Extended lymph node resection versus standard resection for pancreatic and periampullary adenocarcinoma

BACKGROUND Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins. OBJECTIVES To compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures. SEARCH METHODS We searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions. SELECTION CRITERIA Randomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed-effect model in the absence of substantial heterogeneity (I² 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes. MAIN RESULTS We included seven studies with 843 participants (421 ELA and 422 SLA). All seven studies included Kaplan-Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) -3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low-quality evidence). There was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low-quality evidence). Operating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001). There may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02). There may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001). There was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low-quality evidence). AUTHORS' CONCLUSIONS There is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas

Mucosal Monosaccharide Transporter Expression in Newborns With Jejunoileal Atresia and Along the Adult Intestine

OBJECTIVES: In newborn rodents, intestinal maturation involves delayed fructose transporter GLUT5 expression until weaning. In jejunoileal atresia (JIA), distal intestinal segments lack exposure to amniotic fluid-containing carbohydrates. We assessed in human newborns, the impact of intestinal maturation and obstruction on mucosal monosaccharide transporter expression. METHODS: Samples were obtained from 10 newborns operated for small intestinal atresia and from 17 adults undergoing gastroduodenoscopy and/or ileocolonoscopy. mRNA expression of the transporters SGLT1, GLUT1, GLUT2, GLUT5, and GLUT7 was measured in neonate samples proximal and distal of the atresia as well as in adult duodenum, ileum, and colon. Protein expression and localization was assessed using immunofluorescence. RESULTS: Although mRNA expression of monosaccharide transporters did not significantly differ between newborn and adult samples, luminal fructose transporter GLUT5 protein was absent in 0- to 4-day-old neonates, but expressed in adults. The mRNA expression of the 5 tested monosaccharide transporters was unchanged distal from the JIA relative to proximal. Similarly, luminal sodium-dependent glucose transporter SGLT1 and basolateral GLUT2 were expressed proximal and distal to JIA as visualized by immunofluorescence staining. With the exception of glucose transporter GLUT1 that showed highest expression levels in colon, all investigated hexose transporters showed strongest expression in duodenum, lower levels in ileum and lowest in colon. CONCLUSIONS: Human newborns lack small intestinal fructose transporter GLUT5 protein expression and small intestinal atresia does not affect the expression of hexose transporters

Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use

L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases. Citrullinated histones, however, may even predict a worse outcome in cancer patients. Supplementation of citrulline is better tolerated compared to arginine and might be useful to slightly improve muscle strength or protein balance. The following article shall provide an overview of L-citrulline properties and functions, as well as the current evidence for its use as a biomarker or as a therapeutic supplement

Treatment Strategies for Pilonidal Sinus Disease in Switzerland and Austria

Background and objective: No current nationwide consensus exists on pilonidal disease (PD) treatment in Switzerland and Austria. The objective of this study was to assess and compare the spectrum of PD treatment strategies in Switzerland and Austria. Materials and Methods: A survey including 196 certified institutions (Switzerland, N = 99 and Austria, N = 97) was performed. Treatment strategies for both chronic and acute pilonidal disease were investigated, as well as evolution of treatment over the last 20 years. Results: In total, 92 of 196 (47%) hospitals participated in the survey. Recurrence rate (20%) was similar between the two countries. In acute pilonidal disease, a two-stage approach with incision and drainage as the first step was preferred over a one-stage procedure in both countries. In Austria, all patients with chronic pilonidal disease were treated as inpatients, whereas 28% of patients in Switzerland were treated on an outpatient basis (p = 0.0019). Median length of hospital stay was double in Austria (four days) compared to Switzerland (two days; p < 0.001). Primary resection and off-midline closure (p = 0.017) and the use of tissue flaps (p = 0.023) were performed more commonly in Austria than in Switzerland. Minimally invasive techniques were performed more often in Switzerland than in Austria (52% vs. 4%, p < 0.001). Overall, wide excision with secondary wound healing or midline closures declined over the last 20 years. Conclusion: Treatment strategies for chronic PD differ between Austria and Switzerland with more and longer inpatient care in Austria, increasingly minimally invasive approaches in Switzerland, and outdated procedures still being performed in both countries. Overall, heterogeneity of practice dominates in both countries

Open versus laparoscopic pyloromyotomy for pyloric stenosis.

BACKGROUND Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young children (aged one year or less) and can be treated by laparoscopic (LP) or open (OP) longitudinal myotomy of the pylorus. Since the first description in 1990, LP is being performed more often worldwide. OBJECTIVES To compare the efficacy and safety of open versus laparoscopic pyloromyotomy for IHPS. SEARCH METHODS We conducted a literature search on 04 February 2021 to identify all randomised controlled trials (RCTs), without any language restrictions. We searched the following electronic databases: MEDLINE (1990 to February 2021), Embase (1990 to February 2021), and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the Internet using the Google Search engine (www.google.com) and Google Scholar (scholar.google.com) to identify grey literature not indexed in databases. SELECTION CRITERIA We included RCTs and quasi-randomised trials comparing LP with OP for hypertrophic pyloric stenosis. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from trial reports. Where outcomes or study details were not reported, we requested missing data from the corresponding authors of the primary RCTs. We used a random-effects model to calculate risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. Two review authors independently assessed risks of bias. We used GRADE to assess the certainty of the evidence for all outcomes. MAIN RESULTS The electronic database search resulted in a total of 434 records. After de-duplication, we screened 410 independent publications, and ultimately included seven RCTs (reported in 8 reports) in quantitative analysis. The seven included RCTs enrolled 720 participants (357 with open pyloromyotomy and 363 with laparoscopic pyloromyotomy). One study was a multi-country trial, three were carried out in the USA, and one study each was carried out in France, Japan, and Bangladesh. The evidence suggests that LP may result in a small increase in mucosal perforation compared with OP (RR 1.60, 95% CI 0.49 to 5.26; 7 studies, 720 participants; low-certainty evidence). LP may result in up to 5 extra instances of mucosal perforation per 1,000 participants; however, the confidence interval ranges from 4 fewer to 44 more per 1,000 participants. Four RCTs with 502 participants reported on incomplete pyloromyotomy. They indicate that LP may increase the risk of incomplete pyloromyotomy compared with OP, but the confidence interval crosses the line of no effect (RR 7.37, 95% CI 0.92 to 59.11; 4 studies, 502 participants; low-certainty evidence). In the LP groups, 6 cases of incomplete pyloromyotomy were reported in 247 participants while no cases of incomplete pyloromyotomy were reported in the OP groups (from 255 participants). All included studies (720 participants) reported on postoperative wound infections or abscess formations. The evidence is very uncertain about the effect of LP on postoperative wound infection or abscess formation compared with OP (RR 0.59, 95% CI 0.24 to 1.45; 7 studies, 720 participants; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on postoperative incisional hernia compared with OP (RR 1.01, 95% CI 0.11 to 9.53; 4 studies, 382 participants; very low-certainty evidence). Length of hospital stay was assessed by five RCTs, including 562 participants. The evidence is very uncertain about the effect of LP compared to OP (mean difference -3.01 hours, 95% CI -8.39 to 2.37 hours; very low-certainty evidence). Time to full feeds was assessed by six studies, including 622 participants. The evidence is very uncertain about the effect of LP on time to full feeds compared with OP (mean difference -5.86 hours, 95% CI -15.95 to 4.24 hours; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on operating time compared with OP (mean difference 0.53 minutes, 95% CI -3.53 to 4.59 minutes; 6 studies, 622 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Laparoscopic pyloromyotomy may result in a small increase in mucosal perforation when compared with open pyloromyotomy for IHPS. There may be an increased risk of incomplete pyloromyotomy following LP compared with OP, but the effect estimate is imprecise and includes the possibility of no difference. We do not know about the effect of LP compared with OP on the need for re-operation, postoperative wound infections or abscess formation, postoperative haematoma or seroma formation, incisional hernia occurrence, length of postoperative stay, time to full feeds, or operating time because the certainty of the evidence was very low for these outcomes. We downgraded the certainty of the evidence for most outcomes due to limitations in the study design (most outcomes were susceptible to detection bias) and imprecision. There is limited evidence available comparing LP with OP for IHPS. The included studies did not provide sufficient information to determine the effect of training, experience, or surgeon preferences on the outcomes assessed

Intestinal IMINO transporter SIT1 is not expressed in human newborns

The expression of amino acid transporters in small intestine epithelium of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino- and amino acid transporter SIT1 (SLC6A20) was approximately 3-fold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared to adults. At the protein level, the major luminal neutral amino acid transporter BAT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 (ACE2) were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nontheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression

Plasma citrulline correlates with basolateral amino acid transporter LAT4 expression in human small intestine

Background & aims Plasma citrulline, a non-protein amino acid, is a biochemical marker of small intestine enterocyte mass in humans. Indeed, citrulline is highly correlated with residual bowel length in patients with short bowel syndrome. It is known to be synthesised in epithelial cells of the small intestine from other amino acids (precursors). Citrulline is then released into systemic circulation and interconverted into arginine in kidneys. If plasma citrulline concentration depends on abundance of intestinal amino acid transporters is not known. The aim of the present study was to explore whether plasma citrulline concentration correlates with the expression of intestinal amino acid transporters. Furthermore, we assessed if arginine in urine correlates with plasma citrulline. Methods Duodenal samples, blood plasma and urine were collected from 43 subjects undergoing routine gastroduodenoscopy. mRNA expression of seven basolateral membrane amino acid transporters/transporter subunits were assessed by real-time PCR. Plasma and urine amino acid concentrations of citrulline, its precursors and other amino acids were analysed using High Performance Liquid Chromatography measurements. Amino acid transporter mRNA expression was correlated with blood plasma and urine levels of citrulline and its precursors using Spearman's rank correlation. Likewise, urine arginine was correlated with plasma citrulline. Results Plasma citrulline correlated with the mRNA expression of basolateral amino acid transporter LAT4 (Spearman's r = 0.467, p = 0.028) in small intestine. None of the other basolateral membrane transporters/transporter subunits assessed correlated with plasma citrulline. Plasma citrulline correlated with urinary arginine, (Spearman's r = 0.419, p = 0.017), but not with urinary citrulline or other proteinogenic amino acids in the urine. Conclusions In this study, we showed for the first time that small intestinal basolateral LAT4 expression correlates with plasma citrulline concentration. This finding indicates that LAT4 has an important function in mediating citrulline efflux from enterocytes. Furthermore, urine arginine correlated with plasma citrulline, indicating arginine in the urine as possible additional marker for small intestine enterocyte mass. Finally, basolateral LAT4 expression along the human small intestine was shown for the first time