The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome.

PURPOSE: Nowadays, the standard therapy for patients with short bowel syndrome is parenteral nutrition (PN). Various growth factors have been tested to achieve weaning from prolonged PN administration. We evaluated the effect of hepatocyte growth factor (HGF) on structural intestinal adaptation and cell proliferation in a rat model of SBS. METHODS: Thirty Sprague-Dawley rats were divided into three groups; group A rats (sham) underwent bowel transection, group B rats underwent a 75% bowel resection, and group C rats underwent the same procedure but were treated postoperatively with HGF. Histopathologic parameters of intestinal adaptation were determined, while microarray and rt-PCR analyses of ileal RNA were also performed. RESULTS: Treatment with HGF resulted in significant increase in body weight, while the jejunal and ileal villus height and crypt depth were increased in HGF rats (36%, p < 0.05 and 27%, p < 0.05 respectively). Enterocyte proliferation was also significantly increased in HGF rats (21% p < 0.05). Microarray and quantitative rt-PCR analyses showed that the genes hgfac, rac 1, cdc42, and akt 1 were more than twofold up-regulated after HGF treatment. CONCLUSION: HGF emerges as a growth factor that enhances intestinal adaptation. The future use of HGF may potentially reduce the requirement for PN in SBS patients.

The impact of preoperative sarcopenia on postoperative complications following esophagectomy for esophageal neoplasia: a systematic review and meta-analysis.

Esophageal cancer is characterized by profound changes in body composition due to dysphagia and generalized cachexia. Sarcopenia or muscle wasting is a component of cachexia associated with poor postoperative performance status. The skeletal muscle index (SMI) calculated by computed tomography scans at the level of the third lumbar vertebra is an easily quantifiable and reproducible measure of sarcopenia. The aim of this meta-analysis is to investigate the impact of preoperative sarcopenia (low SMI) on postoperative complications after esophagectomy for neoplastic lesions. In this context, a comprehensive literature search was undertaken to identify studies reporting short-term postoperative outcomes in relation to their preoperative SMI values. Cumulative risk ratios (RR) and risk differences (RD) and their respective 95% confidence intervals (CIs) were calculated using a random-effect model. A total of 11 studies incorporating 1,979 total patients (964 patients with sarcopeniaversus 1,015 without sarcopenia) were included in the final analysis. The results demonstrated a significant increase in overall morbidity (RR 1.16, 95% CI 1.01-1.33), respiratory complications (RR 1.64, 95% CI 1.21-2.22) and anastomotic leaks (RR 1.39, 95% CI 1.10-1.76) in patients with sarcopenia. No statistically significant difference was noted in overall mortality (RD 0, 95% CI -0.02-0.02) or Clavien-Dindo grade III or greater complications (RR 1.17, 95% CI 0.96-1.42). The above results demonstrate the validity of the SMI as a predictive factor for post-esophagectomy complications. Although the risk associated with sarcopenia is not prohibitive for surgery, patients with low SMI require closer vigilance during their postoperative course due to the increased propensity for respiratory and anastomotic complications.

Low expression of miR-20b-5p indicates favorable prognosis in laryngeal squamous cell carcinoma, especially in patients with non-infiltrated regional lymph nodes.

PURPOSE: Tumor recurrence and distant metastasis are very common in laryngeal squamous cell carcinoma (LSCC). In this study, we examined the potential prognostic value of microRNA-20b-5p (miR-20b-5p), a component of the tumor-related miR-106a/363 cluster. MATERIALS AND METHODS: Total RNA was purified from 105 tissue specimens resected from patients having undergone surgical treatment for primary LSCC. After in vitro polyadenylation and reverse transcription, a sensitive real-time quantitative polymerase chain reaction (qPCR) methodology was applied for the relative quantification of miR-20b-5p levels. Then, we proceeded with biostatistical analysis, seeking to assess the prognostic value of miR-20b-5p expression in LSCC. RESULTS: miR-20b-5p positivity constitutes a predictor of inferior DFS and OS in LSCC (P < 0.001 and P = 0.002, respectively). The significant prognostic value of miR-20b-5p expression status seems to be independent of tumor size, histological grade, and TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis showed also that miR-20b-5p expression status can stratify LSCC patients with non-infiltrated regional lymph nodes (N0) into two subgroups with distinct prognosis (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: The miR-20b-5p expression status is a promising molecular tissue biomarker in LSCC, with an independent prognostic value, and thus merits further validation in larger cohorts of patients.

Idiopathic Double Perforation of the Gastrointestinal Tract.

A 73-year old woman was operated on with diffuse peritonitis and multiple abscesses throughout the mesentery which were drained. After the operation the patient could not recover. After an indicative computerized tomography the patient was re-explored. Perforation of the ileum and gastric perforation at the pylorus were found. There was no history of underline disease. The double perforation of the GI tract was surgically managed but the patient's course was fatal.

The effect of synbiotics on acute radiation-induced diarrhea and its association with mucosal inflammatory and adaptive responses in rats.

BACKGROUND: Previous clinical studies advocated that probiotics beneficially affect acute radiation-induced diarrhea. These encouraging results were attributed to the restoration of the intestinal flora; however, there is lack of evidence if and how probiotics influence the underlying pathophysiological mechanisms. AIMS: The present study was conducted to investigate the potential supporting role of a synbiotic preparation (combination of pro- and pre-biotics) on experimentally-induced acute radiation diarrhea from the perspective of mucosal inflammation and histological injury. METHODS: Ninety adult Wistar rats were randomly assigned into six groups. Group A (non-irradiated), group B (non-irradiated/synbiotic supplemented), group C (irradiated), and group D (irradiated/synbiotic supplemented) were followed up to a week after the beginning of the experiment. Group E (irradiated) and group F (irradiated/synbiotic supplemented) were followed up for four days. On the last day of the experiments tissues were harvested for structural and molecular assessments. RESULTS: Synbiotic administration could not avert the occurrence of diarrhea, but significantly attenuated its severity. This effect was associated with the significant downregulation of neutrophil accumulation and lipid peroxidation during the acute phase. During the subacute phase, synbiotic treatment significantly improved both the histological profile and radiation mucositis. These mechanisms significantly contributed to the rehabilitation of the intestinal absorptive function as further indicated from the significantly reduced weight loss. CONCLUSIONS: Given the optimization of the intestinal flora exerted by synbiotics, the resolution of diarrhea relies on the suppression of the "reactive" and the augmentation of "regenerative" components of acute radiation-induced intestinal response.

Gallstone Ileus in Octogenarians: Is Cholecystectomy Really Needed?

Gallstone ileus is an uncommon complication of cholelithiasis and occurs when a gallstone migrates through a cholecystoenteric fistula and impacts within the gastrointestinal tract. Surgical intervention remains the treatment of choice, which consists of a full-thickness incision of the visceral wall and removal of the impacted gallstone. In this paper we present the treatment approach of 6 cases of gallstone ileus in octogenarians. In our cohort, intestinal obstruction was resolved through an enterotomy or gastrotomy and lithotomy/stone extraction in every patient. No cholecystectomies were undertaken. Despite the fact that gallstone ileus is diagnosed in small percent of patients suffering from gallstone disease, it accounts for a large proportion of intestine obstruction in patients older than 65 years old. Since accurate diagnosis and timely intervention are vital, providers should be familiar with the diagnostic approach and the treatment of this clinical entity.

Antioxidant properties of probiotics and their protective effects in the pathogenesis of radiation-induced enteritis and colitis.

Radiation therapy has become one of the most important treatment modalities for human malignancy, but certain immediate and delayed side-effects on the normal surrounding tissues limit the amount of effective radiation that can be administered. After exposure of the abdominal region to ionizing radiation, nearly all patients experience transient symptoms of irradiation of the bowel. Acute-phase symptoms may persist for a short time, yet long-term complications can represent significant clinical conditions with high morbidity. Data from both experimental studies and clinical trials suggest the potential benefit for probiotics in radiation-induced enteritis and colitis. On the other hand, it is well evidenced that both useful and harmful effects of therapeutic applications of ionizing radiation upon living systems are ascribed to free-radical production. Therefore, the hypothesis that probiotics reinforce antioxidant defense systems of normal mucosal cells exposed to ionizing radiation may explain to an extent their beneficial action. The aim of this review is threefold: First, to make a short brief into the natural history of radiation injury to the intestinal tract. Second, to describe the primary interaction of ionizing radiation at the cellular level and demonstrate the participation of free radicals in the mechanisms of injury and, third, to try a more profound investigation into the antioxidant abilities of probiotics and prebiotics based on the available experimental and clinical data.

Potential benefits of pro- and prebiotics on intestinal mucosal immunity and intestinal barrier in short bowel syndrome.

The mechanism of impaired gut barrier function in patients with short bowel syndrome (SBS) is poorly understood and includes decreased intestinal motility leading to bacterial overgrowth, a reduction in gut-associated lymphoid tissue following the loss of intestinal length, inhibition of mucosal immunity of the small intestine by intravenous total parental nutrition, and changes in intestinal permeability to macromolecules. Novel therapeutic strategies (i.e. nutritive and surgical) have been introduced in order to prevent the establishment or improve the outcome of this prevalent disease. Pre- and probiotics as a nutritive supplement are already known to be very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanisms, such as the production of SCFA which influence epithelial cell metabolism, turnover and apoptosis. Probiotics have been recommended for patients suffering from SBS in order to decrease bacterial overgrowth and prevent bacterial translocation, two major mechanisms in the pathogenesis of SBS. The present review discusses the research available in the international literature, clinical and experimental, regarding probiotic supplementation for this complicated group of patients based on the clinical spectrum and pathophysiological aspects of the syndrome. The clinical data that were collected for the purposes of the present review suggest that it is difficult to correctly characterise probiotics as a preventive or therapeutic measure. It is very challenging after all to examine the relationship of the bacterial flora, the intestinal barrier and the probiotics as, according to the latest knowledge, demonstrate an interesting interaction.

Gastrointestinal stromal tumors (GISTs): an updated experience.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors of the digestive tract characterized by c-KIT mutations. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors. METHODS: The stomach is the most commonly involved site for these tumors in the digestive tract. Computed tomography and endoscopy can usually establish the diagnosis. The study of certain specific immunohistochemical markers may contribute to better characterization of these tumors. RESULTS: Surgical resection of GISTs has been the most effective therapy. In addition, targeted therapy with tyrosine kinase inhibitors may reduce the development of recurrence or decrease the disease progression in patients with metastatic disease. CONCLUSIONS: The introduction of tyrosine kinase inhibitors has resulted in significant improvement in the overall prognosis of these patients. Furthermore, preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs.

Radial Basis Function Artificial Neural Network for the Investigation of Thyroid Cytological Lesions.

OBJECTIVE: This study investigates the potential of an artificial intelligence (AI) methodology, the radial basis function (RBF) artificial neural network (ANN), in the evaluation of thyroid lesions. Study Design. The study was performed on 447 patients who had both cytological and histological evaluation in agreement. Cytological specimens were prepared using liquid-based cytology, and the histological result was based on subsequent surgical samples. Each specimen was digitized; on these images, nuclear morphology features were measured by the use of an image analysis system. The extracted measurements (41,324 nuclei) were separated into two sets: the training set that was used to create the RBF ANN and the test set that was used to evaluate the RBF performance. The system aimed to predict the histological status as benign or malignant. RESULTS: The RBF ANN obtained in the training set has sensitivity 82.5%, specificity 94.6%, and overall accuracy 90.3%, while in the test set, these indices were 81.4%, 90.0%, and 86.9%, respectively. Algorithm was used to classify patients on the basis of the RBF ANN, the overall sensitivity was 95.0%, the specificity was 95.5%, and no statistically significant difference was observed. CONCLUSION: AI techniques and especially ANNs, only in the recent years, have been studied extensively. The proposed approach is promising to avoid misdiagnoses and assists the everyday practice of the cytopathology. The major drawback in this approach is the automation of a procedure to accurately detect and measure cell nuclei from the digitized images.

Diffuse anorectal melanoma; review of the current diagnostic and treatment aspects based on a case report.

Primary anorectal melanoma is a rare and aggressive disease. Patients commonly complain for changes in bowel habits and rectal bleeding, and proctoscopically they mostly appear as non pigmented or lightly pigmented polypoid lesions. Such a lesion should always raise a high index of suspicion in any gastroenterologist or surgeon to prompt surgery, since early radical excision is the only treatment option.Herein, we report a case of a 57-year-old man with a diffuse anal canal melanoma and give reference to the current diagnostic and treatment options.

Metastatic squamous cell carcinoma to the pancreas: Report of an extremely rare case.

Secondary pancreatic lesions are very uncommon. Resection of these metastatic lesions with a curative intent has been reported in selected patients; however, the survival benefit from these procedures has yet to be clearly determined. A 78-year-old male patient presented to our department with obstructive jaundice. Three years prior to presentation the patient had undergone right pneumonectomy, due to stage IIA, low-grade squamous cell lung carcinoma. After resection, the patient received adjuvant chemotherapy, with no evidence of local or systemic recurrence over the following 3 years. Abdominal computer tomography on admission revealed a 3-cm lesion located at the head of the pancreas, causing biliary obstruction. Endoscopic ultrasound biopsy revealed malignant cells, suspicious for squamous cell carcinoma. Due to the limited extent of the metastatic disease and in view of the patient's good condition, surgical resection was proposed and the patient successfully underwent pancreaticoduodenectomy. Histological examination of the resected specimen confirmed a squamous cell carcinoma, with an immunochemical profile similar to that of the primary lung tumor. Therefore, pancreatic resection with curative intent may be feasible in selected patients with secondary metastatic tumors. However, further studies are required in order to determine the benefit of these major procedures in terms of survival outcomes.

Ten-year survival outcomes of patients with potentially resectable gastric cancer: impact of clinicopathologic and treatment-related risk factors.

BACKGROUND: Despite therapeutic advancements, gastric cancer (GC) remains a leading cause of death worldwide. METHODS: This retrospective cohort study statistically analyzed the clinicopathologic characteristics, treatments and outcomes of patients with potentially resectable GC managed at our institution between 2006 and 2010. The STROBE checklist was applied. RESULTS: Preoperative assessment of 164 GC patients (male: female ratio 1.87, median age 65 years) assigned 132 (80.5%) to total (56; 42.4%) or subtotal (76; 57.6%) gastrectomy. Resection margins were microscopically tumor-free (R0) in 100 (75.8%), microscopically infiltrated (R1) in 25 (18.9%) and macroscopically infiltrated (R2) in 7 (5.3%) patients. Nodal plane dissection was D0 in 34 (25.8%), D1 in 62 (47.0%) and D2 in 36 (27.3%) patients. Early GC was diagnosed in 19 patients (14.4%). Fluorouracil-based chemotherapy was administered in 69.7% and chemoradiation in 18.2% of patients. The 5- and 10-year survival rates of patients with R0 resection were 74% and 65.4%, respectively. The 2-year survival rates for R1 and R2 resection were 28.9% and 0% respectively. The 5- and 10-year survival rates according to nodal plane dissection were 55.6% and 41.4% for D2, and 53.2% and 49.7% for D1, respectively. On multivariate analysis, T4, N3 and R1/R2 remained independent negative prognostic factors for overall survival. Microscopic or macroscopic infiltration of surgical margins was the worst adverse prognostic factor for survival. CONCLUSION: These results are equivalent to those from centers of excellence and indicate the urgent need for improvements in the field, particularly in the development of predictive models to guide personalized therapy.

Small bowel perforation with multiple intestinal metastases from lung carcinoma: A case report.

The present report describes the case of an 81-year-old woman who underwent an emergency explorative laparotomy due to small bowel perforation. Diffuse feculent peritonitis due to perforation of the jejunum was identified. In addition, six distinct tumors of the jejunum in close proximity to the perforation site, as well as two more lesions caudally at the ileum, were identified. A separate stenotic tumor was identified at the sigmoid colon, causing moderate dilatation of the whole intestine. An enterectomy, including the perforation site and the proximal six tumors, was performed, followed by limited enterectomies for the distal two tumors and side-to-side anastomoses of the small intestine. All resected tumors were identified at histology as metastatic from lung carcinoma. Postoperatively, the patient remained in a severe septic condition and succumbed the following day. Metastatic lesions from lung carcinoma in the small bowel wall are a rare finding predisposing to bowel perforation. When an acute condition coexists with multiple intestinal metastases, the mortality rate is high despite prompt surgical intervention.

Laparoscopic ventral hernia repair: pros and cons compared with open hernia repair.

BACKGROUND: The purpose of this study was to analyse the surgical techniques, perioperative complications, and recurrence rate of laparoscopic ventral hernia repair (LVHR), in comparison with the open ventral hernia repair (OVHR), based on the international literature. METHODS: A Medline search of the English literature was performed using the term "laparoscopic ventral hernia repair." Further articles were found by cross-referencing the references of each main article. RESULTS: Current literature on the topic suggests that LVHR is a safe alternative to the open method with the main advantages being minimal postoperative pain, a shorter convalescence period, and better cosmetic results. Main complications after the laparoscopic approach, such as incidental enterotomy, protracted pain, postoperative seroma, or mesh infection occur at an acceptable rate. Furthermore, most articles favor LVHR versus OVHR in terms of recurrence rate. CONCLUSIONS: Although further randomized studies are needed to draw safe conclusions in terms of complications and recurrence, LVHR is fast becoming the standard approach in the repair of abdominal wall hernias.

A huge asymptomatic pheochromocytoma.

Due to their evolution in the retroperitoneal space, pheochromocytomas may grow significantly in size and remain asymptomatic for a long period of time. Normal values of urine catecholamine levels must not preclude the diagnosis of these endocrine lesions.

De Garengeot's Hernia: Report of a Rare Surgical Emergency and Review of the Literature.

This is a report of a case who was admitted and operated on for a strangulated femoral hernia. The hernia sac contained a gangrenous appendix, which was excised and the hernia was repaired with sutures without complication. De Garengeot's hernia, although very rare, should be included in the differential diagnosis of cases with strangulated hernia and should receive the optimal treatment.

A short review of primary aldosteronism in a question and answer fashion.

OBJECTIVES: The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. METHODS: We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery. We also did cross-referencing search with the above terms. We had divided our study into five sections: Introduction, Diagnosis, Genetics, Treatment, and Conclusions. We present our results in a question and answer fashion in order to make reading more interesting. RESULTS: PA should be searched in all high-risk populations. The gold standard for diagnosis PA is the plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we proceed with one of the four confirmatory tests. If positive, then we proceed with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the lesion is unilateral, after proper preoperative preparation, we proceed, in adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit for surgery, we treat them with mineralocorticoid receptor antagonists, usually spironolactone. CONCLUSIONS: Primary aldosteronism is the most common and a treatable case of secondary hypertension. Only patients with unilateral adrenal diseases are eligible for surgery, while patients with bilateral and non-surgically correctable PA are usually treated by mineralocorticoid receptor antagonist (MRA). Thus, the distinction between unilateral and bilateral aldosterone hypersecretion is crucial.

Reversal of Novel Anticoagulants in Emergent Surgery and Trauma: A Comprehensive Review and Proposed Management Algorithm.

Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC's anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

Laparoscopic cholecystectomy after open cholecystostomy for gallbladder empyema: a case report.

The case of a patient with gallbladder empyema initially drained through a minilaparotomy procedure under local anesthesia with a tube cholecystostomy is reported in this paper. Eight weeks later, the patient underwent an elective interval laparoscopic cholecystectomy. At laparoscopy, the gallbladder and the cholecystostomy tube were dissected free from the abdominal wall and the greater omentum, which was attached to the gallbladder. The tube was removed from the gallbladder fundus, and the operation was completed laparoscopically without any major problems.