Colon micro- and macrooesofagisation in interposed pedicled colonic right half segments for esophagus reconstruction.

Treatment of esophageal burns may require surgical transplantation (interposition) of the colon or stomach. The interposed parts change their function and morphology. To investigate the macro- and microchanges in the transplanted colonic segment we analyzed in long-term follow-up (up to 29 years) the group of 21 patients in a retrospective study who underwent surgical interposition of pedicled colonic right half segments for esophageal burns. The data were analyzed statistically with the software package Statistica 13 (StatSoft Polska, Cracow). All calculations were performed with a significant level of P = .05. We evaluated the macro- and microanatomy of the grafts using radiology, endoscopy and histology. The adaptation of the transplanted tube was excellent. The diameter of the colonic tube was normal (35-60 mm) in 60% of females and 100% of males. Typical macrooesophagisation was found in all patients, while microoesophagisation involved inflammation, which gradually resolved over a period of about 5 years to be replaced by edema without fibrosis. Only in few patients persistent reflux was present, leading to erosions or ulcerations. All symptoms subsided after conservative treatment. We concluded macrooesophagization developed gradually after surgery, and was fully developed after 15 to 20 years. Microoesophagization appeared soon after interposition, and was obvious after 5 years. No metaplasia or dysplasia were observed (except in 1 patient), and the number of goblet cell remained constant.

Effect of LDHA Inhibition on TNF-α-Induced Cell Migration in Esophageal Cancers.

Cell migration is an essential part of the complex and multistep process that is the development of cancer, a disease that is the second most common cause of death in humans. An important factor promoting the migration of cancer cells is TNF-α, a pro-inflammatory cytokine that, among its many biological functions, also plays a major role in mediating the expression of MMP9, one of the key regulators of cancer cell migration. It is also known that TNF-α is able to induce the Warburg effect in some cells by increasing glucose uptake and enhancing the expression and activity of lactate dehydrogenase subunit A (LDHA). Therefore, the aim of the present study was to investigate the interrelationship between the TNF-α-induced promigratory activity of cancer cells and their glucose metabolism status, using esophageal cancer cells as an example. By inhibiting LDHA activity with sodium oxamate (SO, also known as aminooxoacetic acid sodium salt or oxamic acid sodium salt) or siRNA-mediated gene silencing, we found using wound healing assay and gelatin zymography that LDHA downregulation impairs TNF-α-dependent tumor cell migration and significantly reduces TNF-α-induced MMP9 expression. These effects were associated with disturbances in the activation of the ERK1/2 signaling pathway, as we observed by Western blotting. We also reveal that in esophageal cancer cells, SO effectively reduces the production of lactic acid, which, as we have shown, synergizes the stimulating effect of TNF-α on MMP9 expression. In conclusion, our findings identified LDHA as a regulator of TNF-α-induced cell migration in esophageal cancer cells by the ERK1/2 signaling pathway, suggesting that LDHA inhibitors that limit the migration of cancer cells caused by the inflammatory process may be considered as an adjunct to standard therapy in esophageal cancer patients.

MMP9: A Tough Target for Targeted Therapy for Cancer.

Having the capability to proteolyze diverse structural and signaling proteins, matrix metalloproteinase 9 (MMP9), one of the best-studied secretory endopeptidases, has been identified as a crucial mediator of processes closely associated with tumorigenesis, such as the extracellular matrix reorganization, epithelial to mesenchymal transition, cell migration, new blood vessel formation, and immune response. In this review, we present the current state of knowledge on MMP9 and its role in cancer growth in the context of cell adhesion/migration, cancer-related inflammation, and tumor microenvironment formation. We also summarize recent achievements in the development of selective MMP9 inhibitors and the limitations of using them as anticancer drugs.

New classifications of axillary lymph nodes and their anatomical-clinical correlations in breast surgery.

BACKGROUND: In the last decade, two research groups, the French group by Clough et al. (Br J Surg. 97:1659-65, 2010) and the Chinese one by Li et al. (ISRN Oncol 2013:279013, 2013), proposed two types of classification of axillary lymph nodes in breast cancer, identifying novel anatomic landmarks for dividing the axillary space in lymph node dissection. MAIN BODY: Knowledge of the exact location of the sentinel node helps to focus the surgical dissection and to reduce the morbidity of sentinel lymph node biopsy procedures, in particular the risk of arm lymphedema, without compromising sensitivity. CONCLUSION: In this article, we aimed at focusing on the clinical impact that the most recent classifications of axillary lymph nodes have obtained in literature, highlighting the importance of defining new demarcations to preserve the axillary lymph nodes as much as possible in breast surgery.

The Effect of Neddylation Inhibition on Inflammation-Induced MMP9 Gene Expression in Esophageal Squamous Cell Carcinoma.

Inhibition of the protein neddylation process by the small-molecule inhibitor MLN4924 has been recently indicated as a promising direction for cancer treatment. However, the knowledge of all biological consequences of MLN4924 for cancer cells is still incomplete. Here, we report that MLN4924 inhibits tumor necrosis factor-alpha (TNF-α)-induced matrix metalloproteinase 9 (MMP9)-driven cell migration. Using real-time polymerase chain reaction (PCR) and gelatin zymography, we found that MLN4924 inhibited expression and activity of MMP9 at the messenger RNA (mRNA) and protein levels in both resting cells and cells stimulated with TNF-α, and this inhibition was closely related to impaired cell migration. We also revealed that MLN4924, similar to TNF-α, induced phosphorylation of inhibitor of nuclear factor kappa B-alpha (IκB-α). However, contrary to TNF-α, MLN4924 did not induce IκB-α degradation in treated cells. In coimmunoprecipitation experiments, nuclear IκB-α which formed complexes with nuclear factor kappa B p65 subunit (NFκB/p65) was found to be highly phosphorylated at Ser32 in the cells treated with MLN4924, but not in the cells treated with TNF-α alone. Moreover, in the presence of MLN4924, nuclear NFκB/p65 complexes were found to be enriched in c-Jun and cyclin dependent kinase inhibitor 1 A (CDKN1A/p21) proteins. In these cells, NFκB/p65 was unable to bind to the MMP9 gene promoter, which was confirmed by the chromatin immunoprecipitation (ChIP) assay. Taken together, our findings identified MLN4924 as a suppressor of TNF-α-induced MMP9-driven cell migration in esophageal squamous cell carcinoma (ESCC), likely acting by affecting the nuclear ubiquitin-proteasome system that governs NFκB/p65 complex formation and its DNA binding activity in regard to the MMP9 promoter, suggesting that inhibition of neddylation might be a new therapeutic strategy to prevent invasion/metastasis in ESCC patients.

Invadopodia: clearing the way for cancer cell invasion.

The invasive nature of many cancer cells involves the formation of F-actin-based, lipid-raft-enriched membrane protrusions known as invadopodia or, more broadly, invadosomes. Invadopodia are specialized adhesive structures arising from ventral cell surface within cell-extracellular matrix (ECM) contacts and concentrate high proteolytic activities that allow cells to overcome the dense scaffold of local microenvironment, comprising a natural barrier to cell spreading. This degradative activity distinguishes invadopodia from other adhesive structures like focal adhesions, lamellipodia or filopodia, and is believed to drive cancer progression.

The usefulness of lactate dehydrogenase measurements in current oncological practice.

One of the hallmarks of cancer cells is increased energy requirements associated with the higher rate of cellular proliferative activity. Metabolic changes in rapidly dividing cancer cells are closely associated with increased uptake of glucose and abnormal activity of lactate dehydrogenase (LDH), which regulates the processing of glucose to lactic acid. As serum LDH levels were found to be commonly increased in cancer patients and correlated with poor clinical outcome and resistance to therapy, the determination of LDH has become a standard supportive tool in diagnosing cancers or monitoring the effects of cancer treatment. The aim of this review is to summarize the current knowledge about methods and the practical utility for measuring both the total LDH and LDH isoenzymatic activities in the diagnosis, prognosis and prediction of cancer diseases.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications.

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient's hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteremia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications.

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient's hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteremia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

Modified Paul-Mikulicz jejunostomy in frail geriatric patients undergoing emergency small bowel resection.

BACKGROUND: Proximal or extended bowel resections are sometimes necessary during emergency surgery of the small bowel and call for creating a high small bowel stomy as a part of damage control surgery. Secondary restoration of intestinal continuity in the frail geriatric patient, further weakened by subsequent severe malabsorption may be prohibitive. METHODS: Six patients underwent emergency small bowel resection for proximal jejunal disease (83.3% high-grade adhesive SBO and 16.7% jejunal diverticulitis complicated with perforation). With the intention to avoid end jejunostomy and the need for repeat laparotomy for bowel continuity restoration we modified the classic Paul-Mikulicz jejunostomy. RESULTS: The postoperative course was uneventful in four patients whose general condition improved considerably. At six-month follow-up, neither patients required parenteral nutrition. CONCLUSIONS: This modified stoma can have the advantage of allowing a partial passage of the enteric contents, reducing the degree of malabsorption, and rendering jejunostomy reversal easy to perform later.

Clinical signs of retroperitoneal abscess from colonic perforation: Two case reports and literature review.

RATIONALE: Retroperitoneal colonic perforation is a rare cause of retroperitoneal abscess. It presents, more frequently in frail elderly patients, with heterogeneous signs and symptoms which hamper the clinical diagnosis. Subcutaneous emphysema with pneumomediastinum and iliopsoas muscle abscess are unusual signs. Colonic retroperitoneal perforation may be consequent to diverticulitis or locally advanced colon cancer. Due to the anatomy of the retroperitoneal space and different physiopathology, diverticular perforation may present with air and pus collection; on the other hand perforated colon cancer may cause groin mass and psoas abscess. We reported 2 cases of colonic retroperitoneal perforation from diverticulitis and locally advanced colon cancer, respectively. Aim of this report is to improve differential diagnosis based on clinical signs. PATIENTS' CONCERNS: A 71-year-old man presented with pain in his left side, fatigue, fever, nausea, massive subcutaneous emphysema of the neck, and Blumberg sign in the left iliac fossa. A 67-year-old man presented with abdominal pain, sub-occlusion, left groin mass, left groin, and lower limb pain during walking, negative Blumberg sign. DIAGNOSIS: In the first patient the computerized tomography revealed pneumoperitoneum, gas in the mesosigma, pneumomediastinum, wall thickening of the descending colon, and retroperitoneal collection from diverticular perforation. In the second patient abdominal CT scan found thickening of the sigmoid colon adherent to the iliopsoas and fluid collection. INTERVENTIONS: In the first patient, a left hemicolectomy extending to the transverse colon, followed by a toilette and debridement of the retroperitoneum were performed. In the second patient, tumor of descending colon perforated in the retroperitoneum with iliopsoas abscess was treated with left hemicolectomy and a drainage of the abscess. OUTCOMES: The first patient underwent right colectomy with ileostomy in the 7 postoperative day for large bowel necrosis. He died of sepsis 2 days after. The second patient had regular postoperative and he is still alive. LESSONS: The spread of retroperitoneal abscess in complicated colonic diverticulitis is different from that in advanced colonic cancer. The former can present with a subcutaneous emphysema, the latter with a groin mass. Hence a thorough clinical examination and radiological studies are needed to diagnose these conditions.

Surgical treatment of gastrointestinal stromal tumors of the duodenum: a literature review.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumours in the digestive tract. The duodenal GIST (dGIST) is the rarest subtype, representing only 4-5% of all GIST, but up to 21% of the resected ones. The diagnostic and therapeutic management of dGIST may be difficult due to the rarity of this tumor, its anatomical location, and the clinical behavior that often mimic a variety of conditions; moreover, there is lack of consent for their treatment. This study has evaluated the scientific literature to provide consensus on the diagnosis of dGIST and to outline possible options for surgical treatment. METHODS: An extensive research has been carried out on the electronic databases MEDLINE, Scopus, EMBASE and Cochrane to identify all clinical trials that report an event or case series of dGIST. RESULTS: Eighty-six studies that met the inclusion criteria were identified with five hundred forty-nine patients with dGIST: twenty-seven patients were treated with pancreatoduodenectomy and ninety-six with only local resection (segmental/wedge resections); in four hundred twenty-six patients it is not possible identify the type of treatment performed (pancreatoduodenectomy or segmental/wedge resections). CONCLUSIONS: dGISTs are a very rare subset of GISTs. They may be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumours smaller than 2 cm have a low biological aggressiveness and can be followed annually by endoscopic ultrasound. The biggest ones should undergo radical surgical resection (R0). In dGIST there is no uniformly adopted surgical strategy because of the low incidence, lack of experience, and the complex anatomy of the duodenum. Therefore, individually tailored surgical approach is recommended. R0 resection with 1-2 cm clear margin is required. Lymph node dissection is not recommended due to the low incidence of lymphatic metastases. Tumor rupture should be avoided.

Zenker diverticulum: Experience in surgical treatment of large diverticula.

The purpose of this retrospective study is to show that transcervical diverticulectomy (TD) in treatment of Zenker diverticulum (ZD) can still be a first choice procedure in selected patients and in experienced hands its safety might be compared to the minimally invasive endoscopic diverticulostomy.The study cohort consisted of 44 patients (18 male, 26 female) operated for (ZD). All the patients underwent open diverticulectomy. The decision to choose open surgical repair depended on surgical risk, age of the patient, size of the diverticular septum (the distance between the top of the diverticulum and its bottom on barium study), and patient's preference.Mean age of patients was 64.6 ±â€Š11.9 years; range: 26 to 88 years. A total of 36.4% out of them finished 70 years. Postoperative mortality was nil. Two major complications (4.5%) requiring surgical intervention occurred: leak and hematoma.Data were analyzed by t test for independent samples using Statistica 12.5 software. P value <0.05 was considered statistically significant.Surgical treatment of patients with ZD should be individualized. Large Zenker diverticula with the septum longer than 6 cm should preferably be resected through an open approach because it is not possible to remove the septum completely during one-step endoscopic procedure and diverticulostomy creates a weak and large common cavity in the esophagus. Surgical repair is effective for all sizes of diverticula, but its most serious complications such as leakage or laryngeal nerve injury should be considered, especially in elderly patients with comorbidities. However, age alone should not be the main criterion if choosing the treatment option.

A novel regulatory function of CDKN1A/p21 in TNFα-induced matrix metalloproteinase 9-dependent migration and invasion of triple-negative breast cancer cells.

Metastasis is the leading cause of mortality in patients with highly invasive cancers and, as such, is a major problem for medicine. It has been increasingly recognized that cancer-related inflammation plays an important role in promoting invasion and the metastatic process in which cell motility and upregulation of proteolytic enzymes are crucial events. TNFα is a proinflammatory cytokine known to stimulate synthesis of MMP9, a zinc- and calcium-dependent endopeptidase contributing to the regulation of ECM remodeling and cell signaling. However, the precise molecular mechanism of TNFα-induced MMP9 gene expression in cancers is still not fully understood. This study shows that TNFα-induced cell migration and invasion involve ERK1/2-dependent up-regulation of CDKN1A/p21 expression in highly aggressive breast cancer cells and that CDKN1A/p21 plays an important regulatory role in TNFα-induced MMP9 gene expression, indicating an unknown function of CDKN1A/p21 as a regulator of proteolytic activity in cancer cells.

Laparoscopy for Trauma and the Changes in its Use From 1990 to 2016: A Current Systematic Review and Meta-Analysis.

BACKGROUND: The role of laparoscopy in the diagnosis and treatment of stable abdominal trauma patients is still a matter of serious debate and only incomplete data are available. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of the literature between January 1990 and August 2016. RESULTS: Overall, 9817 laparoscopies were performed for abdominal trauma; only 26.2% of the cases were converted to a laparotomy. The incidence of therapeutic laparotomies showed a reduction from 69% to 47.5%, whereas the incidence of therapeutic laparoscopies increased from 7.2% to 22.7%.The overall perioperative mortality rate was significantly lower in the laparoscopy group [odds ratio (M-H, random); 95% confidence interval, 0.35 (0.26-0.48)]. The same group showed shorter length of hospital stay [odds ratio (M-H, random); 95% confidence interval, -3.48 (-8.91 to 1.96)]. CONCLUSIONS: This systematic review shows a significant decrease in the use of laparoscopy in trauma patients. Most likely the widespread use of imaging techniques allows a more accurate selection of patients for diagnostic laparoscopy. Infact, a reduction in incidence of nontherapeutic laparotomies is evident in these selected patients undergoing diagnostic laparoscopy. Moreover, the literature reported an increasing trend of therapeutic laparoscopy, demonstrating that it is safe and effective. The small number and poor quality of the studies identified, the retrospective observational nature of the studies (low level of evidence), the high risk of bias, and the high heterogeneity of some outcomes make the applicability of the results of this meta-analysis unclear.

Fibroblast activating protein-α expression in squamous cell carcinoma of the esophagus in primary and irradiated tumors: the use of archival FFPE material for molecular techniques.

There are numerous reports suggesting that fibroblast activating protein-α (FAP-α) plays an important role in invasion of various tumor types. We studied the expression pattern of FAP-α in esophageal squamous cell carcinoma (ESCC) patients who had not been treated primarily and those who had received neoadjuvant radiochemotherapy. Our goal was to establish whether readily available tissue specimens fixed in formalin and stored in paraffin blocks for years might still be a source of FAP-α RNA for PCR analysis. The study included 20 patients divided into two groups, 10 patients in each group. We evaluated the expression of FAP-α by PCR techniques in fresh frozen and in paraffin-embedded tissues, and compared it to the expression in non-cancer tissues. To detect the protein expression level of FAP-α in paraffin-embedded tissues we used chromogenic immunohistochemical (IHC) staining. Data were analyzed by t-test or the nonparametric Wilcoxon matched pair test using Statistica 12.5 software. We observed an increased level of the FAP-alpha gene and protein expression in cancer tissues when compared with their corresponding normal tissues. However, statistically significant differences were found only in the group of patients untreated before surgery. RNA extracted from paraffin-embedded tissue sections had very low quality, especially in the context of degradation. FAP-α remains a highly altered participant of a complex microenvironment in esophageal squamous cell carcinoma, and its role in cell signaling requires further study. In this paper, we conclude that the use of a regular RT-PCR method for diagnostic purposes, which we have presented in an earlier paper, can be as good as qRT-PCR. Also, immunohistochemistry proved to be very useful and the only reliable method that can be used on formalin-fixed, paraffin-embedded tissues stored long term.

A systematic review of the management and outcome of ERCP related duodenal perforations using a standardized classification system.

INTRODUCTION: The incidence of duodenal perforation after ERCP ranges from 0.09% to 1.67% and mortality up to 8%. METHODS: This systematic review was registered in Prospective Register of Systematic Reviews, PROSPERO. Stapfer classification of ERCP-related duodenal perforations was used. RESULTS: The systematic search yielded 259 articles. Most frequent post-ERCP perforation was Stapfer type II (58.4%), type I second most frequent perforation (17.8%) followed by Stapfer type III in 13.2% and type IV in 10.6%. Rate of NOM was lowest in Stapfer type I perforations (13%), moderate in type III lesions (58.1%) and high in other types of perforations (84.2% in type II and 84.6% in IV). In patients underwent early surgical treatment (<24 h from ERCP) the most frequent operation was simple duodenal suture with or without omentopexy (93.7%). In patients undergoing late surgical treatment (>24 h from ERCP) interventions performed were more complex. In type I lesions post-operative mortality rate was higher in patients underwent late operation (>24 h). In type I lesions, failure of NOM occurred in 42.8% of patients. In type II failure of NOM occurred in 28.9% of patients and in type III there was failure of NOM in only 11.1%, none in type IV. Postoperative mortality after NOM failure was 75% in type I, 22.5% in type II and none died after surgical treatment for failure of NOM in type III perforations. CONCLUSIONS: This systematic review showed that in patients with Stapfer type I lesions, early surgical treatment gives better results, however the opposite seems true in Stapfer III and IV lesions.