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Here we tested whether global histone modifications predict survival in organic hyperinsulinism and whether global histone modification pattern can be used to distinguish benign from malignant primary insulinoma. A tissue microarray (TMA) was built, using samples from 63 patients with organic hyperinsulinism. The TMA was classified according to the WHO classification of 2004 [WHO 1A: benign insulinoma (wdPET); WHO 1B: unknown behavior (wdPETub); WHO 2/3: malignant insulinoma (wdPEC/pdPEC)]. The TMA consisted of tissue cores from islands of Langerhans, primary insulinomas, lymph node metastases, and hepatic metastases. Immunohistochemistry was performed on consecutive TMA slides with antibodies against H3K9Ac, H3K18Ac, H4K12Ac, H3K4diMe, and H4R3diMe. The Remmele immunoreactive scoring system was used to classify the staining. The IHC staining results were correlated to the WHO-classification of 2004 as well as to clinical follow-up data (mean: 107 months; range: 1-312 months). A nuclear staining pattern was observed for all antibodies directed against histone H3 and H4 acetylation/methylation sites. We observed significant differences in the distribution of the medians across all investigated tissue types (H3K9Ac, p = 0.004; H3K18Ac, p = 0.001; H4K12Ac, p = 0.006; H4R3diMe, p = 0.002) except for H3K4diMe (p = 0.183). Correlation of the histone modification with the WHO-classification and clinical follow-up data, showed in the dichotomized groups ["low" (score 0-3), "moderate" (4-7) vs. "high" ( ⩾ 8)] that patients with lower H3K18Ac levels ("low + moderate") had a significantly decreased relapse-free survival vs. patients with high H3K18Ac levels (p = 0.038). The WHO classification and age were also of significant prognostic impact upon univariate analysis. A backwards Cox proportional hazards model revealed the independent prognostic effekt of H3K18Ac levels. Our data revealed low K18 acetylation levels of histone H3 as independent prognostic factor in organic hyperinsulinism. This result warrants validation with independent data sets of organic hyperinsulinism, but is in line with several previous studies in different cancer entities. The broad applicability of this potential biomarker might lead to standardized diagnostic tests in near future and may help to manage insulinoma patients more effectively. [ABSTRACT FROM AUTHOR]

Abstract Background In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3) maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Eph B3 in esophageal adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin in both the healthy esophagus and in Barrett’s carcinoma. Methods Simultaneous expression of Eph B3 and E-cadherin was investigated in samples from 141 patients with Barrett’s carcinoma and from 20 healthy esophagi using immunhistology and quantitative PCR. Results from healthy squamous epithelium, Barrett’s metaplasia and staging-specific esophageal adenocarcinoma were correlated. Results A significantly reduced E-cadherin mRNA expression could be detected in adenocarcinoma compared to dysplasia. The immunhistological activity of E-cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when the Eph receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed a significant inverse correlation to tumor stage. Conclusions We present novel evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma sequence, the infiltrative growth pattern and the development of lymph node metastases.

Purpose: One of the major challenges in the management of patients with septic and non-septic open abdomen (OA) is to control abdominal wall retraction. The aim of this study was to evaluate the impact of a novel vertical traction device (VTD) on primary fascial closure (PFC) and prevention of fascial retraction., Methods: Twenty patients treated with OA were included in this retrospective multicenter study. All patients were initially stabilized with laparostomy and the abdomen temporarily sealed either with a Bogotá bag or a negative pressure wound therapy system (NPWT)., Results: The mean duration of OA and fascia-to-fascia distance (FTF) prior to the VTD application were 3 days and 15 cm, respectively. At relook laparotomy 48 h after VTD implementation, the mean FTF distance significantly decreased to 10 cm (p = 0.0081). In all cases, PFC was achieved after a mean period of 7 days. Twelve patients received the VTD in combination with a NPWT, whereas in eight patients, the device was combined with an alternative temporary abdominal closure system (TAC). Although not statistically significant, the FTF distance remarkably decreased in both groups at relook laparotomy 48 h following the device implementation. The mean periods of PFC for patients with septic and non-septic OA were comparable (7.5 vs. 7 days). During follow-up, two patients developed an incisional hernia., Conclusion: Vertical traction device prevents fascial retraction and facilitates early PFC in OA. In combination with NPWT, rapid fascial closure of large abdominal defects can be achieved., (© 2022. The Author(s).)

To implement typical doses (TD) and typical values (TV) for fluoroscopic diagnostic and interventional procedures. A total of 3811 fluoroscopic procedures performed within 34 months on three devices were included in this retrospective study. Dose-, patient- and procedure-related information were extracted using the institutional dose management system (DMS). TD/TV were defined as median dose and calculated for the five most frequent procedures per device for dose area product (DAP), cumulative air kerma (CAK) and fluoroscopy time (FT). National diagnostic reference levels and other single facility studies were compared to our results. Additionally, the five procedures with the highest doses of each device were analysed. To evaluate the data coverage of the DMS compared to the picture archiving and communication system (PACS), procedure lists were extracted from the PACS and compared to the procedure information extracted from the DMS. TD/TV for 15 procedures were implemented. Among all devices, TD for DAP ranged between 0.6 Gycm 2 for port catheter control ( n = 64) and 145.9 Gycm 2 for transarterial chemoembolisation ( n = 84). TD for CAK ranged between 5 mGy for port catheter control and 1397 mGy for aneurysm treatment ( n = 129) and TV for FT ranged between 0.3 min for upper cavography ( n = 67) and 51.4 min for aneurysm treatment. TD for DAP and CAK were lower or within the range of other single facility studies. The five procedures with the highest median DAP per device were identified, 6 of 15 procedures were also found to be among the most frequent procedures. Data coverage of the DMS compared to the PACS ranged between 71% (device 2, stroke treatment) and 78% (device 1, lower limb angiography) for the most common procedure per device. Thus, in 22%-29% of cases dose data of the performed procedure was not transferred into the DMS. We implemented TD/TV for fluoroscopic diagnostic and interventional procedures which enable a comprehensive dose analysis and comparison with previously published values., (Creative Commons Attribution license.)

Surgical therapy for adenocarcinoma of the esophagogastric junction II requires distal esophagectomy, in which a transhiatal management of the lower esophagus is critical. The 'dorsal track control' (DTC) maneuver presented here facilitates the atraumatic handling of the distal esophagus, in preparation for a circular-stapled esophagojejunostomy. It is based on a ventral semicircular incision in the distal esophagus, with an intact dorsal wall for traction control of the esophagus. The maneuver facilitates the proper placement of the purse-string suture, up to its tying (around the anvil), thus minimizing the manipulation of the remaining esophagus. Furthermore, the dorsally-exposed inner wall surface of the ventrally-opened esophagus serves as a guiding chute that eases anvil insertion into the esophageal lumen. We performed this novel technique in 21 cases, enabling a safe anastomosis up to 10 cm proximal to the Z-line. No anastomotic insufficiency was observed. The DTC technique improves high transhiatal esophagojejunostomy., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Korean Gastric Cancer Association.)

Purpose: To analyse technical success, complications, and short- and intermediate-term outcomes after heparin-bonded stent graft implantation for the treatment of major abdominal vessel injury after upper abdominal surgery., Methods: This retrospective, IRB-approved analysis included 29 consecutive patients (female: n = 6, male: n = 23, mean age 65.9 ± 11.2 years). All patients underwent angiography and attempted heparin-bonded stent-graft implantation because of a major visceral arterial injury after upper abdominal surgery. Electronic clinical records, angiographic reports and imaging datasets were reviewed to assess technical success and complications. Telephone interviews were performed to obtain follow-up information and to estimate short- (> 30 days) and intermediate-term (> 90 days) outcomes., Results: Successful stent graft placement was achieved in 82.8% (24/29). Peri-interventional complications were observed in 20.7% (6/29) and delayed, angiography-associated complications were observed in 34.5% (10/29) of the patients. Symptomatic re-bleeding occurred in 24.1% (7/29). Short-term survival (> 30 days) was 72.4% (21/29). Intermediate survival (> 90 days) was 37.9% (11/29)., Conclusion: Treatment of major vascular injuries with heparin-bonded stent grafts is feasible with a high technical success rate. However, survival depends on the underlying surgical condition, making interdisciplinary patient management mandatory., Key Points: • Stent graft implantation is challenging, but has a high technical success rate. • Complications are frequent but surgical conversion is rarely necessary. • Survival depends on the underlying surgical condition causing the vascular injury. • Interdisciplinary management is crucial for the survival of these patients.

Introduction: Tumoral calcinosis (TC) is a rare disorder defined by hyperphosphatemia and ectopic calcifications in various locations. The most common form of TC is associated with disorders such as renal insufficiency, hyperparathyroidism, or hypervitaminosis D. The primary (hereditary) TC is caused by inactivating mutations in either the fibroblast growth factor 23 (FGF23), the GalNAc transferase 3 (GALNT3) or the KLOTHO (KL) gene., Presentation of Case: We report here a case of secondary TC in end-stage renal disease. The patient was on regular hemodialysis and presented with severe painful soft-tissue calcifications around her left hip and shoulder that had been increasing over the last two years. Initially, she was treated with dietary phosphate restriction and phosphate binders. Because of high phosphate blood levels, which were not yet managed with dialysis and medical therapy, a subtotal parathyroidectomy (sP) was performed. This approach demonstrated significant response. Three months after surgery a rapid regression of the tumors was observed., Disscusion: Regardless of the etiology, the two types of TC do not differ in their radiologic or histopathologic presentations but need to be diagnosed correctly to initiate targeted and effective treatment. Considering the primary TC, primary treatment is early and complete surgical excision. In case of secondary TC surgical excision of the tumoral masses should be avoid because of extensive complications. These patients benefit from sP., Conclusion: After initial conservative therapy chronic kidney disease patients with TC might benefit from sP to avoid prolonged suffering and potential mutilations., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: There is evidence for the prognostic value of perioperative blood transfusion in the surgical treatment of patients with rectal cancer in the current literature. Also preoperative anaemia seems to have an impact on the outcome of these patients. The aim of this study was to evaluate the impact of preoperative anaemia and perioperative blood transfusion in patients with rectal cancer treated in our hospital., Patients and Methods: 208 patients (81 females, 127 males; median age, 67 years) with rectal cancer were included in this retrospective study. All patients received surgical treatment. In 75 % of the patients an anterior rectum resection was performed while 25 % received an abdominoperineal rectum exstirpation. Patients with neoadjuvant treatment were included and statistical analyses were performed., Results: 107 (51.4 %) patients exhibited preoperative anaemia. Patients with neoadjuvant treatment presented with significantly lower preoperative Hb (haemoglobin) values than patients without neoadjuvant treatment (p = 0.022). Patients with preoperative anaemia received significantly more blood transfusions (p = 0.001), had significantly longer hospital stays (p = 0.023) and significantly lower 5-years overall survival (p = 0.005). Blood transfusion was necessary in 82 patients (39.4 %). These patients presented with a significantly higher rate of perioperative complications (p = 0.01) and a lower 5-years overall survival (p = 0.002). In multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor., Conclusion: In our study preoperative anaemia and perioperative blood transfusion seems to have an impact on outcome of surgical treatment of patients with rectal cancer. However, in multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor., (Georg Thieme Verlag KG Stuttgart · New York.)

We report the case of a 25-year-old male with Neurofibromatosis type I (NF-1), who presented at the time of admission with clinical findings of an acute abdomen caused by a mechanical obstruction. Computerized tomography showed a volvulus of the terminal ileum with mesenteric swirling as the cause of the patient's symptoms. Consecutive exploratory laparotomy confirmed the diagnosis and 70 cm of the small intestine was resected due to an affection of the mesentery by multiple neurofibromas. The gastrointestinal tract is affected in approximately 10% of patients with NF-1, however the mesentery is almost always spared. Here we describe the unique case of a patient with a volvulus caused by mesenteric manifestation of von Recklinghausen's disease, emphasizing the role of surgery in a team of multidisciplinary specialists to treat this multiorganic disease.

Here we evaluated the prevalence and prognostic impact of epithelial cell adhesion molecule (EpCAM)-positive disseminated tumor cells (DTCs) in stage I rectal cancer. Further we tested the association of these single tumor cells or small tumor cell groups with the extent of peritumoral lymphangiogenesis. A total of 845 regional lymph nodes (LN) of 44 patients classified as negative on conventional histopathology were retrospectively reanalyzed with immunohistochemistry (IHC) using the monoclonal antibody Ber-Ep4 directed against EpCAM for the detection of DTCs. The degree of lymphangiogenesis in the primary tumors was assessed by IHC of the primary tumor tissue using the monoclonal antibody D2-40, which reacts with the lymphatic endothelium. The IHC results were correlated with clinico-pathologic parameters and clinical follow-up data. EpCAM-positive DTCs in LNs were detected in 8 (18.2%) of the 44 patients. During a median follow-up of 59 months, 3 (37.5%) of the 8 patients with EpCAM-positive DTCs relapsed, whereas none of the DTC-negative patients developed tumor recurrence (P=0.004). Survival analysis revealed a significant effect of the prevalence of DTCs on overall survival (P=0.0009) and on recurrence-free survival (P=0.0001). Finally, the prevalence of EpCAM-positive DTCs in perirectal LNs was significantly correlated with a high density of peritumoral lymphatic vessels (P=0.015). Our results show that DTCs may occur in stage I of rectal cancer and are associated with poor prognosis. Their occurrence seems to be linked to a high density of newly formed lymphatic vessel at the primary tumor site. According to our data, patients with DTCs in their LN might benefit from adjuvant therapy.

Objective: Rectovaginal fistulae (RVF) are a serious and debilitating problem for patients and a challenge for the treating surgeons. We present our experiences in the surgical treatment of these patients., Methods: Study population consisted of 22 consecutive patients (range 26-70 years) with RVF treated in our department between 2003 and 2009. 13 RVF were observed after colorectal or gynaecological surgery, 3 occurred after radiotherapy, 2 due to tumour infiltration, 4 because of local inflammation (3x diverticultis, 1x ulcus simplex recti). The RVF was classified in all patients before treatment as either 'low' or 'high'., Results: Local procedures (transvaginal excision, preanal repair) as initial treatment were performed in 9 patients with low fistula. In 13 cases with high fistula an abdominal approach was performed to close the fistula. A recurrence was observed in 8/22 cases (36%), which were treated by a gracilis flap (n=2), a bulbospongiosus composite (n=1), a second abdominal approach (n=4), and a re-local excision (n=1). Ultimatively, in 19 cases the defect healed but in 3 patients the RVF persisted., Conclusions: Most important predictor of healing/failure is etiology followed by localization and recurrence of the RVF. Local (preanal, transvaginal) procedures are suitable for low RVF, whereas abdominal surgery is necessary in high RVF. In recurrent RVF, muscle flaps are promising procedures.

Cytochrome P450 epoxygenases (CYP450) have been recently shown to promote malignant progression. Here we investigated the mRNA and protein expression and potential clinical relevance of CYP2C9 in esophageal cancer. Highest expression was detected in esophageal adenocarcinoma (EAC; n=78) and adjacent esophageal mucosa (NEM; n=79). Levels of CYP2C9 in EAC and NEM were significantly higher compared to esophageal squamous cell carcinoma (ESCC; n=105). Early tumor stages and well-differentiated tumors showed a significantly higher CYP2C9 expression compared to progressed tumors. Moreover, CYP2C9 expression was correlated to high Ki-67 labeling indices in EAC and Ki-67 positive tumor cells in EAC and ESCC. Selective inhibition of CYP2C9 decreased tumor cell proliferation (KYSE30, PT1590 and OE19) in vitro, which was abolished by 11,12-epoxyeicosatrienoic acid (11,12-EET). Cell-cycle analysis using FACS revealed that inhibition of CYP2C9 leads to a G0/G1 phase cell-cycle arrest. CYP2C9 seems to be relevant for early esophageal cancer development by promoting tumor cell proliferation. Pharmacological inhibition of CYP2C9 might contribute to a more efficient therapy in CYP2C9 highly expressing esophageal cancers., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Rectovaginal fistuale (RVF) are a serious and disabling problem for the patients and a surgical challenge for the treating physicians. The most common causes of RVF are postoperative complications, inflammatory bowel disease, complications of radiotherapy, obstetric complications, and neoplasia. Therapeutic options are diverse and results often unsatisfactory. This article presents the treatment of patients with rectovaginal fistulae in the general surgery department of University Hospital in Duesseldorf, Germany. The therapeutic strategy for treatment of RVF is divided according to aetiology, localisation, and comorbidity. A diverting ileostomy is particularly useful if acute inflammation exists. Secondary repair may then be a better option. An initial approach with a local repair by preanal repair is justified in low RVF. For failures muscle flaps are promising., (Georg Thieme Verlag Stuttgart ˙ New York.)