A 'traumatic' mechanical small bowel obstruction after blunt pelvic trauma.

Traumatic abdominal wall hernia (TAWH) is a rare form of herniation caused by blunt trauma that can lead to intestinal obstruction. This report details a rare case of delayed mechanical ileus resulting from TAWH due to an acetabular fracture. The patient was successfully treated with laparoscopic closure of the peritoneal orifice, followed by orthopaedic repair of the fracture. The presented scenario underlines the importance of timely diagnosis and interdisciplinary collaboration in addressing complex TAWH cases.

A rare case of a sporadic retroperitoneal hemangioblastoma.

Hemangioblastoma is a rare, benign, and morphologically distinctive tumor. In most cases, the tumor involves the central nervous system. Extraneural occurrences are rare, with just a few reports of hemangioblastoma situated outside of neural tissue, such as the retroperitoneum. We report a case of sporadic retroperitoneal hemangioblastoma in an 87-year-old male patient, diagnosed as an incidental finding in a CT scan performed because of kidney stone disease. The CT scan showed a mass in the retroperitoneum posterior to the inferior vena cava. The patient reported no remarkable symptoms. We describe our path to diagnosis, the possible differential diagnosis for retroperitoneal masses, and the histopathologic features of the tumor. There are <250 reported extra neuraxial hemangioblastomas and just 14 reported cases situated outside of the neural tissue. Our case is the eighth case report of a hemangioblastoma arising from the soft tissue of the retroperitoneum.

Evaluation of the Introduction of a Colorectal Bundle in Left Sided Colorectal Resections (EvaCol): Study Protocol of a Multicentre, Observational Trial.

Purpose: Overall complication and leak rates in colorectal surgery showed only minor improvements over the last years and remain still high. While the introduction of the WHO Safer Surgery Checklist has shown a reduction of overall operative mortality and morbidity in general surgery, only minor attempts have been made to improve outcomes by standardizing perioperative processes in colorectal surgery. Nevertheless, a number of singular interventions have been found reducing postoperative complications in colorectal surgery. The aim of the present study is to combine nine of these measures to a catalogue called colorectal bundle (CB). This will help to standardize pre-, intra-, and post-operative processes and therefore eventually reduce complication rates after colorectal surgery. Methods: The study will be performed among nine contributing hospitals in the extended north-western part of Switzerland. In the 6-month lasting control period the patients will be treated according to the local standard of each contributing hospital. After a short implementation phase all patients will be treated according to the CB for another 6 months. Afterwards complication rates before and after the implementation of the CB will be compared. Discussion: The overall complication rate in colorectal surgery is still high. The fact that only little progress has been made in recent years underlines the relevance of the current project. It has been shown for other areas of surgery that standardization is an effective measure of reducing postoperative complication rates. We hypothesize that the combination of effective, individual components into the CB can reduce the complication rate. Trial registration: Registered in ClinicalTrials.gov on 11/03/2020; NCT04550156. Highlights: Purpose: Overall complications in colorectal surgery remain still highStandardizing can reduce overall operative mortality and morbidityOnly minor attempts have been made to standardize perioperative processes in colorectal surgerySingular interventions have been found reducing postoperative complicationsThe aim is to combine nine of these measures to a colorectal bundle (CB)The CB will help to reduce complication rates after colorectal surgery Methods: The observational study will be performed among nine hospitals in SwitzerlandSix month the patients will be treated according to the local standardsAfterwards patients will be treated according to the CB for another six monthsComplication rates before and after the implementation of the CB will be compared Discussion: Only little progress has been made to reduce complication rate in colorectal surgeryStandardization is an effective measure of reducing complication ratesThe combination of effective, individual components into the CB can reduce the complication rate.

Report of two rare manifestations of abdominal tuberculosis mimicking neoplasia.

Abdominal tuberculosis (TB) can affect any organ of the gastrointestinal tract, and as a result of its unspecific symptoms, it may even mimic neoplasia. Rare manifestations are difficult to detect even for the trained eye and require clinical suspicion. We report rare cases of a mechanical ileus due to peritoneal TB in a 41-year-old man and an isolated peripancreatic infection in a 54-year-old woman. While in one patient, suspected malignancy led to diagnostic laparoscopy, it led to a total pancreatectomy with splenectomy in the other case. However, both times histology ruled out malignancy and showed unexpected similarities with TB. The patients responded well to medical treatment, although one patient is struggling with pancreatogenic diabetes.

[Current surgical treatment options for liver metastasis]. / Lebermetastasen: aktueller Stand der chirurgischen Behandlungsmöglichkeiten.

Current surgical treatment options for liver metastasis Abstract. Metastasis are the most frequent hepatic tumors. Although current treatment regimens focus highly on interdisciplinarity and are individualized, surgical resection remains the only curative treatment and represents the current gold standard approach. Advances in surgical, systemic and interventional treatment within the last years have resulted in a multidisciplinary therapy, individualized for each patient depending on their disease stage and condition. With these advancements, initially non-resectable liver metastasis can now be candidates for a surgical approach. Neoadjuvant chemotherapy, minimal invasive ablation, two- or multi-staged resections of the liver with or without portal vein embolization have contributed to this development. Advances in surgical and perioperative treatment also account for significantly increased overall survival.

Diagnostic role of the 'white test' with lipidic solution in the early intraoperative identification of open bile ducts for the prevention of bile leakage after liver resection: study protocol for a randomised controlled multicentric superiority trial (BiLe-Trial).

INTRODUCTION: Bile leakage is a frequent complication after liver resection associated with the need of interventional drainage, endoscopic retrograde cholangio pancreatography (ERCP) or reoperation. The intraoperative application of the white test could be a promising strategy to reduce the occurrence of bile leakages. Therefore, we propose to conduct the first multicentric randomised controlled trial with rate of postoperative bile leakage as primary endpoint with and without the white test. METHODS AND ANALYSIS: The Bile-Leakage Trial trial is an investigator-initiated randomised controlled, parallel group, double-blinded, multicentric, superiority trial in four Swiss centres. A total of 210 patients undergoing a resection of at least 2 liver segments will be randomly allocated intraoperatively to either the intervention (identification of open bile ducts with administration of 20-40 mL SMOFlipid5% in the bile tract) or the control group (identification with a white gauze on the liver resection surface).Primary outcome will be the comparison of the postoperative bile leakage rate in both groups within 30 days after liver resection, defined according to the classification of the International Study Group of Liver Surgery. Secondary outcomes will be operative and postoperative complication, including severity grade of the bile leakage, rate of ERCP, interventional drainage, morbidity, intensive care unit stay, and mortality. ETHICS AND DISSEMINATION: The cantonal ethics committees of all participating centres and Swissmedic approved the study. SMOFlipid20% consists of a mixture of oils, no side effects resulting from the intraoperative application of 20-40 mL in the biliary tract with consecutive enteral absorption are expected nor are side effects described in the literature. SMOFlipid20% will be diluted intraoperatively with isotonic saline solution to a concentration of 5%. The results of the BiLe-Trial will be submitted to a peer-reviewed journal regardless of the outcome. As this is an investigator-initiated trial, data are property of the sponsor investigator and can be obtained on request. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID: NCT04523701. Registered on 25 August 2020.Swiss National Clinical Trials Portal (SNCTP), ID: SNCTP000004200. Registered on 20 January 2021. PROTOCOL VERSION: V3.2_14-12-2020_clean.pdf.

Bilateral delayed traumatic diaphragmatic injury.

A 47-year-old patient presented at our emergency department with acute epigastric pain. A thoracic X-ray showed a partially intrathoracic stomach as well as bowel left sided. A following computed tomography scan diagnosed a diaphragmatic hernia. In the patient's history, 20 years ago a serious car accident was reported as the presumable traumatic origin. Intraoperatively, the diaphragmatic hernia was repaired with a direct suture and mesh augmentation. The rest of the abdomen was clear. In a thoracic X-ray following chest tube removal, herniated small bowel appeared intrathoracally on the right. Relaparotomy showed an extensive diaphragmatic hernia with parts of the liver, small bowel and colon in the right thoracic cavity. Only a partial direct repair was possible, an inlay mesh repair was performed. The further recovery was uneventful. Bilateral delayed traumatic diaphragmatic hernias are extremely rare, but with a suggestive trauma history thorough intraoperative exploration of the contralateral side should be evaluated.

wIRA: hyperthermia as a treatment option for intracellular bacteria, with special focus on Chlamydiae and Mycobacteria.

The emergence of antibiotic-resistant bacteria in the last century is alarming and calls for alternative, nonchemical treatment strategies. Thermal medicine uses heat for the treatment of infectious diseases but its use in facultative and obligate intracellular bacteria remains poorly studied. In this review, we summarize previous research on reducing the infectious burden of Mycobacterium ulcerans and Chlamydia trachomatis by using water-filtered infrared A-radiation (wIRA), a special form of heat radiation with high tissue penetration and low thermal load on the skin surface. Mycobacterium ulcerans is a thermosensitive bacterium causing chronic necrotizing skin disease. Therefore, previous data on wIRA-induced improvement of wound healing and reduction of wound infections is summarized first. Then, pathogenesis and treatment of infections with M. ulcerans causing Buruli ulcer and of those with C. trachomatis infecting the ocular conjunctiva and resulting in blinding trachoma are discussed. Both bacteria cause neglected tropical diseases and have similar geographical distributions. Results of previous in vitro and in vivo studies using wIRA on M. ulcerans and C. trachomatis infections are presented. Finally, technical aspects of using wIRA in patients are critically reviewed and open questions driving future research are highlighted. In conclusion, wIRA is a promising tool for reducing infectious burden due to intracellular bacteria such as M. ulcerans and C. trachomatis.

Total Versus Near-total Thyroidectomy in Graves Disease: Results of the Randomized Controlled Multicenter TONIG-trial.

BACKGROUND: Previous data suggest that the incidence of hypoparathyroidism after surgery for Graves disease (GD) is lower after subtotal thyroidectomy compared to total thyroidectomy (TT). The present study evaluated the incidence of postoperative hypoparathyroidism after near-total (NTT) versus TT in GD. METHODS/DESIGN: In a multicenter prospective randomized controlled clinical trial, patients with GD were randomized intraoperatively to NTT or TT. Primary endpoint was the incidence of transient postoperative hypoparathyroidism. Secondary endpoints were permanent hypoparathyroidism, transient recurrent laryngeal nerve palsy (RLNP), reoperations for bleeding, inadvertently removed parathyroid glands, and recurrent hyperthyroidism after 12 months. RESULTS: Eighteen centers randomized 205 patients to either TT (n = 102) or NTT (n = 103) within 16 months. According to intention-to-treat postoperative transient hypoparathyroidism occurred in 19% (20/103) patients after NTT and in 21% (21 of 102) patients after TT (P = 0.84), which persisted >6 months in 2% and 5% of the NTT and TT groups (P = 0.34). The rates of parathyroid autotransplantation (NTT 24% vs TT 28%, P = 0.50) and transient RLNP (NTT 3% vs TT 4%, P = 0.35) was similar in both groups. The rate of reoperations for bleeding tended to be higher in the NTT group (3% vs 0%, P = 0.07) and the rate of inadvertently removed parathyroid glands was significantly higher after NTT (13% vs 3%, P = 0.01). An existing endocrine orbitopathy improved in 35% and 24% after NTT and TT (P = 0.61). Recurrent disease occurred in only 1 patient after TT (P = 0.34). CONCLUSION: NTT for GD is not superior to TT regarding transient postoperative hypoparathyroidism.

Heat for wounds - water-filtered infrared-A (wIRA) for wound healing - a review.

BACKGROUND: Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. wIRA corresponds to the major part of the sun's heat radiation, which reaches the surface of the Earth in moderate climatic zones filtered by water and water vapour of the atmosphere. wIRA promotes healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic cellular effects. METHODS: This publication includes a literature review with search in PubMed/Medline for "water-filtered infrared-A" and "wound"/"ulcus" or "wassergefiltertes Infrarot A" and "Wunde"/"Ulkus", respectively (publications in English and German), and additional analysis of study data. Seven prospective clinical studies (of these six randomized controlled trials (RCT), the largest study with n=400 patients) were identified and included. All randomized controlled clinical trials compare a combination of high standard care plus wIRA treatment vs. high standard care alone. The results below marked with "vs." present these comparisons. RESULTS: wIRA increases tissue temperature (+2.7°C at a tissue depth of 2 cm), tissue oxygen partial pressure (+32% at a tissue depth of 2 cm) and tissue perfusion (effect sizes within the wIRA group). wIRA promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain (with respect to alleviation of pain, without any exception during 230 irradiations, 13.4 vs. 0.0 on a visual analogue scale (VAS 0-100), median difference between groups 13.8, 95% confidence interval (CI) 12.3/16.7, p<0.000001) with a substantially reduced need for analgesics (52-69% less in the three groups with wIRA compared to the three control groups in visceral surgery, p=0.000020 and 0.00037 and 0.0045, respectively; total of 6 vs. 14.5 analgesic tablets on 6 surveyed days (of weeks 1-6) in chronic venous stasis ulcers, median difference -8, 95% CI -10/-5, p=0.000002). Further effects are: Faster reduction of wound area (in severely burned children: 90% reduction of wound size after 9 vs. 13 days, after 9 days 89.2% vs. 49.5% reduction in wound area, median difference 39.5% wound area reduction, 95% CI 36.7%/42.2%, p=0.000011; complete wound closure of chronic venous stasis ulcers after 14 vs. 42 days, median difference -21 days, 95% CI -28/-10, p=0.000005). Better overall evaluation of wound healing (surgical wounds: 88.6 vs. 78.5 on a VAS 0-100, median difference 8.9, 95% CI 6.1/12.0, p<0.000001). Better overall evaluation of the effect of irradiation (79.0 vs. 46.8 on a VAS 0-100 with 50 as neutral point, median difference 27.9, 95% CI 19.8/34.6, p<0.000001). Higher tissue oxygen partial pressure during irradiation with wIRA (at a tissue depth of 2 cm 41.6 vs. 30.2 mmHg, median difference 11.9 mmHg, 95% CI 9.6/14.2 mmHg, p<0.000001). Higher tissue temperature during irradiation with wIRA (at a tissue depth of 2 cm 38.9 vs. 36.4°C, median difference 2.6°C, 95% CI 2.2/2.9°C, p<0.000001). Better cosmetic result (84.5 vs. 76.5 on a VAS 0-100, median difference 7.9, 95% CI 3.7/12.0, p=0.00027). Lower wound infection rate (single preoperative irradiation: 5.1% vs. 12.1% wound infections in total, difference -7.0%, 95% CI -12.8%/-1.3%, p=0.017, of these: late wound infections (postoperative days 9-30) 1.7% vs. 7.7%, difference -6.0%, 95% CI -10.3%/-1.7%, p=0.007). Shorter hospital stay (9 vs. 11 postoperative days, median difference -2 days, 95% CI -3/0 days, p=0.022). Most of the effects have been proven with an evidence level of 1a or 1b. CONCLUSION: Water-filtered infrared-A is a useful complement for the treatment of acute and chronic wounds.

Umbilical Microflora, Antiseptic Skin Preparation, and Surgical Site Infection in Abdominal Surgery.

BACKGROUND: Surgical site infections (SSI) following abdominal surgery are frequent and a major cause of postoperative morbidity and prolonged hospital stay. Besides antibiotic prophylaxis, antiseptic skin preparation is an important measure to prevent SSI. METHODS: Here we prospectively analyzed the effectiveness of antiseptic skin preparation in a cohort of 93 patients undergoing laparotomy, with special emphasis on the umbilical region. RESULTS: The microflora of the umbilicus contained a large number of resident (mostly staphylococci species and corynebacteria) and transient germs (including enterococci species). Following antiseptic skin preparation, bacteria could still be cultured from 24.7% of the patients' umbilici. In case of postoperative SSI, only one of seven SSI was caused by the microorganism that was present in the umbilicus before and after skin preparation. CONCLUSION: Antiseptic skin preparation fails to completely eradicate the microflora of the umbilical region in one quarter of the patients. However, at least in abdominal surgery, the vast majority of SSI are caused by intra-abdominal contamination rather than the skin microflora.

Pain sensation in pancreatic diseases is not uniform: the different facets of pancreatic pain.

AIM: To systematically characterize specific pain patterns in the most frequent pancreatic diseases. METHODS: Pain in patients with chronic pancreatitis (n = 314), pancreatic cancer (n = 469), and other pancreatic tumors (n = 249) including mucinous (n = 20) and serous cystadenoma (n = 31), invasive (n = 37) and non-invasive intraductal papillary mucinous neoplasia (IPMN; n = 48), low stage (n = 18) and high stage neuroendocrine neoplasia (n = 44), and ampullary cancer (n = 51) was registered and correlated with clinicopathological data. Survival times were estimated by the Kaplan-Meier method. Patients alive at the follow-up time were censored. Survival curves were compared statistically using the log-rank test. RESULTS: Forty-nine point one percent of pancreatic cancer patients revealed no pain, whereas in chronic pancreatitis only 18.3% were pain free. In contrary, moderate/severe pain was registered in 15.1% in pancreatic cancer patients that was increased in chronic pancreatitis with up to 34.2%. Serous cystadenoma was asymptomatic in most cases (58.1%), whereas 78.9% of all mucinous cystadenoma patients suffered pain. In neuroendocrine neoplasia pain was not a key clinical symptom since 64% of low stage neuroendocrine neoplasia and 59% of high stage neuroendocrine neoplasia patients were pain free. Cancer localization in the pancreatic body and patients with malignant pancreatic neoplasms were associated with more severe pain. Tumor grading and stage did not show any impact on pain. Only in pancreatic cancer, pain was directly associated with impaired survival. CONCLUSION: Pancreatic pain depicts different patterns of abdominal pain sensation according to the respective pancreatic disorder and does not allow a unification of the term pancreatic pain.

Impact of preoperative local water-filtered infrared A irradiation on postoperative wound healing: a randomized patient- and observer-blinded controlled clinical trial.

OBJECTIVE: In addition to a preoperative antibiotic single-shot prophylaxis, we tested the impact of a one-time preoperative water-filtered infrared A irradiation (wIRA) on postoperative wound healing of patients. BACKGROUND: wIRA improves wound healing in postoperative settings. METHODS: A total of 400 consecutive patients undergoing gastrointestinal surgery were randomly assigned to the treatment group (A) or placebo group (B). We applied wIRA for 20 minutes while patients were prepared for surgery. Patients and observer were blinded to group assignment. Primary endpoints were surgical site infections (SSIs), wound healing, and rate and level of pain within 30 days after surgery. Primary efficacy analysis was carried out on the basis of an intention-to-treat (ITT) population and a full-analysis set (FAS). Missing values of primary outcome variables were considered as SSIs and maximum pain levels in the ITT analysis, respectively. RESULTS FAS: The incidence of SSI was 9 of 178 patients (5.1%) within group A compared with 22 of 182 (12.1%) within group B [P = 0.018; relative risk (RR) = 0.42; 95% CI: 0.18-0.93]. ITT: 32 of 200 (16%) SSIs occurred within group A and 39 of 200 (20%) within group B (P = 0.248) with an RR of 0.74 (95% CI: 0.43-1.28). The wIRA group showed lower postoperative pain at both the ITT (P = 0.092) and the FAS analysis (P = 0.045). CONCLUSIONS: This trial indicates a clinically relevant benefit of one-time application of preoperative wIRA as a supportive addition to prophylactic antibiotics. wIRA contributes to both reduced SSI rates and postoperative pain but also effectively decreases morbidity and related expenses in the health care system.

The impact of MFG-E8 in chronic pancreatitis: potential for future immunotherapy?

BACKGROUND: The glycoprotein MFG-E8 mediates phagocytic clearance of apoptotic cells and influences the pathogenesis and progression of inflammatory diseases. MFG-E8 was shown to attenuate the progression of inflammation and to improve survival in septic rats. Accumulating evidence suggests an immunomodulatory link between MFG-E8 and the pro-inflammatory chemokine fractalkine, which may determine the severity of pain, fibrosis, and inflammation in chronic pancreatitis (CP). METHODS: The expression and localization of MFG-E8 was investigated in CP (n=62), and normal pancreas (NP; n=34) by QRT-PCR, Western-blot and immunohistochemistry analyses. Results were correlated with mRNA expression of fractalkine, CX3CR1, and with the presence and degree of pain and fibrosis. Human pancreatic stellate cells (hPSCs) were isolated from CP tissues and evaluated for MFG-E8 mRNA expression after fractalkine stimulation. RESULTS: MFG-E8-mRNA was significantly overexpressed in CP and isolated hPSCs when compared to NP. Western-blot and immunohistochemistry analysis confirmed accumulation of MFG-E8 in CP, with noticeably increased MFG-E8 immunoreactivity in tubular complexes. MFG-E8 expression correlated significantly with fractalkine expression, severe fibrosis, and the presence of pain in CP patients. Stimulation of hPSCs with fractalkine led to a significant increase in MFG-E8 expression. CONCLUSIONS: In the present study, we demonstrated for the first time that MFG-E8 is significantly up-regulated in CP patients and together with fractalkine correlated noticeably with severe fibrosis and the presence of pain. hPSCs overexpress MFG-E8 upon fractalkine stimulation in vitro, which underlines the suggested immunmodulatory link in CP and may be a key mechanism in CP fibrogenesis and pain generation. Taken together, these novel findings suggest that MFG-E8 blockade may be a promising tool for future immunotherapy in CP to attenuate both fibrosis and pain sensation.

N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area.

Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.

Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

Energy metabolism and proliferation in pancreatic carcinogenesis.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer entity with a high proliferative potential. Uncontrolled cell proliferation is mediated by a number of core signaling pathways. Recently, novel data of PDAC biology suggest that these core signal pathways affect cell proliferation and metabolism simultaneously. METHODS: Here, we reviewed the literature on core metabolic signaling pathways in pancreatic carcinogenesis. RESULTS: Results obtained from mouse genetics and in vitro experiments have demonstrated the significance of the Kras, p53, c-Myc, and Lkb1 networks in the proliferation of pancreatic epithelial and cancer cells. At the same time, these major pathways also affect energy metabolism by influencing glucose and glutamine utilization. In particular, Kras-mediated metabolic changes seem to be directly involved in carcinogenesis. However, there is a lack of solid evidence on how metabolism and proliferation are connected in pancreatic carcinogenesis. CONCLUSION: Understanding early and subtle changes in cellular metabolism of pancreatic epithelial-and specifically of acinar-cells, which accompany or directly influence malignant transformation and uncontrolled proliferation, will be paramount to define novel imaging and other modalities for earlier detection of PDAC.

Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

The severity of neural invasion is a crucial prognostic factor in rectal cancer independent of neoadjuvant radiochemotherapy.

OBJECTIVE: To provide a comprehensive characterization of neural invasion (NI) in rectal adenocarcinoma (RC), to establish a novel NI-severity scoring system, and to assess the prognostic value of NI with emphasis on its localization and severity. BACKGROUND: The literature merely contains small-scale studies with limited histopathological characterization of NI in RC. METHODS: Neural invasion was thoroughly characterized in 296 patients with locally advanced uT3-RC (139 with primary resection and 157 with neoadjuvant radiochemotherapy [nRCTx]). To identify the precise localization of NI, we investigated the main tumor, peritumoral area, adjacent normal tissue, and all lymph nodes. To classify the clinical impact of NI, an NI severity score was established and related to patient prognosis. RESULTS: Neural invasion was detected in 32% of patients with primary resection and in 19% (P = 0.010) receiving nRCTx. The major location of NI was found in the peritumoral area. The prevalence of NI in the main tumor within the primary resection group was 6%, whereas it was absent in the nRCTx group (P = 0.002). Increasing NI severity, but not NI localization, was associated with a significantly poorer survival and increased local recurrence rate in both groups. Multivariate analysis (including TNM-stage, grading, and Carcinoembryonic antigen (CEA)) revealed NI prevalence and severity as independent prognostic factors. CONCLUSIONS: Neural invasion in RC has a heterogeneous appearance in regard to its localization and its severity. nRCTx seems to have a suppressive effect on NI. Neural invasion severity might be applied as a novel tool to estimate accurately patient's prognosis and thus should be considered in pathology reports.