Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis.

Background: The impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial. Methods: Two independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated. Results: Out of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61-1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21-1.74; p < 0.01) and lower rate of major histopathological response than non-SRCC patients (OR, 2.47; 95% CI, 1.78-3.44; p < 0.01). Conclusion: The current meta-analysis could not demonstrate beneficial effects of nCTX for SRCC patients. Histopathological response to and survival benefits of non-taxane-based nCTX seem to be lower in comparison to non-SRC esophagogastric cancer. However, certainty of evidence is low due to the scarcity of high-quality trials. Further research is necessary to determine optimal treatment for SRCC patients. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42022298743).

Endotracheal Intubation via Tracheotomy and Subsequent Thoracotomy in Rats for Non-Survival Applications.

Endotracheal intubation and subsequent ventilation are often basic requirements for translational research in rat models for various interventions that require controlled or high ventilation pressures or access to the thoracic cavity and organs. Conventional endoorotracheal intubation using the anatomically existing route through the mouth is well suited for survival experiments. However, this procedure poses some challenges, including generally higher levels of the required experience and technical skill, more advanced equipment, and greater time effort with relevant intubation failure rates and complications such as tracheal perforation, temporary systemic hypooxygenation, and relevant aerial leakage. This manuscript, therefore, presents a detailed step-by-step protocol for endotracheal intubation through tracheotomy in non-survival rat models when guaranteed intubation success, constant oxygenation levels, high ventilation pressures, or open thoracotomy are required. The protocol emphasizes the importance of meticulous surgical technique to ensure consistent and reliable outcomes, especially for researchers who are inexperienced or lack routine in the technique of endoorotracheal intubation via direct laryngoscopy. This procedure is, therefore, expected to minimize animal suffering and unnecessary animal losses.

Portal vein resection in pancreatic neuroendocrine neoplasms.

BACKGROUND: Surgery offers the only cure for borderline resectable or locally advanced pancreatic neuroendocrine neoplasms. Data on incidence, perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms are scarce. This study aimed to analyze the outcome and prognostic factors of portal vein resection in surgery for pancreatic neuroendocrine neoplasms. METHODS: Consecutive patients were analyzed. Portal vein resection was classified according to the International Study Group of Pancreatic Surgery. Clinicopathologic features and overall and disease-free survival were assessed and compared with standard resection in a matched-pair analysis. RESULTS: A total of 54 of 666 (8%) resected pancreatic neuroendocrine neoplasms patients underwent portal vein resection, including 7 (13%) tangential resections with venorrhaphy (type 1), 2 (4%) patch reconstructions (type 2), 35 (65%) end-to-end anastomoses (type 3), and 10 (19%) graft interpositions (type 4); 52% of those underwent pancreatoduodenectomy, 22% distal pancreatectomy, and 26% total pancreatectomy. Postoperative portal vein thrombosis occurred in 19%. Postoperative pancreatic fistula grades B and C (9% vs 16%; P = .357), complications Clavien-Dindo grade ≥IIIb (28% vs 13%; P = .071), and 90-day mortality rate (2% each) were not significantly different compared with 108 matched patients. The 5-year overall survival was 45% (standard resection: 68%; P = .432), and the 5-year disease-free survival was 25% (standard resection: 34%; P = .716). Radical resection was associated with 5-year overall survival of 51% and 5-year disease-specific survival of 75%. CONCLUSION: This is the largest single-center analysis evaluating perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms. The postoperative complication rate after portal vein resection is comparable with standard resection. The 90-day mortality is low. Radical resection leads to excellent 5-year oncological survival.

Retroperitoneoscopic adrenalectomy may be superior to laparoscopic transperitoneal adrenalectomy in terms of costs and profit: a retrospective pair-matched cohort analysis.

BACKGROUND: A direct comparison of the cost-benefit analysis of retroperitoneoscopic adrenalectomy (RPA) versus the minimally invasive transperitoneal access (LTA) approach is currently lacking. We hypothesized that RPA is more cost effective than LTA; promising significant savings for the healthcare system in an era of ever more limited resources. METHODS: We performed a monocentric retrospective observational cohort study based on data from our Endocrine Surgery Registry. Patients who were operated upon between 2019 and 2022 were included. After pair-matching, both cohorts (RPA vs. LTA) were compared for perioperative variables and treatment costs (process cost calculation), revenue and profit. RESULTS: Two homogenous cohorts of 43 patients each (RPA vs. LTA) were identified following matching. Patient characteristics between the cohorts were comparable. In terms of both treatment-associated costs and profit, the RPA procedure was superior to LTA (costs: US$5789.99 for RPA vs. US$6617.75 for LTA, P = 0.043; profit: US$1235.59 for RPA vs. US$653.33 for LTA, P = 0.027). The duration of inpatient treatment and comorbidities significantly influenced the cost of treatment and the overall profit. CONCLUSIONS: RPA appears not only to offer benefits over LTA in terms of perioperative morbidity and length of hospital stay, but also has a superior financial cost/benefit profile.

Combined non-alcoholic fatty liver disease and type 2 diabetes in severely obese patients-medium term effects of sleeve gastrectomy versus Roux-en-Y-gastric bypass on disease markers.

Background: We aimed to evaluate the medium-term efficacy of sleeve gastrectomy (SG) vs. Roux-en-Y gastric bypass (RYGB) on remission of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Methods: We identified severely obese patients [body mass index (BMI) >35 kg/m2] with NAFLD (as defined by the Longitudinal Assessment of Bariatric Surgery Study) and T2DM (as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology) who underwent SG or RYGB in a single university surgical centre. The cohorts were match-paired and data were analysed after at least 3 years of follow up. The key outcomes measured were: (I) the improvement of liver function tests and NAFLD markers; (II) glycemic control and insulin resistance. Results: Ninety-six patients were investigated; 44 (45.8%) were women. The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m2 in the RYGB group. SG and RYGB both significantly reduced serum liver enzyme concentrations. NAFLD markers resolved 2 years after SG in all patients. In contrast, only 78% and 80% of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively. Both procedures resulted in comparable rates of remission of T2DM. Conclusions: Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities. However, our results need to be confirmed in prospective trials. Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.

Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis.

The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001−2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95−170) versus 263 (172−337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7−11) versus 10 (8−17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.

Endoscopic Stent Placement Can Successfully Treat Gastric Leak Following Laparoscopic Sleeve Gastrectomy If and Only If an Esophagoduodenal Megastent Is Used.

PURPOSE: Gastric staple line leakage (GL) is a serious complication of laparoscopic sleeve gastrectomy (LSG), with a specific mortality ranging from 0.2 to 3.7%. The current treatment of choice is stent insertion. However, it is unclear whether the type of stent which is inserted affects treatment outcome. Therefore, we aimed not only to determine the effectiveness of stent treatment for GL but also to specifically clarify whether treatment outcome was dependent on the type of stent (small- (SS) or megastent (MS)) which was used. PATIENTS AND METHODS: A single-centre retrospective study of 23 consecutive patients was conducted to compare the outcomes of SS (n = 12) and MS (n = 11) for the treatment of GL following LSG. The primary outcome measure was the success rate of stenting, defined as complete healing of the GL without changing the treatment strategy. Treatment change or death were both coded as failure. RESULTS: The success rate of MS was 91% (10/11) compared to only 50% (6/12) for SS (p = 0.006). An average of 2.3 ± 0.5 and 6.8 ± 3.7 endoscopies were required to achieve healing in the MS and SS groups respectively (p < 0.001). The average time to resumption of oral nutrition was shorter in the MS group (1.4 ± 1.1 days vs. 23.1 ± 33.1 days, p = 0.003). CONCLUSIONS: Stent therapy is only effective and safe for the treatment of GL after LSG if a MS is used. Treatment with a MS may not only increase treatment success rates but may also facilitate earlier resumption of oral nutrition and shorten the duration of hospitalization.

Anatomical framework for pre-operative planning of laparoscopic left-sided colorectal surgery: Potential relevance of the distance between the inferior mesenteric artery and inferior mesenteric vein.

BACKGROUND: The medial-to-lateral approach is favored by most colorectal surgeons for laparoscopic retroperitoneal dissection and mobilisation of the left colon. The peritoneal access window, i.e. the distance between the inferior mesenteric vein (IMV) and inferior mesenteric artery (IMA) must be large enough to perform the procedure safely and successfully. However, studies investigating the IMA-IMV distance and factors affecting this variable, are scarce. Therefore, we examined the IMA-IMV and D3-IMA distances to determine an anatomical framework on planning and adapting surgical therapy. BASIC PROCEDURES: The IMA-IMV and D3-IMA distances were retrospectively measured in 230 patients (127 Male/103 Female, Median Age=54.5) who had undergone pre-operative CT-scanning before laparoscopic left-sided colorectal surgery. Two observers rated the images and interrater reliability was calculated. Subgroup, simple and multiple linear regression analyses were performed in order to detect potential interaction between morphometric variables and IMA-IMV distance. MAIN FINDINGS: We demonstrated a significant correlation between the inferior margin of the duodenum and the origin of IMA. Determination of the IMA-IMV distance was simple and reproducible. Approximately 45% of patients undergoing laparoscopic colorectal procedures had a narrow distance (≤50mm). There was a sexual dimorphism in IMA-IMV distance, being consistently large in males. There were no other pre-operative factors which predicted whether the peritoneal dissection window for a medial-to-lateral approach was sufficient. CONCLUSIONS: Our results provide new data for a better understanding of metric variations in abdominal vascular structures and complement previous observations. In view of our results, we recommend pre-operative measurement of the IMA-IMV before colorectal surgery where the medial-to-lateral approach is planned. Given that a narrow distance may predict a difficult dissection, this factor should be taken into account to determine the optimal surgical approach in each patient.

Minimally invasive partial versus total adrenalectomy for unilateral primary hyperaldosteronism-a retrospective, multicenter matched-pair analysis using the new international consensus on outcome measures.

BACKGROUND: Primary hyperaldosteronism is a recognized risk factor for myocardial infarction, stroke, and atrial fibrillation. Minimally invasive adrenalectomy is the first-line treatment for localized primary hyperaldosteronism. Whether minimally invasive adrenalectomy should be performed using a cortex-sparing technique (partial minimally invasive adrenalectomy) or not (total minimally invasive adrenalectomy) remains a subject of debate. The aim of our study was to evaluate the clinical and biochemical efficacy of both procedures and to examine the morbidity associated with partial minimally invasive adrenalectomy versus total minimally invasive adrenalectomy in a multicenter study. METHODS: Using a retrospective study design, we determined the efficacy, morbidity, and mortality of partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy. The Primary Aldosteronism Surgical Outcome Study classification was used to explore clinical and biochemical success. Matched-pair analysis was used in order to address possible bias. RESULTS: We evaluated 234 matched patients with unilateral primary hyperaldosteronism: 78 (33.3%) underwent partial minimally invasive adrenalectomy, and 156 (66.7%) were treated with total minimally invasive adrenalectomy. Complete clinical success was achieved in 40.6%, and partial clinical success in an additional 52.6% of patients in the entire cohort. Complete biochemical success was seen in 94.0% of patients. Success rates and the incidence of perioperative complications were comparable between groups. Both postoperative hypocortisolism (11.5% vs 25.0% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy, respectively; P < .001) and postoperative hypoglycemia (2.6% vs 7.1% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy; P = .039) occurred more frequently after total minimally invasive adrenalectomy. CONCLUSION: Our study provides evidence that patients with unilateral primary hyperaldosteronism are good surgical candidates for partial minimally invasive adrenalectomy. Not only is the surgical outcome comparable to that of total minimally invasive adrenalectomy, but also postsurgical morbidity, particularly in terms of hypocortisolism and hypoglycemia, may be reduced.

Insufflation pressure above 25 mm Hg confers no additional benefit over lower pressure insufflation during posterior retroperitoneoscopic adrenalectomy: a retrospective multi-centre propensity score-matched analysis.

BACKGROUND: Insufflation pressures of or in excess of 25 mm Hg CO2 are routinely used during posterior retroperitoneoscopic adrenalectomy (PRA) in most centres. A critical analysis of the surgical literature provides limited evidence to support this strategy. OBJECTIVE: To determine whether high pressure (≥ 25 mm Hg) compared with lower pressure (< 25 mm Hg) retroperitoneoscopy reduces operating time and complications. METHODS: A multi-centre retrospective cohort study was performed using data collected over a period of almost one decade (1st November 2008 until 1st February 2018) from surgical centres in Germany. A total of 1032 patients with benign adrenal tumours were identified. We compared patients undergoing PRA with insufflation pressures of < 25 mm Hg (G20 group) versus ≥ 25 mm Hg (G25 group). A propensity score matching analysis was performed using BMI, tumour size and surgeon's experience as independent variables. The main outcomes were (1) the incidence of perioperative complications and (2) the length of operating time. RESULTS: The baseline patient characteristics were similar in both groups, with the exception of tumour size, BMI and surgeon's experience in PRA. After propensity score matching, perioperative outcomes, especially perioperative complications (3.7% vs. 5.5% in G20 and G25, respectively; p = 0.335) and operation duration (47 min vs. 45 min in G20 and G25, respectively; p = 0.673), did not significantly differ between the groups. CONCLUSION: Neither patient safety nor operative success was compromised when PRA was performed with insufflation pressures below 25 mm Hg. Prospective studies are required to determine whether an optimal insufflation pressure exists that maximizes patient safety and minimizes the risks of post-surgical complications. Nevertheless, our results call for a careful re-evaluation of the routine use of high insufflation pressures during PRA. In the absence of prospective data, commencing PRA with lower insufflation pressures, with the option of increasing insufflation pressures to counter intraoperative bleeding or exposition difficulties, may represent a reasonable strategy.

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa-Light at the End of the Microbiological Tunnel.

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)-also known as acne inversa-a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.

The reporting of race and/or ethnicity in the medical literature: a retrospective bibliometric analysis confirmed room for improvement.

OBJECTIVES: Although the collection of race and/or ethnicity data is an important way to identify and address inequalities in health care provision and disparities in access to treatment, studies examining the extent to which race and/or ethnicity data are reported in the medical literature, and the quality of these data, are lacking. Therefore, we sought to objectively determine the quality of reporting of race and/or ethnicity in original medical research papers. STUDY DESIGN AND SETTING: A retrospective bibliometric analysis was used. Two independent investigators analyzed original articles investigating race/ethnicity, published between 2007 and 2018, in the 10 top-ranking academic journals in each of the following categories: general medicine, surgery, and oncology. RESULTS: A total of 995 original articles were included in our analysis. Only 45 studies (4.52%) provided a formal definition of race/ethnicity, and 8.94% identified the investigator responsible for the classification. While race/ethnicity was a key part of study design in 31.86% of the included investigations, the method used to classify individuals into racial/ethnic groups was described in only 10.25% of articles. In terms of terminology, we identified 81 different race/ethnicity classifications, but these were often imprecise and open to interpretation. CONCLUSION: There is significant room for improvement in the collection, reporting, and publishing of data describing ethnicity and/or race in the medical literature.

MicroRNA analysis of gastroenteropancreatic neuroendocrine tumors and metastases.

The incidence of neuroendocrine neoplasias (NEN) continues to increase. Since the primary tumor cannot be diagnosed in some cases of metastatic disease, new biomarkers are clearly needed to find the most probable site of origin. Tissue samples from 79 patients were analyzed and microRNA profiles were generated from a total of 76 primary tumors, 31 lymph node and 14 solid organ metastases. NEN metastases were associated with elevated levels of miR-30a-5p, miR-210, miR-339-3p, miR-345 and miR-660. Three microRNAs showed a strong correlation between proliferation index and metastatic disease in general (miR-150, miR-21 and miR-660). Further, each anatomic location (primary or metastatic) had one or more site-specific microRNAs more highly expressed in these tissues. Comparison between primary tumors and metastases revealed an overlap only in pancreatic (miR-127) and ileal tumors (let-7g, miR-200a and miR-331). This thorough analysis of gastroenteropancreatic neuroendocrine tumors demonstrates site-specific microRNA profiles, correlation with proliferation indices as well as corresponding nodal and distant metastases. Using microRNA profiling might improve NEN diagnostics by linking metastases to a most probable site of origin.

MANAGEMENT OF ENDOCRINE DISEASE: Which metabolic procedure? Comparing outcomes in sleeve gastrectomy and Roux-en Y gastric bypass.

Obesity and its associated comorbidities have become one of the largest challenges for health care in the near future. Conservative therapy for obesity and related comorbidities has a very high failure rate and poor long-term results. Similarly, the conservative and medical management of the majority of metabolic diseases such as type 2 diabetes mellitus are only able to slow down disease progression but have no causal effect on the disease process. Obesity surgery has evolved as a highly effective therapy for severe obesity achieving long-lasting weight loss. Furthermore, several studies have demonstrated the beneficial effects of obesity surgery on reduction of overall mortality, reduction of cardiovascular events and superior control of obesity-related diseases such as type 2 diabetes mellitus, dyslipidemia and also the non-alcoholic steatohepatitis compared to medical therapy. Based on these findings, the term 'metabolic surgery' with the focus on treating metabolic diseases independent of body weight has been coined. Of great interest are recent studies that show that even existing complications of metabolic diseases such as diabetic nephropathy or the non-alcoholic steatohepatitis can be reversed by metabolic surgery. Although metabolic surgery has proven to be a safe and effective treatment for obesity, resolution of comorbidities and enhancing quality of life, it is still uncertain and unclear, which surgical procedure is the most effective to achieve these metabolic effects. The aim of this review is to compare the effects of the two currently most widely used metabolic operations, the Roux-en-Y gastric bypass and the sleeve gastrectomy in the treatment of obesity and its related comorbidities.

Histopathological tumor invasion of the mesenterico-portal vein is characterized by aggressive biology and stromal fibroblast activation.

BACKGROUND: Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology. METHODS: Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database. Immunohistochemical staining of tumor tissue was performed for the markers of epithelial-mesenchymal transition (EMT) E-Cadherin, Vimentin and beta-Catenin. Morphology of cancer-associated fibroblasts (CAFs) was assessed as inactive or activated. Statistical calculations were performed with MedCalc software. RESULTS: In total, 41 patients could be included. Median overall survival was 25 months. PVI was found in 17 patients (41%) and was significantly associated with loss of membranous E-Cadherin in tumor buds (p = 0.020), increased Vimentin expression (p = 0.03), activated CAF morphology (p = 0.046) and margin positive resection (p = 0.005). CONCLUSION: Our findings suggest that PVI is associated with aggressive tumor biology and disseminated growth less amenable to margin-negative resection.

Expression Pattern of CDX2, Estrogen and Progesterone Receptors in Primary Gastroenteropancreatic Neuroendocrine Tumors and Metastases.

BACKGROUND: A significant number of patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs) present with metastatic disease and with unknown primary in about 15% of cases. MATERIALS AND METHODS: We analyzed 163 primaries of GEP NET and 115 metastases for expression of caudal type homebox 2 (CDX2), estrogen receptor (ER), progesterone receptor (PR), somatostatin receptor 2a (SSTR2a) and Ki67. RESULTS: PR was most often positive in pancreatic NET and only rarely in non-pancreatic NET (p<0.001). ER was more frequently expressed in non-pancreatic NET (p<0.001) and was more often positive in females than males (p=0.019). CDX2 was positive in all primaries of the duodenum, ileum and appendix, but was also detected in 24% of metastases with pancreatic primary. SSTR2a and Ki67 did not differ significantly between primaries and metastases. CONCLUSION: Our data substantiate the value of PR, ER and CDX2 in GEP NET, and steroid hormone receptors, being differentially expressed in male and female patients. Differences between primaries and metastases were small but potentially relevant.

Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant hereditary disorder associated with the development of endocrine tumors due to reduced expression of the tumor suppressor protein menin. Recent studies indicate a general role of menin in carcinogenesis, affecting the prevalence and clinical course of common non-endocrine tumors such as breast cancer, hepatocellular carcinoma and melanoma. Here we report a new germline missense mutation of Men1 in a German family with atypical tumor phenotype over three generations. Based on the type of mutation, we discuss possible changes in menin function leading to atypical tumorigenesis and present the clinical significance of such findings. CASE PRESENTATION: A German family with a history of primary hyperparathyroidism presented to our Hospital for further evaluation. Members of the family demonstrated many different atypical tumors, such as renal cell carcinoma, papillary thyroid cancer and prostate cancer. DNA sequencing from peripheral blood revealed a novel mutation: Ser38Cys [TCC>TGC] in exon 2, codon 38 of Men1. This novel mutation is located in a region of menin which is responsible for interactions with the transcription factor JunD. This factor has recently been associated with prostate cancer. DNA sequencing of two of the atypical tumors (prostate cancer, papillary thyroid cancer) did not reveal a loss of heterozygosity, indicating an impact on menin expression and function in the heterozygous state, in line with results in +/-Men1 mutant mice developing prostate cancer. CONCLUSION: The results and clinical course of disease in this case indicate the potential role of menin in the development of non-endocrine or atypical-endocrine tumors in MEN1 patients. Further investigations are needed to clarify both the general role of menin and the importance of specific mutations in carcinogenesis. Nevertheless, in families with uncommon manifestations of the syndrome early diagnostic adjustments should be considered.

Reduction of Acute Shoulder Dislocations in a Remote Environment: A Prospective Multicenter Observational Study.

OBJECTIVE: Acute dislocations of the glenohumeral joint are common in wilderness activities. Emergent reduction should take place at the site of trauma to reduce the patient's pain and the risk of vascular and neurological complications. A limited number of reduction methods are applicable in remote areas. The aim of this study is to present our method of reduction of anterior shoulder luxation that is easily applicable in remote areas without medication, adjuncts, and assistants and is well tolerated by patients. METHODS: A prospective observational study was conducted during a 5-year period. The patients included underwent closed manual reduction with our technique. After each reduction, the physician who performed the reduction completed a standardized detailed history, and reexamined the patient (for acute complications). The patients were contacted 6 months after the trauma to investigate long-term postreduction complications. RESULTS: Reduction was achieved with our method in 39 (100.0%) of 39 patients. The mean pain felt during our reduction procedure was rated 1.7 ± 1.4 (on a scale of 10) using the visual analog scale scoring system. No complications were noted before or after the reduction attempts. We did not find any long-term complications. CONCLUSIONS: The reduction method presented in the present study is an effective method for the reduction of acute shoulder luxations in remote places. Our data suggest that this method could be applied for safe and effective reduction of shoulder dislocation.