Infected urachal cyst in an adult patient.

Urachal cyst is a clinical malformation caused by failure of the allantois to obliterate during embryological development. Because of its rare presentation in adults, urachal cysts are often incorrectly diagnosed. Delay in diagnosis can cause complications such as peritonitis, fistula, sepsis, or even malignant manifestation. We report the case of a 19-year-old adult male, who presented with clinical features mimicking appendicitis. Ultrasound and magnetic resonance imaging confirmed diagnosis of an infected urachal cyst, which was treated surgically.

Redo surgery with longitudinal resection for dilated bowel in Hirschsprung disease: an illustrative case series.

PURPOSE: Patients with Hirschsprung disease (HD) can have persistent obstructive symptoms after resection of the aganglionic segment. If obstructive symptoms are treated inadequately, this may lead to recurrent faecal stasis and impaction, and may result in severe distension of the bowel. A permanently distended bowel which not responds to conservative treatment may be an indication for redo surgery. The aim of this study is to describe our experiences and the short-term results of a novel technique: longitudinal antimesenteric resection with a longitudinal anastomosis. METHODS: We reviewed the medical records of our three patients who underwent longitudinal resection of severe distended bowel. This technique aims to improve defecation by improving faecal passage and is characterized by resection of the antimesenteric side of the distended intestinal segment, followed by plication with a longitudinal anastomosis. In this paper, this novel technique is described in detail, as well as short-term outcomes. RESULTS: All patients had an uneventful recovery after longitudinal antimesenteric resection. During follow-up, the functional outcomes were excellent, with a large improvement of bowel function. All patients were continent for faeces, and treated with low-dose laxatives or occasional preventive irrigation in one patient. There were no more complaints of persistent constipation or soiling. CONCLUSION: Longitudinal resection is a surgical redo-procedure offering large benefits for patients with Hirschsprung disease with distended bowel after primary surgery.

Robotic-Assisted Nissen Fundoplication in Pediatric Patients: A Matched Cohort Study.

BACKGROUND: Nissen Fundoplication (NF) is a frequently performed procedure in children. Robotic-assisted Nissen Fundoplication (RNF), with the utilization of the Senhance® Surgical System (SSS®) (Asensus Surgical® Inc., Durham, NC, USA) featuring 3 mm instruments, aims to improve precision and safety in pediatric surgery. This matched cohort study assesses the safety and feasibility of RNF in children using the SSS®, comparing it with Laparoscopic Nissen Fundoplication (LNF). METHODS AND RESULTS: Twenty children underwent RNF with the SSS® between 2020 to 2023 and were 1:1 matched with twenty LNF cases retrospectively selected from 2014 to 2023. Both groups were similar regarding male/female ratio, age, and weight. Two of the twenty RNF cases (10%) experienced intraoperative complications, whereas three in the LNF group of whom two required reinterventions. The observed percentage of postoperative complications was 5% in the RNF group compared to 15% in the LNF group (p = 0.625). The operative times in the RNF group significantly dropped towards the second study period (p = 0.024). CONCLUSIONS: Utilizing SSS® for NF procedures in children is safe and feasible. Observational results may tentatively suggest that growing experiences and continued development will lead to better outcomes based on more accurate and safe surgery for children.

Testicular Vascularization after Pediatric Inguinal Hernia Repair: A Systematic Review and Meta-Analysis.

BACKGROUND: The effect of pediatric inguinal hernia repair (IHR) on testicular vascularization remains unclear. Manipulating the spermatic cord during surgery may reduce blood flow due to edema and vasoconstriction. This can lead to testicular atrophy. The study aims to review current knowledge of testicular vascular impairment following IHR in children. METHODS: A systematic literature search was conducted in PubMed/Medline, Embase, Cochrane Library, and Web of Science. Methodological quality was assessed using validated tools. Data were extracted, and a pooled data analysis was performed. RESULTS: Ten studies were included in the systematic review. Six of these studies were eligible for meta-analysis. This revealed a significant decrease in testicular vascularization during the short-term follow-up (1 day-1 week) after IHR using the open surgical approach. This decrease was not present after laparoscopic intervention. There was no more increased resistance in the vessels at long-term follow-up (1 month-6 months), suggesting that the impaired vascularity is only temporary. CONCLUSIONS: There seems to be a short-term transient vascular impairment of the testis after open IHR in children. This might be of clinical relevance to prefer the laparoscopic approach for IHR in children, even though the open approach is the gold standard, in contrast to adult IHR. The impact on testicular function and sperm quality later in life remains unclear. Comparative studies of both techniques are needed to determine if there is a significant difference in testicular vascularity. Long-term studies are necessary to assess the impact of transiently reduced vascularity on sperm quality and fertility later in life.

Removal of fractured peripherally inserted central venous catheter in the leg of a neonate.

An infant with a corrected gestational age of 38 weeks, weighing 3.1 kg, was referred to our pediatric surgical department because of a fractured peripherally inserted central venous catheter in the left lower limb with the end retracting into the deep venous system. An operation was undertaken to remove the PICC. Because the central venous catheter was, unintentionally, placed in the left small saphenous vein and thus positioned in the left femoral vein, the left great saphenous vein was incised to gain access. Subsequently, the catheter could be removed successfully. Fracturing of a peripherally inserted central venous catheter is a rare occurance. Removal depends on vessel size, location and experertise.

The gut-liver axis.

PURPOSE OF REVIEW: The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic nervous system, intestinal failure and gut microbiota has been investigated in the development of hepatic, intestinal and extra-intestinal disease. RECENT FINDINGS: The autonomic nervous system can be stimulated via enteral fat leading to cholecystokinin release, stimulating receptors in the gut and in the brain. This promotes bowel integrity, dampening the inflammatory response to food antigens. Consensus exists that intravenously administered long-chain fatty acids can cause liver damage but randomized-controlled trials are lacking. Disruption of the enterohepatic circulation of bile salts can give rise to cholestasis and nonalcoholic fatty liver disease, which may progress to fibrosis and cirrhosis. Reduced intestinal availability of bile salts reduces stimulation of the farnesoid X receptor. This may induce hepatic bile salt overload and associated hepatotoxicity through reduced action of intestinal fibroblast growth factor 19. Evidence is put forward to suggest that the intestinal microbiota is associated with liver abnormalities. SUMMARY: Enteral lipids reduce inflammation and liver damage during stress or systemic inflammation, whereas parenteral lipid is associated with liver damage. Maintaining the enterohepatic circulation of bile salts limits hepatic cholestasis through an farnesoid X receptor feedback pathway. Changes in gut microbiota composition may induce liver disease.

Protocol for the development of a core outcome set for the optimisation of treatment and follow-up of patients with an anorectal malformation (ARM): The ARM and OUtcome Review (ARMOUR)-project.

BACKGROUND: Primary treatment of an anorectal malformation (ARM) is surgical restoration of the anatomy. These children can experience many problems later in life; therefore, a long-term follow-up by an experienced team is needed. The aim of the ARM and OUtcome Review (ARMOUR-study) is to identify the lifetime outcomes that are important from a medical and patients' perspective and develop a core outcome set (COS) that can be implemented in a care pathway to support individual ARM management decisions. METHODS: First, a systematic review will identify clinical and patient-reported outcomes described in studies conducted in patients with an ARM. Second, qualitative interviews with patients of different age categories and their caregivers will be held to ensure that the COS will include outcomes that are relevant from the patient's perspective. Finally, the outcomes will be taken forward to a Delphi consensus exercise. Using multiple web-based Delphi rounds, key stakeholders (medical experts, clinical researchers and patients) will prioritise outcomes. During a face-to-face consensus meeting, the final COS will be determined. These outcomes can be evaluated in a life-long care pathway for patients with ARM. DISCUSSION: The development of a COS for ARMs aims to reduce heterogeneity in outcome reporting between (clinical) studies, enhancing the availability of comparable data, which will facilitate evidence-based patient care. Assessment of the outcomes in the COS during individual care pathways for ARM can support shared decisions regarding management. The ARMOUR-project has ethical approval and is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. LEVEL OF EVIDENCE: Treatment study level II.

Total parenteral nutrition induces a shift in the Firmicutes to Bacteroidetes ratio in association with Paneth cell activation in rats.

The use of total parenteral nutrition (TPN) in the treatment of critically ill patients has been the subject of debate because it has been associated with disturbances in intestinal homeostasis. Important factors in maintaining intestinal homeostasis are the intestinal microbiota and Paneth cells, which exist in a mutually amendable relationship. We hypothesized that the disturbed intestinal homeostasis in TPN-fed individuals results from an interplay between a shift in microbiota composition and alterations in Paneth cells. We studied the microbiota composition and expression of Paneth cell antimicrobial proteins in rats receiving TPN or a control diet for 3, 7, or 14 d. qPCR analysis of DNA extracts from small intestinal luminal contents of TPN-fed rats showed a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes after 14 d (P < 0.05) compared with the control group. This finding coincided with greater staining intensity for lysozyme and significantly greater mRNA expression of the Paneth cell antimicrobial proteins lysozyme (P < 0.05), rat α-defensin 5 (P < 0.01), and rat α-defensin 8 (P < 0.01). Finally, 14 d of TPN resulted in greater circulating ileal lipid-binding protein concentrations (P < 0.05) and greater leakage of horseradish peroxidase (P < 0.01), which is indicative of enterocyte damage and a breached intestinal barrier. Our findings show a shift in intestinal microbiota in TPN-fed rats that correlated with changes in Paneth cell lysozyme expression (r(s) = -0.75, P < 0.01). Further studies that include interventions with microbiota or nutrients that modulate them may yield information on the involvement of the microbiota and Paneth cells in TPN-associated intestinal compromise.

Long-term results after restorative proctocolectomy with ileal pouch-anal anastomosis at a young age.

BACKGROUND: Restorative proctocolectomy with IPAA is an optimal surgical treatment for patients with familial adenomatous polyposis and therapy resistant ulcerative colitis, few data are available on long-term results in patients who have undergone this operation at a young age. OBJECTIVE: The aim of this study was to investigate long-term functional outcome, quality of life, body image, and sexual function after restorative proctocolectomy with IPAA in young patients with familial adenomatous polyposis or ulcerative colitis. DESIGN, SETTINGS, AND PATIENTS: The study consisted of a retrospective review of medical records and questionnaire follow-up of 26 consecutive patients with familial adenomatous polyposis or ulcerative colitis who had undergone surgery between January 1992 and October 2008 at the Maastricht University Medical Center, were aged 10 to 24 years at the time of surgery, and had at least 1 year of follow-up after surgery. MAIN OUTCOME MEASURES: We reviewed medical records from an institutional database regarding surgical procedures and short- and long-term complications. At the end of 2009, validated questionnaires covering bowel function (Colorectal Functional Outcome Questionnaire), quality of life (Short Form-36 and Gastrointestinal Quality of Life Index), body image and cosmesis (Body Image Questionnaire), and sexual function (International Index of Erectile Function for men and Female Sexual Function Index for women) were mailed to patients. RESULTS: Median age at surgery was 18 years, and median follow-up was 12.5 (range, 2-18) years. Long-term colorectal complications occurred in 23 patients (88%), and were directly related to the surgery in 20 patients (77%). Five patients needed pouch excision. The questionnaire response rate was 88%. Bowel function, quality-of-life, and body image and cosmesis scores were all lower in patients than in historical normal control populations. Men did not report impotence or retrograde ejaculation, but 50% of women reported sexual dysfunction. LIMITATIONS: This was a retrospective study in a small number of patients from a single institution with no comparison groups. CONCLUSIONS: Restorative proctocolectomy with IPAA can be performed in young patients with an acceptable functional outcome, but at the cost of relatively high complication rates, poor body image and cosmesis, and a high rate of sexual dysfunction in women. Because young patients undergoing this surgical procedure may experience negative long-term effects, surgeons should be aware of all potential consequences, inform patients as to what to expect, and ensure long-term follow-up to deal with long-term complications.

Guided treatment improves outcome of patients with enterocutaneous fistulas.

BACKGROUND: The present study was designed to evaluate the effects of guided treatment of patients with an enterocutaneous fistula and to evaluate the effect of prolonged period of convalescence on outcome. METHODS: All consecutive patients with an enterocutaneous fistula treated between 2006 and 2010 were included in this study. Patient information was gathered prospectively. Treatment of patients focused on sepsis control, optimization of nutritional status, wound care, establishing the anatomy of the fistula, timing of surgery, and surgical principles. Outcome included spontaneous and surgical closure, mortality, and postoperative recurrence. The relationship between period of convalescence and recurrence rate was determined by combining the present prospective cohort with a historical cohort from our group. RESULTS: Between 2006 and 2010, 79 patients underwent focused treatment for enterocutaneous fistula. Cox regression analysis showed that period of convalescence related significantly with recurrence of the fistula (hazard ratio 0.99; 95 % confidence interval 0.98-0.999; p = 0.04). Spontaneous closure occurred in 23 (29 %) patients after a median period of convalescence of 39 (range 7-163) days. Forty-nine patients underwent operative repair after median period of 101 (range 7-374) days and achieved closure in 47 (96 %). Overall, eight patients (10 %) died. CONCLUSIONS: Prolonging period of convalescence for patients with enterocutaneous fistulas improves spontaneous closure and reduces recurrence rate.

Laparoscopic liver resection in the Netherlands: how far are we?

BACKGROUND: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands. METHODS: A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Furthermore, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery. RESULTS: The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ significantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparoscopic liver resections were performed in 2010. CONCLUSION: The systematic review revealed that very few laparoscopic liver resections were performed in the Netherlands in the previous millennium. The matched case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years.

[A new technique for inguinal hernia repair in children: laparoscopic percutaneous inguinal ring suturing]. / Nieuwe behandeling voor kinderen met een liesbreuk.

Inguinal hernia repair is one of the most frequently performed operations in the pediatric population and laparoscopic hernia repair is currently increasingly performed in Dutch academic and non-academic hospitals. The laparoscopic PIRS-technique is invented by Prof. Dr. D. Patkowski and is an extra-corporeal technique that uses one trocar for the camera and uses an subcutaneous knotted suture. Compared to the open technique, the PIRS-technique offers the possibility for contralateral inspection without making an extra incision and, in case of a contralateral patent processus vaginalis (CPPV), offers the possibility for the simultaneous repair of the CPPV. This prevents the development of a metachronous contralateral inguinal hernia (MCIH), one of the most frequent reason for re-operation after open inguinal hernia repair. This will result in less operations, less exposure to general anesthesia, less hospital admissions and less visits to the general practitioner and emergency department.

Urinary ammonia excretion increases acutely during living donor liver transplantation.

INTRODUCTION: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis. AIM: The present study investigated the consequences of a hepatectomy and subsequent implantation of a partial liver graft on arterial ammonia concentrations and urinary ammonia excretion during a living donor liver transplantation (LDLTx). METHODS: Patients with end-stage liver disease undergoing LDLTx were selected. Samples of arterial blood and urine were taken before, during and 2 h after the anhepatic phase. Differences were tested using Wilcoxon's test. Results are given as median and range. RESULTS: Eleven adult patients undergoing an LDLTx were included. Before hepatectomy, arterial ammonia concentrations were 89 µM (40-156 µM), increasing to 146 µM (102-229 µM) (P<0.001) during the anhepatic phase and returning to 79 µM (46-111 µM) (P<0.01) after reperfusion. Urinary ammonia excretion was initially 1.06 mmol/h (0.02-6.00 mmol/h), increasing to 3.81 mmol/h (0.32-12.55 mmol/h) (P=0.004) during the anhepatic phase and further increasing to 4.00 mmol/h (0.79-9.51 mmol/h) (P=0.013) after reperfusion. CONCLUSION: The kidney significantly increased urinary ammonia excretion during the anhepatic phase, which was sustained after reperfusion, contributing to the rapid decrease of ammonia concentrations. Accordingly, the plasma ammonia concentrations measured directly after LTx cannot simply be used as a read-out of initial liver graft function.

Time-efficiency and hospital costs of open compared with laparoscopic groin hernia repair in a teaching hospital.

BACKGROUND: Time efficiency and hospital costs may influence the preferred method of groin hernia repair. Despite growing expertise in laparoscopic hernia repair, knowledge on the actual costs and the potential financial advantages over open hernia repair are limited. METHODS: A single-center retrospective cohort study comparing hospital costs and time-efficiency of open-mesh (Lichtenstein) and laparoscopic groin hernia repair between 2010 and 2015, including a comparison of surgeons and residents, was conducted. Secondary outcomes were length of hospital stay, complication and recurrence rates. RESULTS: Nine hundred forty-seven open and 449 laparoscopic groin hernia repairs were included. Unilateral open repair showed a shorter operation theatre occupancy (63.5 min±17.2 vs. 71.9 min±19.9, P<0.001) and lower total costs (€ 974.51±266.67 vs. € 1165.32±285.94, P<0.001) compared with laparoscopic repair. Residents had longer operative times compared with surgeons in the unilateral open procedure (43.8±13.4 min vs. 34.5±16.3 min, P<0.001), in the unilateral laparoscopic procedure (46.9±16.6 min vs. 41.7±18.7 min, P<0.001) and higher total costs in the unilateral open procedure (€ 1007.47±238.58 vs. € 909.35±305.00, P<0.001). There were no significant differences in complication and recurrence rates between residents and surgeons. CONCLUSIONS: Open-mesh hernia repair appears to be superior in costs for both uni- and bilateral groin hernias when performed by surgeons as well as residents. Residents had higher total costs and longer operation times in the unilateral open groin hernia group when compared with surgeons, yet overall complications and recurrence rates were similar in all groups suggesting that residents are sometimes more expensive and slower, but just as safe.

Comparison of intra- and extra-corporeal laparoscopic hernia repair in children: A systematic review and pooled data-analysis.

BACKGROUND: Laparoscopic surgery is increasingly used to repair paediatric inguinal hernias and can be divided into intra- or extra-corporeal closing techniques. No statement regarding the superiority of one of the two techniques can be made. This study aims to provide evidence supporting the superiority of intra- or extra-corporeal suturing technique. METHODS: A systematic literature search was conducted using PubMed, Embase, MEDLINE, and Cochrane Library databases. Randomised controlled trials and prospective studies comparing different laparoscopic techniques were eligible for inclusion. Data were pooled using a random-effects model, comparing single-port extra-peritoneal closure to intra-peritoneal purse string suture closing. Primary outcome was recurrence rate. Secondary outcomes were duration of surgery (min), peri­ and post-operative complications (i.e. injury of spermatic vessels or spermatic cord, tuba lesions, bleeding and apnoea, haematoma/scrotal oedema, hydrocele, wound infection, iatrogenic ascent of the testis and testicular atrophy), contralateral patent processus vaginalis (CPPV) rate, post-operative pain, length of hospital stay and cosmetic appearance of the wound. RESULTS: Fifteen studies (n = 3680 patients, age range 0.5-12 years, follow-up range 3-10 months) were included is this systematic review. Intra-corporeal hernia repair was performed in 738 children and extra-corporeal repair was performed in 2942 children. A pooled data analysis could only be performed for the single port extra-corporeal closing technique and the three port intra-corporeal closing technique. We found that recurrence rate was lower in the single-port extra-corporeal closing technique compared to the intra-corporeal purse suture closing technique (0.6% vs 5.5%, 95% CI 0.107 (0.024-0.477); p < 0.001). Operation time was shorter for extra-corporeal unilateral and bilateral inguinal hernia repair compared with intra-corporeal approach, but no pooled data analysis could be performed. Due to the presence of substantial heterogeneity, it was not possible to assess other outcome measures. CONCLUSION: Single-port extra-corporeal closure seems to result in less recurrent hernias and a shorter operative time compared to intra-corporeal purse suture closing technique. No difference regarding peri­ and post-operative complications could be found and no statements regarding the length of hospital admission, post-operative pain and cosmetics could be made due to substantial heterogeneity. LEVEL OF EVIDENCE: Level II.

Long-term quality of life in patients with rectal cancer: association with severe postoperative complications and presence of a stoma.

PURPOSE: The purpose of this study was to evaluate the impact of postoperative complications and the presence of a stoma on long-term quality of life in patients with rectal cancer. METHODS: Consecutive patients with an adenocarcinoma of the rectum who underwent surgery at Maastricht University Medical Center or VieCuri Medical Center between 2003 and 2005 were included in this study. Data on surgical treatment and complications were collected. Severe postoperative complications were classified according to a standardized complication severity score. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer core and colorectal cancer-specific quality-of-life questionnaires. RESULTS: One hundred seventy patients received a questionnaire, and 121 (71%) responded. Of the responders, 33 (27.3%) patients suffered from severe postoperative complications. The median follow-up was 36 months. In the univariate analysis, patients with severe postoperative complications had a lower score on physical functioning (73 vs. 85, P = 0.031) and higher scores on pain (17 vs. 0, P = 0.025) and fatigue (33 vs. 22, P = 0.036). Stoma construction (n = 51) was associated with a higher global health status (83 vs. 75, P = 0.019), and these patients reported fewer gastrointestinal problems (P = 0.001). CONCLUSION: Severe postoperative complications seem to be associated with several lower quality-of-life subscores over the long term. In contrast, a stoma is associated with improved global health status and leads to fewer gastrointestinal complaints. In patients prone to complications, it may be sensible to avoid creating a low anastomosis and to construct a permanent stoma immediately.

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area. Relevance for patients:This review focuses on the role of mitochondrial dysfunction in liver injury mechanisms of clinically important drugs like acetaminophen, diclofenac, rifampicin, isoniazid, amiodarone and others. A better understanding ofthe mechanisms in animal models and their translation to patients will be critical for the identification of new therapeutic targets.

FXR agonism protects against liver injury in a rat model of intestinal failure-associated liver disease.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a clinical challenge. The pathophysiol-ogy is multifactorial and remains poorly understood. Disturbed recirculation of bile salts, e.g. due to loss of bile via an enterocutaneous fistula, is considered a major contributing factor. We hypothesize that impaired signaling via the bile salt receptor FXR underlies the development of IFALD. The aim of this study was to investigate whether activation of FXR improves liver homeostasis during chronic loss of bile in rats. METHODS: To study consequences of chronic loss of bile, rats underwent external biliary drainage (EBD) or sham surgery for seven days, and the prophylactic potential of the FXR agonist INT-747 was assessed. RESULTS: EBD for 7 days resulted in liver test abnormalities and histological liver damage. Expression of the intestinal FXR target gene Fgf15 was undetectable after EBD, and this was accompanied by an anticipated increase in hepatic Cyp7a1 expression, indicating increased bile salt synthesis. Treatment with INT-747 improved serum biochemistry, reduced loss of bile fluid in drained rats and prevented development of drainage-associated histological liver injury. CONCLUSIONS: EBD results in extensive hepatobiliary injury and cholestasis. These data suggest that FXR activation might be a novel therapy in preventing liver dysfunction in patients with intestinal failure. RELEVANCE FOR PATIENTS: This study demonstrates that chronic loss of bile causes liver injury in rats. Abro-gated recycling of bile salts impairing of enterohepatic bile salt/FXR signaling underlies these pathological changes, as administration of FXR agonist INT747 prevents biliary drainage-induced liver damage. Phar-macological activation of FXR might be a therapeutic strategy to treat disorders accompanied by a per-turbed enterohepatic circulation such as intestinal failure-associated liver disease.

Sentinel Node Procedure Obsolete in Lumpectomy for Ductal Carcinoma In Situ.

BACKGROUND: Patients with a preoperative needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) may have an indication for a sentinel lymph node biopsy if invasive carcinoma is found. We investigated how often a positive sentinel node and invasive carcinoma occurred in patients with a preoperative diagnosis of DCIS and whether this influenced the adjuvant regime. MATERIALS AND METHODS: From 2005 to 2014, the records of 240 patients with needle-biopsy diagnosis of DCIS were retrospectively reviewed for postoperative pathology outcomes of the sentinel node and breast, and decisions on adjuvant treatment. Descriptive statistics and univariable and multivariable analysis were used. RESULTS: A total of 160 of 240 patients underwent a sentinel node biopsy. Sixteen of 85 patients undergoing lumpectomy had occult invasive cancer. One patient had a micrometastasis. In patients undergoing mastectomy, 30 of 155 patients had occult invasive cancer. One patient had a micrometastasis, and 3 had a macrometastases. Eleven patients received adjuvant treatment as a result of invasive cancer. Three patients received adjuvant treatment (radiotherapy of the axilla or axillary dissection) because of node positivity. These patients underwent a primary mastectomy. CONCLUSION: A positive sentinel lymph node biopsy in patients with needle-biopsy diagnosis of ductal DCIS is rare and rarely changes adjuvant regimes. Current Dutch guidelines should be updated.

Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease.

BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. METHODS: Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. RESULTS: PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. CONCLUSIONS: This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This animal model serves as an experimental model to further investigate the pathogenesis of PNALD inflicted by steatosis and cholestasis.