Epithelioid hemangioendothelioma of the retroperitoneum - a rare vascular tumor.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor, affecting the liver, the lungs and the bones most frequently. It has a heterogenous clinical presentation and there is no consensus on optimal treatment. This report aims to present a rare case of a retroperitoneal EHE and to discuss on proper management.

Mega-megacolon: a case report.

PURPOSE: Large bowel obstruction and megacolon formation secondary to complicated diverticulitis is rare. METHODS: We present a case of an 84-year-old woman surviving large bowel obstruction and mega-megacolon formation secondary to complicated diverticulitis, with an impressive presentation of abdominal distention. RESULTS: The patient's symptoms, laboratory test results, and imaging were consistent with large bowel obstruction. The patient underwent urgent exploratory laparotomy. Upon entry in the abdomen, it was unexpected that the extreme colonic wall thickening had prevented perforation, indicating the longtime course of illness. The biopsy of the specimen from the site of the obstruction demonstrated an inflammatory obstructing mass. CONCLUSION: This report aims to point out the atypical and in-extremes presentation of an otherwise common disease.

Vascular complications during transcatheter aortic valve implantation: The role of the vascular surgeon.

INTRODUCTION: This study compares the incidence of vascular complications and other major outcomes between patients undergoing transcatheter aortic valve implantation, with and without a standardized preoperative vascular surgeon consultation. METHODS: This retrospective study evaluated all patients scheduled for transcatheter aortic valve implantation during a five-year period at a Hellenic University Hospital. Two main periods were evaluated: Group A (early period (2014-2015), without a standardized preoperative vascular surgeon consultation) and Group B (late period (2016-2018), with a standardized preoperative vascular surgeon consultation). All vascular complications as well as other major outcomes (early death, stroke, myocardial infarction, and treatment) were recorded. Univariate and multivariate analyses were also conducted. RESULTS: Overall, 382 transcatheter aortic valve implantation procedures were conducted (Group A: n = 115; duration = 19 months; Group B: n = 267; duration = 41 months). Overall, 58 vascular complications were recorded (21 patients in Group A and 37 patients in Group B (18.3% versus 13.9%; P = 0.279)). However, vascular complications that necessitated a vascular surgeon's interference were more frequent during the first period (13% versus 4.9%; P = 0.009). Among patients with a vascular complication, early mortality was higher during the first period (14.3% versus 0%; P = 0.034) although stroke and myocardial infarction rates were similar. Age >80 years (OR = 1.856 [1.134-3.452]; P = 0.03) and preoperative vascular surgeon consultation (OR = 0.345 [0.132-0.756]; P = 0.015) were the only independent predictors for vascular complications. CONCLUSIONS: A standardized preoperative evaluation by a vascular surgeon may decrease the risk for vascular complications that necessitate a repair as well as early mortality among patients undergoing transcatheter aortic valve implantation procedures.

The emerging role of microdialysis in diabetic patients undergoing amputation for limb ischemia.

Lower limb ischemia in diabetic patients is a result of macro- and microcirculation dysfunction. Diabetic patients undergoing limb amputation carry high mortality and morbidity rates, and decision making concerning the level of amputation is critical. Aim of this study is to evaluate a novel microdialysis technique to monitor tissue microcirculation preoperatively and predict the success of limb amputation in such patients. Overall, 165 patients with type 2 diabetes mellitus undergoing lower limb amputation were enrolled. A microdialysis catheter was placed preoperatively at the level of the intended flap for the stump reconstruction, and the levels of glucose, glycerol, lactate and pyruvate were measured for 24 consecutive hours. Patients were then amputated and monitored for 30 days regarding the outcome of amputation. Failure of amputation was defined as delayed healing or stump ischemia. Patients were divided into two groups based on the success of amputation. There was no difference between the two groups regarding gender, ASA score, body mass index, comorbidities, diagnostic modality used, level of amputation, as well as glucose, glycerol, and pyruvate levels. However, local concentrations of lactate were significantly different between the two groups and lactate/pyruvate (L/P) ratio was independently associated with failed amputation (threshold defined at 25.35). Elevated preoperative tissue L/P ratio is independently associated with worse outcomes in diabetic patients undergoing limb amputation. Therefore, preoperative tissue L/P ratio could be used as a predicting tool for limb amputation's outcome, although more clinical data are needed to provide safer conclusions.

The impact of laparoscopic sleeve gastrectomy on weight loss and obesity-associated comorbidities: the results of 3 years of follow-up.

BACKGROUND: Laparoscopic sleeve gastrectomy is one of the most recent advances in the surgical treatment of morbid obesity. Extended follow-up studies of large cohorts are needed to establish the usefulness of the operation. The objectives of this study are to delineate the role of sleeve gastrectomy in weight loss and in comorbidities among obese patients. METHODS: Patients who underwent laparoscopic sleeve gastrectomy in a single bariatric center were followed up for a 3-year period. Weight loss and status of several comorbidities were assessed at the 1st, 3rd, 6th, 12th, 18th, 24(th), and 36th postoperative month. RESULTS: Overall, after 3 years of follow-up of 88 patients, the mean body mass index (BMI) of the patients was 29.8 kg/m(2) (SD ±6.1), the % total weight loss was 38.1% (SD ±12.9), the % excess weight loss was 69.5% (SD ±17.5), and the % estimated BMI loss was 81.4% (SD ±22.3). These parameters changed significantly over the first year of follow-up (p < 0.001) and subsequently stabilized. The percentages of patients with hypertension (33.3%), hyperlipidemia (26.4%), diabetes mellitus (20.7%), obstructive sleep apnea (20.2%), and gastroesophageal reflux disease (GERD-27%) were significantly reduced (10.5, 9.2, 1.1, 1.1, and 9.2% respectively at 36 months postoperation), while 10 new cases of GERD appeared postoperatively. However, only three of the new GERD cases required medication, and only one of them experienced symptoms that persisted after the 3-year period. CONCLUSION: Three years of close follow-up of patients who had undergone laparoscopic sleeve gastrectomy demonstrated satisfactory weight loss results. Promising results were also obtained regarding various comorbidities of obese patients. Longer follow-up studies for more patients are needed to delineate the exact role of sleeve gastrectomy on postoperative outcomes.

Preoperative Cardiac Assessment before Carotid Surgery: Should Perhaps Things Change?

Carotid endarterectomy has been associated with perioperative symptomatic or asymptomatic myocardial ischemia and cardiac mortality although it has been classified as a procedure of intermediate cardiac risk. Recent data indicate that the Cardiac Risk Index score for preoperative assessment by the latest guidelines is not suitable for vascular surgery procedures in general and carotid procedures in particular. This review aims to present and analyze all these results, concluding that current recommendations for this specific procedure should perhaps be reevaluated.

Metastatic pheochromocytoma and paraganglioma.

BACKGROUND: Metastatic pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumours with a strong genetic background. DESIGN: We searched the PubMed database through February 2015 to identify studies characterizing metastatic PCs/PGLs as well as currently established and evolving therapies. RESULTS: Large size tumours (> 5 cm), PASS score > 6 and Ki-67 labelling index > 3% are the most robust indices of metastatic PCs/PGLs albeit with great variability. Germline succinate dehydrogenase complex, subunit B (SDHB) mutation constitutes the main reliable molecular predictor of malignancy. Plasma and urinary methoxytyramine are the biochemical markers characterizing metastatic PCs/PGLs along with evolving molecular markers such as miRNAs and SNAIL. Conventional imaging is used for tumour localization, whereas (18)F-FDG-PET for staging of metastatic PCs/PGLs especially those related to SDHB gene mutations. In addition, (68)Ga-DOTATATE PET/CT is emerging as a highly sensitive alternative. Surgery remains the gold standard treatment in reducing tumour bulk and/or controlling the clinical syndrome. Treatment with (131)I-MIBG or radiolabelled somatostatin analogues is considered for unresectable disease. Conventional chemotherapy is reserved for more advanced and refractory to other therapies disease although new schemes are currently evolving. Recent genetic studies have highlighted a number of pathways involved in PCs/PGLs pathogenesis directing towards the use of targeted therapies which have still to be validated in clinical practice. CONCLUSIONS: Metastatic PCs/PGLs remain an orphan disease that is only curable by surgery. However, advances in genomic analyses have improved the pathogenesis of these tumours and may lead to effective and more personalized treatments in the near future.

Predictive role of stress echocardiography before carotid endarterectomy in patients with coronary artery disease.

OBJECTIVES: Our aim was to examine the predictive value of preoperative stress echocardiography regarding early myocardial ischemia and late cardiac events after carotid endarterectomy (CEA). METHODS: Patients with coronary artery disease undergoing CEA were prospectively included in this study. All patients (n = 162) were classified into low, medium, and high cardiac risk group, according to preoperative stress echocardiography. Classification was based on the criteria of the American Society of Echocardiography. For all patients, cTnI was measured before surgery and on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Cardiac damage was defined as either myocardial ischemia or infarction. RESULTS: No deaths, strokes, or symptomatic coronary events were observed during the early postoperative period. There were 112 low cardiac risk patients, 42 medium-risk patients, and 8 high-risk patients, according to stress echocardiography findings. Overall, there were 22 patients (14%) that increased their cTnI values postoperatively (12 of low cardiac risk and 10 of medium cardiac risk), and all of them were asymptomatic. None of the high-risk patients showed any troponin increase. Late cardiac events were associated with cTnI increase, although no high-risk patients showed any late event. CONCLUSIONS: Preoperative stress echocardiography does not seem to independently recognize patients in high risk for asymptomatic cardiac damage after CEA. Postoperative troponin elevation seems to be more predictive for late adverse cardiac events than preoperative stress echocardiography.

Cardiac troponin I after carotid endarterectomy in different cardiac risk patients.

BACKGROUND: We compared postoperative cardiac damage, defined as cardiac troponin I (cTnI) elevation, in low, medium, and high cardiac risk patients, after carotid endarterectomy (CEA). METHODS: The Vascular Study Group of New England Cardiac Risk Index (VSG-CRI) criteria for stratifying patients considered for vascular surgery into low, medium, and high cardiac risk groups were used prospectively. For all patients (n = 324), cTnI value assessments were made before surgery and on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from .05 to .5 ng/mL were classified as myocardial ischemia; values more than .5 ng/mL were classified as myocardial infarction. Cardiac damage was defined as either myocardial ischemia or infarction. RESULTS: Mortality was .003%, stroke rate was null, and symptomatic myocardial infarction was null as well. Low-risk patients (16 of 140) and medium-risk patients (28 of 160) increased their troponin levels on days 1 and 3 postoperatively. However, none of the high-risk patients (n = 24) showed any postoperative cardiac damage. Low and medium cardiac risk patients showed higher troponin values on each separate day, in comparison with high cardiac risk patients. CONCLUSIONS: CEA is followed by a high incidence of asymptomatic cTnI increase that is associated with late cardiac events. However, high cardiac risk patients as defined by the VSG-CRI criteria do not seem to suffer higher cardiac damage after CEA compared with low and medium cardiac risk patients.

Tumor heterogeneity revealed by KRAS, BRAF, and PIK3CA pyrosequencing: KRAS and PIK3CA intratumor mutation profile differences and their therapeutic implications.

Current clinical problems in colorectal cancer (CRC) diagnostics and therapeutics include the disease complexity, tumor heterogeneity, and resistance to targeted therapeutics. In the present study, we examined 171 CRC adenocarcinomas from Greek patients undergoing surgery for CRC to determine the frequency of KRAS, BRAF, and PIK3CA point mutations from different areas of tumors in heterogeneous specimens. Ninety two out of 171 (53.8%) patients were found to bear a KRAS mutation in codons 12/13. Of the 126 mutations found, 57.9% (73/126) were c.38G>A mutations (p.G13D) and 22.2% (28/126) were c.35G>T (p.G12V). Remarkably, RAS mutations in both codons 12 and 13 were recorded in the same tumor by pyrosequencing. Moreover, differences in KRAS mutations between tumor center and periphery revealed tumor heterogeneity in 50.7% of the specimens. BRAF c.1799T>A (V600E) mutations were moderately detected in 4/171 (2.3%) specimens, whereas most PIK3CA mutations were revealed by pyrosequencing 6/171 (3.5%). Remarkable tumor heterogeneity is revealed, where double mutations of KRAS in the same tumor and different KRAS mutation status between tumor core and margin are detected with high frequency. It is expected that these findings will have a major impact in cancer diagnosis and personalized therapies.

Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.

Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.

The effect of laparoscopic sleeve gastrectomy on the antireflux mechanism: can it be minimized?

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a promising procedure for the treatment of morbid obesity. The stomach is usually transected near the angle of His; hence, the lower esophageal sphincter (LES) may be affected with consequences on postoperative gastroesophageal reflux disease (GERD). The purpose of this study was to examine the effect of LSG on the LES and postoperative GERD. METHODS: Severely obese asymptomatic patients submitted to LSG underwent esophageal manometry and GERD evaluation preoperatively and at least 6 weeks postoperatively. Data reviewed included patient demographics, manometric measurements, GERD symptoms, and pathology. Statistical analysis was performed by SPSS software. RESULTS: Twelve male and eleven female patients participated in the study. Mean age was 38.5 ± 10.9 years, and initial body mass index was 47.9 ± 5.1 kg/m(2). At follow-up examination, mean excess body mass index loss was 32.3 ± 12.7%. The LES total and abdominal length increased significantly postoperatively, whereas the contraction amplitude in the lower esophagus decreased. There was an increase in reflux symptoms postoperatively (p < 0.009). The operating surgeon who mostly approximated the angle of His resulted in an increased abdominal LES length (p < 0.01). The presence of esophageal tissue in the specimen correlated with increased total GERD score (p < 0.05). CONCLUSIONS: LSG weakens the contraction amplitude of the lower esophagus, which may contribute to postoperative reflux deterioration. It also increases the total and the abdominal length of the LES, especially when the angle of His is mostly approximated. However, if this approximation leads to esophageal tissue excision, reflux is again aggravated. Thus, stapling too close to the angle of His should be done cautiously.

What is the role of CHCHD2 in adrenal tumourigenesis?

PURPOSE: CHCHD2 is an antiapoptotic mitochondrial protein acting through the BCL2/BAX pathway in various cancers. However, data on the regulatory role of CHCHD2 in adrenal tumourigenesis are scarce. METHODS: We studied the expression of CHCHD2, BCL2, and BAX in human adrenocortical tissues and SW13 cells. mRNA and protein levels were analyzed through qPCR and immunoblotting, respectively, in 16 benign adrenocortical neoplasms (BANs), along with their adjacent normal adrenal tissues (controls), and 10 adrenocortical carcinomas (ACCs). BCL2/BAX mRNA expression was also analyzed in SW13 cells after CHCHD2 silencing. MTS, flow cytometry and scratch assays were performed to assess cell viability, apoptosis, and invasion, respectively. RESULTS: BCL2 and CHCHCD2 mRNA and protein expression was increased in BANs compared to normal adrenal tissues whereas BAX was decreased. BAX and CHCHD2 mRNA and protein levels were significantly downregulated and upregulated, respectively, in ACCs compared with either BANs or controls. Expression of the studied genes was not different among cortisol-secreting and nonfunctional ACAs. No significant association was found between genes' expression and other established prognostic markers of ACCs patients. In vitro analysis showed that CHCHD2 silencing resulted in reduced cell viability and invasion as well as increased SW13 cells apoptosis. CONCLUSIONS: CHCHD2 expression seems to be implicated in adrenal tumourigenesis and its absence resulted to increased apoptosis in vitro. However, the exact mechanism of action and particularly its association with the BAX/BCL2 pathway needs to be further studied and evaluate whether it could be a protentional therapeutic target.

Review of the molecular profile and modern prognostic markers for gastric lymphoma: how do they affect clinical practice?

Primary gastric lymphoma is a rare cancer of the stomach with an indeterminate prognosis. Recently, a series of molecular prognostic markers has been introduced to better describe this clinical entity. This review describes the clinical importance of several oncogenes, apoptotic genes and chromosomal mutations in the initiation and progress of primary non-Hodgkin gastric lymphoma and their effect on patient survival. We also outline the prognostic clinical importance of certain cellular adhesion molecules, such as ICAM and PECAM-1, in patients with gastric lymphoma, and we analyze the correlation of these molecules with apoptosis, angiogenesis, tumour growth and metastatic potential. We also focus on the host-immune response and the impact of Helicobacter pylori infection on gastric lymphoma development and progression. Finally, we explore the therapeutic methods currently available for gastric lymphoma, comparing the traditional invasive approach with more recent conservative options, and we stress the importance of the application of novel molecular markers in clinical practice.

Laparoscopic resection of an adrenal schwannoma.

BACKGROUND AND OBJECTIVES: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. METHODS: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. RESULTS: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5 3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. CONCLUSION: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice.

miRNAs expression pattern and machine learning models elucidate risk for gastric GIST.

BACKGROUND: Gatrointestinal stromal tumors (GISTs) are the main mesenchymal tumors found in the gastrointestinal system. GISTs clinical phenotypes differ significantly and their molecular basis is not yet completely known. microRNAs (miRNAs) have been involved in carcinogenesis pathways by regulating gene expression at post-transcriptional level. OBJECTIVE: The aim of the present study was to elucidate the expression profiles of miRNAs relevant to gastric GIST carcinogenesis, and to identify miRNA signatures that can discriminate the GIST from normal cases. METHODS: miRNA expression was tested by miScript™miRNA PCR Array Human Cancer PathwayFinder kit and then we used machine learning in order to find a miRNA profile that can predict the risk for GIST development. RESULTS: A number of miRNAs were found to be differentially expressed in GIST cases compared to healthy controls. Among them the hsa-miR-218-5p was found to be the best predictor for GIST development in our cohort. Additionally, hsa-miR-146a-5p, hsa-miR-222-3p, and hsa-miR-126-3p exhibit significantly lower expression in GIST cases compared to controls and were among the top predictors in all our predictive models. CONCLUSIONS: A machine learning classification approach may be accurate in determining the risk for GIST development in patients. Our findings indicate that a small number of miRNAs, with hsa-miR218-5p as a focus, may strongly affect the prognosis of GISTs.

Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.

As clinical efforts towards breast-conserving therapy and prolonging survival of those with metastatic breast cancer increase, innovative approaches with the use of biologics are on the rise. Two areas of current focus are cancer immunotherapy and autophagy, both of which have been well-studied independently but have recently been shown to have intertwining roles in cancer. An increased understanding of their interactions could provide new insights that result in novel diagnostic, prognostic, and therapeutic strategies. In this breast cancer-focused review, we explore the interactions between autophagy and two clinically relevant immune checkpoint pathways; the programmed cell death-1 receptor with its ligand (PD-L1)/PD-1 and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)/CD80 and CD86 (B7-1 and B7-2). Furthermore, we discuss emerging preclinical and clinical data supporting targeting both immunotherapy and autophagy pathway manipulation as a promising approach in the treatment of breast cancer.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension.

BACKGROUND: Previous studies based on standard endocrine testing have generally shown a low prevalence of primary aldosteronism, a form of autonomous aldosterone secretion (AAS), in hypertensive individuals. The purpose of this case-control study was to evaluate whether use of appropriately defined controls and combined testing reveal previously undetected AAS in hypertensives. MATERIALS AND METHODS: We investigated aldosterone secretion in 180 hypertensives with (n = 44) and without (n = 136) adrenal adenomas on computerized tomography (CT) and 72 matched nonhypertensive individuals with normal adrenal CT. Serum aldosterone and active renin were measured, and the aldosterone/active renin ratio was calculated before and after a modified fludrocortisone-suppression test (FST). In the latter, to eliminate any stimulatory effect of endogenous stress-induced adrenocorticotrophin hormone on aldosterone secretion, we administered 1 mg of dexamethasone on the last day of the classical FST fludrocortisone/dexamethasone suppression test (FDST). RESULTS: Using the 97·5 percentiles of serum aldosterone (74 pM L(-1)) and the aldosterone/renin ratio (32 pM L(-1) mU(-1) L(-1)) values obtained from the controls following the FDST, normal cut-off values indicative of adequate aldosterone suppression were established. Using the combination of these cut-offs, the estimated prevalence of AAS in patients with hypertension was 31%. Multiple linear regression analysis revealed a significant correlation between systolic and/or diastolic arterial blood pressure and the aldosterone value (P < 0·0001 and P < 0·01, respectively) and/or the aldosterone/renin ratio (P < 0·0001 and P < 0·01, respectively), which were obtained following the FDST. CONCLUSIONS: By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.