly shorter after SGPD (8 d [interquartile range 5-12] versus 5 d [4-6]; P = 0.003 and 5 d [4-7] versus 3 d [2-5]; P = 0.001, respectively). Major postoperative morbidity and hospital stay was similar between the groups. Weight loss at 6 wk was less pronounced after ppPD (-4.8% [-6.3 to -2.7] versus -7.5% [-8.9 to -5.9]; P = 0.013), however, comparable after 3 and 6 mo (ppPD -7.6% [-8.5 to -4.8] versus SGPD -8.4% [-17.3 to -5.2]; P = 0.334 and ppPD -6.0% [-14.5 to 6.0] versus SGPD -9.5% [-11.8 to -7.0], P = 0.414, respectively). CONCLUSIONS: Compared with pylorus preservation, 4/5 gastrectomy significantly reduced the frequency of DGE and led to a faster gastrointestinal passage after PD. However, the benefits of a reduced DGE rate and a faster gastrointestinal passage should be carefully balanced against an increased weight loss after 4/5 gastrectomy in the early postoperative phase.

Posterior enucleation of the pancreatic head: an alternative route of access for parenchyma-sparing pancreatic resection.

BACKGROUND: Enucleation has become an alternative treatment in benign or low-malignant cystic tumors, including intraductal papillary mucinous neoplasms (IPMN). For enucleation to be a safe alternative to the standard procedures, there must be good access to the resection area. In this report, we present such a route for dorsally situated IPMNs. METHODS: The head of the pancreas was exposed by an extended Kocher maneuver to the left lateral edge of the aorta. Stay sutures were placed along the second part of the duodenum to allow maximal rotation of the pancreatic head to the left, which exposed the posterior aspect of the pancreatic head. The cystic lesion was then enucleated followed by a protective pancreaticojejunostomy on the resection cavity. RESULTS: Two consecutive patients with IPMNs of the dorsal pancreatic head successfully underwent dorsal enucleation. The postoperative course was uneventful in the first patient, while the course of the second patient was complicated by a clinically relevant pancreatic fistula, delayed gastric emptying, and hospital discharge on day 35. CONCLUSION: This study shows the feasibility of a dorsal approach to the pancreatic head for enucleation as well as reconstruction by means of posterior Roux-en-Y pancreaticojejunostomy. In very selected cases in specialized centers, cystic lesions in the posterior aspect of the pancreatic head will become amenable to enucleation with preservation of pancreatic functionality. However, more research is needed to clarify postoperative outcomes of this approach.

Short- versus long-term complementary nutritional support via needle catheter jejunostomy after pancreaticoduodenectomy: Study protocol of a randomized controlled trial.

INTRODUCTION: Pancreatic resection is the only curative treatment for pancreatic cancer. Due to tumor cachexia most patients present with a weight loss at the time of diagnosis. Postoperatively the weight loss is often intensified. Tumor cachexia has an influence on the post-operative morbidity and mortality and on the overall survival. Complementary nutrition has a benefit on the mentioned issues. Needle catheter jejunostomy (NCJ) offers a well-tolerated and safe way for additional nutrition therapy. Until today, the optimal length of postoperative supplementary nutrition has not been evaluated. METHODS AND ANALYSIS: The study is designed as a randomized controlled trial to compare the effect of complementary nutritional support until discharge and until 8-weeks after discharge for patients after pancreaticoduodenectomy (PD). The primary endpoint is the comprehensive complications index assessed 12 weeks postoperatively. The grading of the complications will be performed by a blinded assessor. The secondary endpoints are: quality of life, a nutritional assessment and the assessment of the effect on adjuvant therapies and 5-year survival. Follow-up visits are planned 1-, 3-, 6-, 12- and 60 month postoperatively. A total sample size of 140 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat principle. ETHICS AND DISSEMINATION: The ethics committee of the University of Bern reviewed and approved this study on 22.08.2016 (KEK BE 322/14). The trial was registered in the German Clinical Trial Register (DRKS00010237) on 25.08 2016. The present trial is the first study comparing short- and long-term complementary nutritional support after PD in randomized controlled study. The results will allow a postoperative nutritional therapy after PD based on high quality data. The results will be presented at relevant surgical conferences and written publications of the short-term results and long-term oncologic results are planned within surgical journals.

Case-matched study of lesser versus greater curvature approach in laparoscopic Warshaw pancreatectomy.

BACKGROUND: In laparoscopic distal pancreatectomy (LapDP), the pancreas is accessed in a greater curvature approach (GCA). The lesser curvature approach (LCA) has been proposed in underweight patients. The study investigated the feasibility of LCA irrespective of the body mass index (BMI). METHODS: This retrospective study included consecutive patients scheduled to undergo LapDP with the LCA. A matched cohort (1:1) underwent GCA. Spleen preservation was performed using the Warshaw technique. Splenic perfusion was intraoperatively assessed by indocyanine green (ICG) angiography. RESULTS: The LCA with LapDP was successful in 12/15 patients. In 2 cases, LCA had to be converted to GCA and in 1 patient to open surgery. The cohorts were well matched in sex (P = 1.0), age (P = .67), indication (P = 1.0), and median BMI (23.4 kg/m2 vs 24.8 kg/m2, P = .41). Splenic preservation was achieved in 14/15 patients with LCA and 4/15 patients with GCA (P = .33). In all LCA cases, ICG angiography indicated sufficient spleen perfusion. The groups had similar morbidity (P = 1.0) and hospital stay (P = .74). CONCLUSIONS: LCA was feasible in 80% irrespective of BMI and provided an excellent field of exposure. ICG angiography was feasible in the Warshaw technique. Its reliability should be evaluated in prospective studies.

Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged, thereby leading to increased cost. A recent randomized controlled trial showed that the consumption of regular black coffee after colectomy is associated with a significantly faster resumption of intestinal motility. The mechanism by which coffee stimulates intestinal motility is unknown, but caffeine seems to be the most likely stimulating agent. Thus, the effect of caffeine on postoperative bowel activity after colon surgery will be analyzed in this trial, herein referred to as CaCo. METHODS/DESIGN: Patients scheduled for elective laparoscopic colectomy or upper rectum resection are eligible to participate in this double-blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion criteria will be allocated after the surgical procedure to one of three treatment arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will take the capsules containing the study medication three times daily with a meal. The primary endpoint of the study is the time to a solid bowel movement. The study treatment will be stopped after the patient produces a solid bowel movement or has taken ten capsules, whichever occurs first. To determine the colonic passage time, patients will take a capsule with radiopaque markers at breakfast for the first 3 days after surgery. On the fourth day, the location of the markers will be determined with an abdominal X-ray scan. Further secondary objectives are the postoperative morbidity and mortality, well-being, sleeping behavior, and length of hospital stay. The study size was calculated to be 180 patients with an interim analysis occurring after 60 patients. DISCUSSION: From a previous study investigating coffee, evidence exists that caffeine might have a positive influence on the postoperative bowel activity. This double-blinded, placebo-controlled, randomized trial tries to show that caffeine will shorten the postoperative bowel paralysis and, thus, will improve recovery and shorten the hospital stay after colon surgery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02510911 Swiss National Clinical Trials Portal SNCTP000001131.

Patients with Adenocarcinoma of the Small Intestine with 9 or More Regional Lymph Nodes Retrieved Have a Higher Rate of Positive Lymph Nodes and Improved Survival.

PURPOSE: To assess the influence of regional lymph node (RLN) retrieval on stage migration of adenocarcinoma of the small intestine and survival. PATIENTS AND METHODS: From the Surveillance, Epidemiology, and End Results database,1090 patients with nonmetastatic small bowel adenocarcinoma were identified in between 2004 and 2011. The impact of the number of RLNs removed on histopathological staging and oncological outcome was assessed utilizing Cox proportional hazard regression models with and without risk-adjustment, propensity score methods, and joinpoint regression analysis. RESULTS: The rate of node-positive cancer increased steadily with the number of retrieved RLNs up to 9 RLNs, which suggests that a minimum of 9 (95 % CI 5.5­10.5) retrieved RLNs are needed for the detection of node-positive disease (P < 0.001). From 657 of 1090 patients (60.3 %), 9 or more RLNs were retrieved. While in 2004 only in 46.0 % of all cases 9+ RLNs were retrieved, this rate increased to 69.3 % in 2011 (P < 0.001). The multivariable analysis demonstrated that the retrieval of 9+ RLNs was associated with better overall (hazard ratio of death [HR] = 0.67, 95 % CI 0.55­0.82, P < 0.001) and cancer-specific survival (HR = 0.77, 95 % CI 0.61­0.96, P = 0.022). This finding was confirmed by a propensity score-adjusted analysis, which indicated increased overall (HR = 0.67, 95 % CI 0.50­0.89, P < 0.001) and cancer-specific survival (HR = 0.67, 95 % CI 0.49­0.92, P = 0.013) in patients with the retrieval of 9+ RLNs. CONCLUSION: To our knowledge, this is the first population-based propensity score-adjusted investigation in small bowel adenocarcinoma. A sufficient number of RLNs should be retrieved to achieve an optimal oncological outcome

Survival after renal cell carcinoma metastasis to the thyroid: single center experience and systematic review of the literature.

BACKGROUND: Renal cell carcinoma can metastasize to uncommon sites, for example, the thyroid gland where metastases are rarely found. To determine the patient survival and the time between cancer diagnosis and thyroid metastasis, we analyzed a large patient cohort from our hospital records and performed a systematic review. PATIENTS AND METHODS: Patients diagnosed between 1978 and 2007 with thyroid metastases from renal cell carcinoma were retrospectively identified from the hospital database. A systematic literature search was performed for publications describing at least three cases of thyroid metastasis from renal cell carcinoma. Case data from the identified studies were collected and used to determine the survival data. RESULTS: We identified 34 patients (19 females) from our hospital records with a mean age of 67 years (range, 33-79) when thyroid metastasis was diagnosed. Median time to primary metastasis after resection of renal cell carcinoma was 6.5 years (range, 0-25) with a single case of synchronous metastasis. Median survival after primary metastasis was 4.7 years (95% confidence interval [CI]: 1.8-7.6). The systematic review included 32 studies with 285 patients. Case data could be extracted for 202 patients. Median time to thyroid metastasis (without synchronous cases) was 8.8 years (95% CI: 7.5-10.1). Median actuarial survival after thyroid metastasis was 3.4 years (95% CI: 2.2-4.6). Total thyroidectomy was not associated with a better survival compared to partial thyroidectomies. CONCLUSIONS: Time to thyroid metastasis of renal cell carcinoma can be very long, and survival after thyroidectomy is favorable compared to metastasis to other sites.

Baseline mortality-adjusted survival in resected rectal cancer patients.

BACKGROUND: This investigation assessed the baseline mortality-adjusted 5-year survival after open rectal cancer resection. METHODS: The 5-year survival rate was analyzed in 885 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 2002 and 2011 using risk-adjusted Cox proportional hazards regression models adjusted for population-based baseline mortality. RESULTS: The 5-year relative and overall survival rates were 80.9%(95% confidence interval (CI): 77.0-85.0%) and 71.9%(95% CI, 68.4-75.5%), respectively. The 5-year relative survival rates for stage I, II, III, and IV cancer were 97.8% (95% CI, 93.1-102.8%), 90.9%(95% CI, 84.3-98.1%), 72.0% (95% CI, 64.7-80.1%), and 24.4% (95% CI: 16.0-37.0%), respectively. After the curative resection of stage I-III rectal cancer, fewer than every other observed death was cancer-related. The 5-year relative survival rate for stage I cancer did not differ from the matched average national baseline mortality rate (P = 0.419). Higher age (hazard ratio (HR) 0.94, 95% CI: 0.92-0.95, P < 0.001) was protective for relative survival but unfavorable for overall survival (HR 1.04, 95% CI: 1.02-1.05, P < 0.001). Female gender was only unfavorable for relative survival (HR 1.59, 95% CI: 1.11-2.29, P = 0.014). CONCLUSION: The analysis of relative survival in a large cohort of rectal cancer patients revealed that stage I rectal cancer is fully curable. The findings regarding age and gender may explain the conflicting results obtained to date from studies based on overall survival.

Use of human fibrin glue (Tisseel) versus staples for mesh fixation in laparoscopic transabdominal preperitoneal hernioplasty (TISTA): a randomized controlled trial (NCT01641718).

BACKGROUND: Inguinal hernia repair is one of the most common surgical procedures worldwide. This procedure is increasingly performed with endoscopic techniques (laparoscopy). Many surgeons prefer to cover the hernia gap with a mesh to prevent recurrence. The mesh must be fixed tightly, but without tension. During laparoscopic surgery, the mesh is generally fixed with staples or tissue glue. However, staples often cause pain at the staple sites, and they can cause scarring of the abdominal wall, which can lead to chronic pain. We designed a trial that aims to determine whether mesh fixation with glue might cause less postoperative pain than fixation with staples during a transabdominal preperitoneal patch plastic repair. METHODS/DESIGN: The TISTA trial is a prospective, randomized, controlled, single-center trial with a two-by-two parallel design. All patients and outcome-assessors will be blinded to treatment allocations. For eligibility, patients must be male, ≥18 years old, and scheduled for laparoscopic repair of a primary inguinal hernia. One group comprises patients with a unilateral inguinal hernia that will be randomized to receive mesh fixation with either tissue glue or staples. The second group comprises patients with bilateral inguinal hernias. They will be randomized to receive mesh fixation with tissue glue either on the right or the left side and with staples on the other side. The primary endpoint will be pain under physical stress, measured at 24 h after surgery. Pain will be rated by the patient based on a numeric rating scale from 0 to 10, where 10 equals the worst pain imaginable. A total of 82 patients will be recruited (58 patients with unilateral inguinal hernias and 24 patients with bilateral hernias). This number is estimated to provide 90% power for detecting a pain reduction of one point on a numeric rating scale, with a standard deviation of one. DISCUSSION: Patients with bilateral hernias will receive two meshes, one fixed with glue, and the other fixed with staples. This design will eliminate the inter-individual bias inherent in comparing pain measurements between two groups of patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01641718.

Allogeneic blood transfusion does not affect outcome after curative resection for advanced cholangiocarcinoma.

PURPOSE: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. METHODS: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. RESULTS: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. CONCLUSIONS: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.

Perioperative blood transfusions do not impact overall and disease-free survival after curative rectal cancer resection: a propensity score analysis.

OBJECTIVE: To assess the putative impact of perioperative blood transfusions on overall and disease-free survival in patients undergoing curative resection of stage I-III rectal cancer by applying propensity-scoring methods. BACKGROUND: Whether perioperative blood transfusions negatively impact survival remains a matter of great debate. METHODS: In a single-center study, 401 patients undergoing open curative resection of stage I-III rectal cancer between 1996 and 2008 were assessed. The median follow-up was 34.2 months. Patients who did and did not receive perioperative blood transfusions were compared using Cox regression and propensity score analyses. RESULTS: Overall, 217 patients (54.1%) received blood transfusions. Patients' characteristics were highly biased concerning transfusions (propensity score 0.77±0.23 vs. 0.28±0.25; P<0.001). In unadjusted analysis, blood transfusions were associated with a 119% increased risk of mortality [hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.34-3.57, P=0.001]. In propensity score-adjusted Cox regression (HR: 1.02, 95% CI: 0.65-1.58, P=0.970), blood transfusions did not increase the risk of overall survival. Similarly, in propensity score-adjusted Cox regression (HR: 0.86, 95% CI: 0.60-1.23, P=0.672), blood transfusions were not associated with an increased risk of recurrence. CONCLUSIONS: This is the first propensity score-based analysis providing compelling evidence that worse oncological outcomes after curative rectal cancer resection in patients receiving perioperative blood transfusions are caused by the clinical circumstances requiring transfusions, not due to the blood transfusions themselves. Therefore, concerns about overall and disease-free survival should be no issue in the decision-making regarding perioperative blood transfusions in patients undergoing curative rectal cancer resection.

IPMN: surgical treatment.

PURPOSE: Cystic pancreatic tumors are being detected more frequently, and particularly, intraductal papillary mucinous neoplasia (IPMN) has recently attracted increased attention. The detection rate of IPMN has increased over the last decade; however, management of this neoplasm remains controversial. METHODS: Based on a review of the relevant literature and the international guidelines, we discuss the diagnostic evaluation of IPMN, its treatment, and prognosis. RESULTS: While IPMN represents only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. It may not be possible to differentiate main duct disease from branch duct disease (MD-IPMN vs. BD-IPMN) prior to surgery. This distinction has not only an impact on treatment but also on prognosis, as MD-IPMN is more often malignant. IPMN has updated consensus guideline indications for conservative and surgical resection. CONCLUSIONS: Since patients with IPMN of the pancreas are at risk of developing recurrent IPMN and pancreatic ductal adenocarcinoma in the remnant pancreas and extrapancreatic malignancies, early recognition, treatment, and systemic surveillance are of great importance. No conclusions can be drawn from the available evidence with respect to the efficacy of surveillance and follow-up treatment programs. A better understanding of the natural course of IPMN and the biology of pancreatic cancer is mandatory to enable further diagnostic and treatment improvements.

Study protocol for a randomized, double-blind, placebo-controlled trial of a single preoperative steroid dose to prevent nausea and vomiting after thyroidectomy: the tPONV study.

BACKGROUND: Postoperative nausea and vomiting after general anesthesia is not only an unpleasant problem affecting 20-30% of surgical patients but may also lead to severe postoperative complications. There is a particularly high incidence of postoperative nausea and vomiting following thyroidectomy. Dexamethasone has been described as highly effective against chemotherapy-induced nausea and vomiting and has been proposed as a first-line method of postoperative nausea and vomiting prophylaxis. Despite this possible beneficial effect, the prophylactic administration of dexamethasone before surgery to prevent or ameliorate postoperative nausea and vomiting has not been established. A bilateral superficial cervical plexus block during thyroid surgery under general anesthesia significantly reduces pain. Of even greater clinical importance, this block prevents the need for postoperative opioids. Therefore, patients undergoing thyroidectomy and a bilateral superficial cervical plexus block are an ideal group to investigate the efficacy of dexamethasone for postoperative nausea and vomiting. These patients have a high incidence of postoperative nausea and vomiting and do not require opioids. They have no abdominal surgery, which can cause nausea and vomiting via a paralytic ileus. Combined with the highly standardized anesthesia protocol in use at our institution, this setting allows all known biases to be controlled. METHODS/DESIGN: We will perform a parallel two-arm, randomized (1:1), double-blind, placebo-controlled, single-center trial. Adults (≥18 years) scheduled for primary partial or total thyroidectomy because of a benign disease will be eligible for inclusion. The participants will be randomized to receive a single, intravenous preoperative dose of either 8 mg of dexamethasone in 2 ml saline (treatment group) or saline alone (placebo group). All the patients will receive a bilateral superficial cervical plexus block and standardized anesthesia. The primary outcome will be the incidence of postoperative nausea and vomiting. A total of 152 patients will be recruited, providing 80% power to detect a 50% reduction in the incidence of postoperative nausea and vomiting. Any patients who require opioid treatment will be excluded from the per-protocol analysis. DISCUSSION: In the present protocol, we reduced bias to the greatest extent possible. Thus, we expect to definitively clarify the efficacy of dexamethasone for postoperative nausea and vomiting prophylaxis. TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT01189292.

Blood transfusion does not adversely affect survival after elective colon cancer resection: a propensity score analysis.

PURPOSE: The aim of this study was to assess the putative impact of perioperative blood transfusions on overall survival in patients undergoing curative resection for stage III colon cancer by applying propensity scoring methods. METHODS: In a single-center study, a total of 309 patients who underwent open curative resection for stages I-III colon cancer from 1996-2008 were assessed. The mean follow-up period was 47 ± 38 months. Transfused and non-transfused patients were compared using both Cox regression and propensity score analyses. RESULTS: Overall, 148 patients (47.9 %) received blood transfusions. The patient characteristics were highly biased toward transfusions (propensity score 0.68 ± 0.22 vs. 0.30 ± 0.22, p <0.001). In the unadjusted analysis, blood transfusions were associated with a 90 % increased risk of overall mortality (hazard ratio 1.90, 95 % CI: 1.19-3.04, p = 0.001). The 5-year survival for patients receiving blood transfusions was 64.5 % (95 % CI: 56.0-74.3 %) compared with 80.1 % (95 % CI: 72.8-88.2 %) in those not receiving blood transfusions. In the propensity score-adjusted Cox regression analysis (hazard ratio: 0.85, 95 % CI = 0.53-1.37, p = 0.501), blood transfusions did not increase the risk of overall mortality. After risk adjustment, the 5-year survival rate for patients receiving blood transfusions was 66.6 % (95 % CI: 57.4-77.3 %) compared with 61.8 % (95 % CI: 51.9-73.7 %) for those who did not. CONCLUSION: This study is the first propensity score-based analysis that provides evidence that poor oncological outcomes after curative colon cancer resection in patients receiving perioperative blood transfusions are due to the clinical circumstances that require the transfusions and are not due to the blood transfusions.

A rapid and accurate new bedside test to assess maximal liver function: a case report.

BACKGROUND: In liver surgery, appropriate preoperative evaluation and preparation of the patient is of cardinal importance. The up-to-date, preoperative prediction of residual liver function has thus far been limited. As post-hepatectomy liver failure is a major cause of mortality, a new and simple bedside test (LiMAx) has been developed to predict postoperative liver function in conjunction with preoperative volumetric analysis of the liver. CASE PRESENTATION: A 45-year-old patient presented with a cecal carcinoma and a large synchronous liver metastasis for major liver surgery. Liver function was determined by the LiMAx-test for the enzymatic capacity of cytochrome P450 1A2, which is ubiquitously and solely active in the liver. A solution of 2 mg/kg body weight (13)C-labeled methacetin was injected as a bolus into an intravenous catheter and, thereafter, was metabolized into acetaminophen and (13)CO2 and pulmonarily exhaled. The analysis of the (13)CO2/(12)CO2 ratio was performed using online breath sampling over a period of maximally 60 minutes. Based on this test, a value of more than 315 µg/kg/h represents normal liver function. A laparoscopic right hemihepatectomy was planned during virtual resection with a residual liver volume of 48% and a preoperative anticipated residual LiMAx of 301 µg/kg/h. After successful resection, the initial postoperative LiMAx value was 316 µg/kg/h, indicating good liver function and a correct prediction of the outcome. CONCLUSION: In the presented patient, residual liver function could be accurately predicted preoperatively using a combination of the new LiMax test with CT-volumetry. This test might significantly improve preoperative evaluation and postoperative outcomes in liver surgery.