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Purpose: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers., Methods: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease., Results: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors., Conclusion: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade., (© 2023. The Author(s).)

Background: Long-term quality of life (QoL) after liver resection is becoming increasingly important, as improvements in operative methods and perioperative care have decreased morbidity and mortality rates. In this study, postoperative QoL after resection of benign or malignant liver tumours was evaluated., Methods: In this single-centre study, QoL was evaluated prospectively using the European Organisation for Research and Treatment of Cancer QLQ-C30 and the liver-specific QLQ-LMC21 module before, and 1, 3, 6 and 12 months after open or laparoscopic liver surgery., Results: Between June 2007 and January 2013, 188 patients (130 with malignant and 58 with benign tumours) requiring major liver resection were included. Global health status was no different between the two groups before and 1 month after liver resection. All patients showed an improvement in global health status at 3, 6 and 12 months after surgery. Patients with benign tumours had better global health status than those with malignant tumours at these time points (P < 0·001, P = 0·002 and P = 0·006 respectively). Patients with benign disease had better physical function scores (P = 0·011, P = 0·025 and P = 0·041) and lower fatigue scores (P = 0·001, P = 0·002 and P = 0·002) at 3, 6 and 12 months than those with malignant disease., Conclusion: This study confirmed overall good QoL in patients undergoing liver resection for benign or malignant tumours, which improved after surgery. Benign diseases were associated with better short- and long-term QoL scores., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Surgical hand disinfection (SHD) is likely to be influenced by various factors. The aim of this study was to evaluate the effect of listening to music on the duration of SHD. In total, 236 SHD procedures were recorded on video. The duration of SHD exceeded 2min in both the intervention group and the control group, with background music unable to achieve an increase in the time spent scrubbing. However, listening to music reduced the proportion of very short scrub times (<90s) from 17% to 9% (P=0.07). The following four factors increased mean scrub time significantly: female sex; lower staff seniority; scrubbing hands in groups; and use of a stopwatch. Although the improvement observed did not reach significance, it is suggested that background music may be useful for the 10% of healthcare workers who perform very short scrubs., (Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Image-guided systems have recently been introduced for their application in liver surgery. We aimed to identify and propose suitable indications for image-guided navigation systems in the domain of open oncologic liver surgery and, more specifically, in the setting of liver resection with and without microwave ablation., Method: Retrospective analysis was conducted in patients undergoing liver resection with and without microwave ablation using an intraoperative image-guided stereotactic system during three stages of technological development (accuracy: 8.4 ± 4.4 mm in phase I and 8.4 ± 6.5 mm in phase II versus 4.5 ± 3.6 mm in phase III). It was evaluated, in which indications image-guided surgery was used according to the different stages of technical development., Results: Between 2009 and 2013, 65 patients underwent image-guided surgical treatment, resection alone (n = 38), ablation alone (n = 11), or a combination thereof (n = 16). With increasing accuracy of the system, image guidance was progressively used for atypical resections and combined microwave ablation and resection instead of formal liver resection (p < 0.0001)., Conclusion: Clinical application of image guidance is feasible, while its efficacy is subject to accuracy. The concept of image guidance has been shown to be increasingly efficient for selected indications in liver surgery. While accuracy of available technology is increasing pertaining to technological advancements, more and more previously untreatable scenarios such as multiple small, bilobar lesions and so-called vanishing lesions come within reach.

For patients with extensive bilobar colorectal liver metastases (CRLM), initial surgery may not be feasible and a multimodal approach including microwave ablation (MWA) provides the only chance for prolonged survival. Intraoperative navigation systems may improve the accuracy of ablation and surgical resection of so-called "vanishing lesions", ultimately improving patient outcome. Clinical application of intraoperative navigated liver surgery is illustrated in a patient undergoing combined resection/MWA for multiple, synchronous, bilobar CRLM. Regular follow-up with computed tomography (CT) allowed for temporal development of the ablation zones. Of the ten lesions detected in a preoperative CT scan, the largest lesion was resected and the others were ablated using an intraoperative navigation system. Twelve months post-surgery a new lesion (Seg IVa) was detected and treated by trans-arterial embolization. Nineteen months post-surgery new liver and lung metastases were detected and a palliative chemotherapy started. The patient passed away four years after initial diagnosis. For patients with extensive CRLM not treatable by standard surgery, navigated MWA/resection may provide excellent tumor control, improving longer-term survival. Intraoperative navigation systems provide precise, real-time information to the surgeon, aiding the decision-making process and substantially improving the accuracy of both ablation and resection. Regular follow-ups including 3D modeling allow for early discrimination between ablation zones and recurrent tumor lesions.

Unlabelled: Chronic hepatitis occurs when effector lymphocytes are recruited to the liver from blood and retained in tissue to interact with target cells, such as hepatocytes or bile ducts (BDs). Vascular cell adhesion molecule 1 (VCAM-1; CD106), a member of the immunoglobulin superfamily, supports leukocyte adhesion by binding α4β1 integrins and is critical for the recruitment of monocytes and lymphocytes during inflammation. We detected VCAM-1 on cholangiocytes in chronic liver disease (CLD) and hypothesized that biliary expression of VCAM-1 contributes to the persistence of liver inflammation. Hence, in this study, we examined whether cholangiocyte expression of VCAM-1 promotes the survival of intrahepatic α4β1 expressing effector T cells. We examined interactions between primary human cholangiocytes and isolated intrahepatic T cells ex vivo and in vivo using the Ova-bil antigen-driven murine model of biliary inflammation. VCAM-1 was detected on BDs in CLDs (primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease, and chronic hepatitis C), and human cholangiocytes expressed VCAM-1 in response to tumor necrosis factor alpha alone or in combination with CD40L or interleukin-17. Liver-derived T cells adhered to cholangiocytes in vitro by α4β1, which resulted in signaling through nuclear factor kappa B p65, protein kinase B1, and p38 mitogen-activated protein kinase phosphorylation. This led to increased mitochondrial B-cell lymphoma 2 accumulation and decreased activation of caspase 3, causing increased cell survival. We confirmed our findings in a murine model of hepatobiliary inflammation where inhibition of VCAM-1 decreased liver inflammation by reducing lymphocyte recruitment and increasing CD8 and T helper 17 CD4 T-cell survival., Conclusions: VCAM-1 expression by cholangiocytes contributes to persistent inflammation by conferring a survival signal to α4β1 expressing proinflammatory T lymphocytes in CLD., (© 2014 by the American Association for the Study of Liver Diseases.)

Background: While previous studies suggest advantages of minimally invasive surgery in living donor nephrectomy, similar data are lacking for kidney transplant recipients. Our aim was to prospectively evaluate short- and long-term outcome for kidney transplant recipients, comparing a short transverse (ST) to a classical hockey-stick (HS) incision., Methods: Sixty-six patients were randomized into two groups: ST vs. HS from January 2008 to May 2010. ST was defined as incision length ≤9 cm and HS as >14 cm. Perioperative data were collected, with evaluation of intra- and postoperative complications and quality of recovery (QoR) score., Results: There were no significant differences in patient demographics, early or long-term postoperative pain. There were no significant differences in QoR scores between the ST and HS group. Predictive for a worse QoR was persisting incisional pain at the 30-month follow-up. Thirty-days mortality, morbidity, and long-term kidney function did not differ between the two groups (p = 1.00, p = 0.62 and p = 0.66, respectively)., Conclusions: Patient satisfaction as well as graft function and patient mortality was not influenced by incision length. With patient and graft safety being paramount, especially in times of organ shortage, incision length should reflect the requirement for a successful transplantation and not be a measure of feasibility., (© 2013 John Wiley & Sons A/S.)

Background: Whether total extraperitoneal inguinal hernia repair (TEP) is associated with worse outcomes than transabdominal preperitoneal inguinal hernia repair (TAPP) continues to be a matter of debate. The objective of this large cohort study is to compare outcomes between patients undergoing TEP or TAPP., Methods: Based on prospective data of the Swiss association of laparoscopic and thoracoscopic surgery, all patients undergoing unilateral TEP or TAPP between 1995 and 2006 were included. The following outcomes were compared: conversion rates, intraoperative and postoperative complications, duration of operation., Results: Data on 4,552 patients undergoing TEP (n=3,457) and TAPP (n=1,095) were collected prospectively. Average age and American Society of Anesthesiologists score were similar in the two groups. Patients undergoing TEP had a significantly higher rate of intraoperative complications (TEP 1.9% vs. TAPP 0.9%, p=0.029) and surgical postoperative complications (TEP: 2.3% vs. TAPP: 0.8%, p=0.003). The postoperative length of stay was longer for patients undergoing TAPP (2.9 vs. 2.3 days, p=0.002), whereas the duration of the operation was longer for TEP (66.6 vs. 59.0 min, p<0.001) and the conversion rate was higher (TEP 1.0% vs. TAPP 0.2%, p=0.011)., Conclusions: This study is one of the first population-based analyses comparing TEP and TAPP in a prospective cohort of more than 4,500 patients. Intraoperative and surgical postoperative complications were significantly higher in patients undergoing TEP. TEP is also associated with longer operating times and higher conversion rates. Therefore, on a population-based level, the TAPP technique appears to be superior to the TEP repair in patients undergoing unilateral inguinal hernia repair.

Objective: Courses in the Advanced Trauma Life Support are a well-accepted concept throughout the world for training in the emergency treatment of polytraumatized patients. Switzerland, a multilingual country with a long tradition of multidisciplinary collaboration in trauma care, introduced its first student courses in 1998. Unlike some countries where the courses are attended only by surgeons, instructors and students in Switzerland include surgeons, anaesthetists and physicians from other specialties., Methods: Course evaluation assessments and instructor and student demographic data were analysed retrospectively using univariate analyses (Pearson correlation), multivariate analysis of variance, with post-hoc analysis and Bonferroni correction, and stepwise linear regression analysis., Results: Between 1998 and 2003, 922 students attended 58 courses available for evaluation, with 22 338 ratings of different modules. Students rated practical (r=0.076) instruction significantly better than lectures (r=-0.072), gave better rating for women instructors (r=0.026) and for instructors teaching outside their specialty (r=-0.027). Women and participants in French-speaking courses gave better ratings. Ratings by anaesthetists were more critical than by surgeons and students from other specialties., Conclusion: The practical format of Advanced Trauma Life Support courses is appreciated by students, and the involvement of anaesthetists, general practitioners and other specialists as instructors is successful. Course rating was influenced by chosen specialty, sex and language of the students, and this should be taken into consideration when evaluating course modules and instructors.

Background/aim: Acute non-specific abdominal pain (NSAP) is prevalent in 6-25% of the general population and is a common cause of admission to the emergency department (ED). Despite involvement of substantial financial and human resources, there are few data on long-term outcome after initial diagnosis. The aim of this study was to evaluate long-term outcome of patients initially admitted with NSAP to an ED., Methods: The study involves a 5-year follow-up analysis of prospectively collected data on 104 patients admitted to our ED in 2003 with NSAP. Primary end-point was clinical outcome 5 years after initial ED admission. Predictive risk factors were assessed using a multivariate regression model., Results: 29 patients (28%) had recurring NSAP 5 years after initial ED admission, 76% of these patients received (multiple) diagnostic examinations and 13% eventually required diagnostic (or therapeutic) surgery. Although approximately half of patients with recurring NSAP eventually received a definite diagnosis, 30% still suffered from recurrent abdominal pain. Using regression analysis, no single factor in our dataset could be identified as a predictor for NSAP persistence., Conclusion: The long-term impact for patients initially admitted to our ED with acute NSAP is significant--28% of patients continue to suffer from recurring NSAP after 5 years. NSAP therefore remains, despite more advanced diagnostic tools, a true and, as yet, unsolved problem., (© 2010 The Authors. Internal Medicine Journal © 2010 Royal Australasian College of Physicians.)

Background: Numerous studies have shown differences in pain perception between men and women, which may affect pain management strategies., Aim: Our primary aim was to investigate whether there are gender-based differences in pain management in patients admitted to our emergency department with acute, non-specific abdominal pain (NSAP). Our secondary aim was to evaluate if other factors influence administration of analgesia for patients admitted with NSAP., Methods: From June 2007 to June 2008, we carried out a retrospective, gender-based, frequency-matched control study with 150 patients (75 consecutive men and 75 women) who presented with NSAP at our emergency department. Pain was documented using a numerical rating scale ('0' no pain, '10' most severe pain). A multinomial regression model was used to assess factors that might influence pain management., Results: No statistically significant difference was seen between men and women with respect to pain management (P= 0.085). Younger patients were, however, more likely to receive weaker (P= 0.011) and fewer analgesics (P < 0.001). Patients with previous abdominal surgery (P= 0.012), known chronic pain conditions (P= 0.029) or relevant comorbidities (P= 0.048) received stronger analgesia. Nationality (P= 0.244), employment status (P= 0.988), time of admission (P= 0.487) and known psychiatric illness (P= 0.579) did not influence pain management., Conclusions: No statistically significant gender-dependent differences in pain management were observed. However, younger patients received less potent analgesic treatment. There is no reason for certain groups to receive suboptimal treatment, and greater efforts should be made to offer consistent treatment to all patients., (© 2010 The Authors. Journal compilation © 2010 Royal Australasian College of Physicians.)

Background: Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA., Methods: A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival., Results: Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival., Conclusion: In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The Estimation of Physiologic Ability and Surgical Stress score was designed to predict postoperative morbidity and mortality in general surgery. Our study aims to evaluate its use and accuracy in estimating postoperative outcome after elective pancreatic surgery., Methods: Between 2002 and 2007, approximately 304 patients requiring pancreatic resection at our institution were recorded prospectively and evaluated retrospectively. The patients' preoperative risk score, surgical stress score (SSS), and comprehensive risk score (CRS) were calculated and compared with the severity of postoperative morbidity, where mortality was regarded as the most severe postoperative complication., Results: Observed and predicted mortality rates were 2.9% and 2.0%, respectively. Mean CRS was higher in patients who died than in patients that survived, but this difference was not statistically significant (P = 0.20). Preoperative risk score, SSS, and CRS did not differ between patients with and without complications (preoperative risk score: P = 0.32; SSS: P = 0.22; CRS: P = 0.13). Estimation of Physiologic Ability and Surgical Stress particularly underpredicted morbidity in patients with a CRS between 0.0 and less than 0.5., Conclusions: The Estimation of Physiologic Ability and Surgical Stress scoring system is an ineffective predictor of complications after pancreatic resection. Further refinements to the score calculation are warranted to provide accurate prediction of immediate surgical outcome after pancreatic surgery.

Surgical and anesthesia-related techniques may reduce physical stress for patients undergoing high-risk surgery, but major surgery is increasingly performed in patients with substantial comorbidities. Strategies for improving the outcome for such patients include approaches that both increase tissue oxygen delivery and reduce metabolic demand. However, these strategies have produced conflicting results. To understand the success and failure of attempts to improve postoperative outcome, the pathophysiology of perioperative hemodynamic, metabolic, and immunological alterations should be analyzed. Our aim in this review is to provide a survey of fields of opportunities for improving outcome after major surgery. The issues are approached from 3 different angles: the view of the patient, the view of the surgical intervention, and the view of the anesthesia. Special attention is also given to what could be considered the result of the interaction among the 3: perioperative inflammation and immune response., (© 2011 International Anesthesia Research Society)

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon.A search of the literature has made it apparent that there is no straightforward answer to the question what to do with patients with free intraabdominal fluid on CT scanning but without signs of solid organ injury. In hemodynamically unstable patients, free intraabdominal fluid in the absence of solid organ injury usually mandates immediate surgical intervention. For patients with blunt abdominal trauma and more than just a trace of free intraabdominal fluid or for patients with signs of peritonitis, the threshold for a surgical exploration - preferably by a laparoscopic approach - should be low. Based on the available information, we aim to provide the reader with an overview of the current literature with specific emphasis on diagnostic and therapeutic approaches to this problem and suggest a possible algorithm, which might help with the adequate treatment of such patients.

N-myc downstream-regulated gene 1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein destabilization. On the contrary, inhibition of Hsp90 led to a transcriptional increase of NDRG1 protein which was associated with cell growth arrest. We also observed that GA inhibited the phosphorylation of NDRG1 by targeting its regulating kinases, serum- and glucocorticoid-induced kinase 1 (SGK1) and glycogen synthase kinase 3 beta (GSK3beta). We demonstrate that in the presence of GA, GSK3beta protein and activity were decreased thus indicating that Hsp90 is necessary for GSK3beta stability. Taken together, our data demonstrate that NDRG1 is not a classic client protein but interacts with Hsp90 and is still dually regulated by Hsp90 at a transcriptional and post-translational level. Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90.

Background: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease., Methods: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module., Results: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5 months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p = 0.367). Neither the extent of the resection (> or =2 segments vs. <2 segments; p = 0.975; OR = 0.988; 95% CI = 0.461-2.119) nor patient age had a significant influence on overall QoL (p = 0.092)., Conclusions: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor QoL.

Background: The estimation of physiologic ability and surgical stress (E-PASS) has been used to produce a numerical estimate of expected mortality and morbidity after elective gastrointestinal surgery. The aim of this study was to validate E-PASS in a selected cohort of patients requiring liver resections (LR)., Methods: In this retrospective study, E-PASS predictor equations for morbidity and mortality were applied to the prospective data from 243 patients requiring LR. The observed rates were compared with predicted rates using Fisher's exact test. The discriminative capability of E-PASS was evaluated using receiver-operating characteristic (ROC) curve analysis., Results: The observed and predicted overall mortality rates were both 3.3% and the morbidity rates were 31.3 and 26.9%, respectively. There was a significant difference in the comprehensive risk scores for deceased and surviving patients (p = 0.043). However, the scores for patients with or without complications were not significantly different (p = 0.120). Subsequent ROC curve analysis revealed a poor predictive accuracy for morbidity., Conclusions: The E-PASS score seems to effectively predict mortality in this specific group of patients but is a poor predictor of complications. A new modified logistic regression might be required for LR in order to better predict the postoperative outcome.

The purpose of this chapter is to give a practical and clinically-orientated overview over the best radiological imaging for the most frequent diseases of the hepato-pancreatico-biliary system. For this purpose the liver parenchyma, the biliary tree, the pancreas and the hepatic vasculature are dealt with separately. According to the presumed pathology, the most cost-saving and time-efficient radiological imaging can then be chosen.

Introduction: The incidence of duodenal diverticula (DD) found at autopsy may be as high as 22%. Perforation is the least frequent but also the most serious complication. This case series gives an overview of the management of this rare entity., Methods: This study is a case series of eight patients treated for symptomatic DD., Results: Two patients had a perforated DD. One perforation was in segments III-IV, which to our knowledge is the first published case; the other perforation was in segment II. A segmental duodenectomy was performed in the first patient and a pylorus-preserving duodeno-pancreatectomy (pp-Whipple) in the second. A third patient with chronic complaints and recurring episodes of fever required an excision of the DD. In a fourth patient with biliary and pancreatic obstruction, a pp-Whipple was carried out, and a DD was discovered as the underlying cause. Four patients (one small perforation, one hemorrhage, and two recurrent cholangitis/pancreatitis caused by a DD) were treated conservatively., Conclusions: Symptomatic DD and, in particular, perforations are rare, encompass diagnostic challenges, and may require technically demanding surgical or endoscopic interventions. The diagnostic value of forward-looking gastroduodenoscopy in this setting seems limited. If duodenoscopy is performed at all, the use of a side-viewing endoscope is mandatory.