Multiple primary malignances managed with surgical excision: a case report with next generation sequencing analysis.

BACKGROUND: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases. METHODS AND RESULTS: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers. CONCLUSIONS: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development.

Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor. CONCLUSION: This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.

Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM).

BACKGROUND: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. SUMMARY: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.

Surgery in biliary lithiasis: from the traditional "open" approach to laparoscopy and the "rendezvous" technique.

BACKGROUND: According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones (CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient's age. Compared to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic surgery, together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with gallstones. DATA SOURCES: We decided to systematically review the literature in order to identify all the current therapeutic options for CBDS. A systematic literature search was performed independently by two authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. RESULTS: The therapeutic approach nowadays varies greatly according to the availability of experience and expertise in each center, and includes open or laparoscopic common bile duct exploration, various combinations of laparoscopic cholecystectomy and ERCP and combined laparoendoscopic rendezvous. CONCLUSIONS: Although ERCP followed by laparoscopic cholecystectomy is currently preferred in the majority of hospitals worldwide, the optimal treatment for concomitant gallstones and CBDS is still under debate, and greatly varies among different centers.

Resistin-like beta reduction is associated to low survival rate and is downregulated by adjuvant therapy in colorectal cancer patients.

Colorectal Cancer (CRC) is one of the most common cancers accounting for 1.8 million new cases worldwide every year. Therefore, the identification of new potential therapeutic targets represents a continuous challenge to improve survival and quality of CRC patient's life. We performed a microarray analysis dataset consisting of colon biopsies of healthy subjects (HS) and CRC patients. These results were further confirmed in a clinical setting evaluating a series of CRC patients to assess the expression of Resistin-Like Beta (RETNLB) and to correlate it with their clinical data. Our results showed a significant reduction of RETNLB expression in CRC biopsies compared to the HS mucosa. Furthermore, such reduction was significantly associated with the TNM grade and patients' age. Furthermore, a significantly positive correlation was found within mutated subjects for KRAS, TP53, and BRAF. In particular, patients with poor prognosis at 5 years exhibited RETNLB lower levels. In-silico analysis data were confirmed by histochemical analysis in a series of CRC patients recruited by our group. The results obtained provided that RETNLB low levels are associated with an unfavorable prognosis in CRC patients and its expression is also dependent on adjuvant therapy. Further studies are warranted in order to evaluate the molecular mechanisms underlying the role of RETNLB in CRC progression.

Cytotoxic and immune-sensitizing properties of nitric oxide-modified Saquinavir in iNOS-positive human melanoma cells.

We have recently shown that covalent attachment of the NO moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity. In this study we evaluated the impact of Saq-NO on the growth of A375 human melanoma cells, as a prototype of NO-dependent cancer model. The novel compound strongly affected the in vitro and in vivo progression of A375 melanoma cell growth. The mechanism of antimelanoma action comprised dual drug activity-induction of apoptotic cell death and acquisition of melanoma cell responsiveness to TRAIL. Saq-NO-triggered apoptosis was dependent on transient AKT up-regulation and reduced pERK and iNOS expression that were observed within the first 12 h of exposure to the drug. Thereafter, however, Saq-NO up-regulated both iNOS transcription and NO endogenous synthesis and sensitized A375 cells to TRAIL. Furthermore, reduced YY1 expression was observed after 24 h of Saq-NO exposure, which correlated with increased expression of DR5. The biological relevance of this complex and powerful action of Saq-NO was consistent with the marked drug-induced inhibition of the growth of A375 xenotransplants in nude mice.

A rare pancreatic pseudoaneurysm in patient with acute pancreatitis and multiple myeloma.

The authors report the case of a 78-year old patient affected by multiple myeloma who develops acute pancreatitis and pseudoaneurysmal dilatation of the inferior pancreaticoduodenal artery causing erosion of the second portion of the duodenal wall and hematemesis. The authors focus first on the supposed etiological relationship between multiple myeloma and acute pancreatitis, and they assume that the therapeutic treatment for the bone marrow disease (bortezomib) may have triggered the pancreatic inflammatory response. They then analyze the pathogenesis of the vascular complication which seems to be related to the lytic action of pancreatic enzymes on the vessel wall which results in the formation of a pseudoaneurysm first and a pseudocyst then. The vascular complication was diagnosed by computed tomography (CT) thus avoiding selective angiography which was considered too invasive for the patient. The careful and conservative treatment of the complication has allowed for full healing of the cephalopancreatic region, in addition to avoiding surgery or embolization treatment of the pseudoaneurysm which is accompanied by a mortality rate as high as 50%.

Incidental rectal carcinoid discovered after stapled hemorrhoidopexy: importance of histopathologic examination.

AIM: Haemorrhoids are the most common surgically-treated gastrointestinal disorder. Complications of this surgery are generally non-neoplastic. Because rectal tumours usually present demonstratively during endoscopic examination, it is perhaps tempting to omit histopathologic examination after haemorrhoidectomy, especially in younger patients. METHODS: The AA present a case of an early rectal carcinoid discovered after surgical treatment of haemorrhoids in a 27 years old man as an example of why it is essential to send all such specimens in the pathologist. RESULTS: The detection of early lesions permits the adequate follow-up necessary to preclude more extensive surgery and eventually to prevent recurrence of tumour. CONCLUSION: All tissue resected by haemorrhoidopexy must be sent to the pathology laboratory to protect the life and health of the patient .

Thyroid surgery without cut and tie: the use of Ligasure for total thyroidectomy.

Total thyroidectomy is the surgical preferred procedure for the treatment of benign and malignant disease. The purpose of this research was to evaluate total thyroidectomy operation by Ligasure in comparison with total thyroidectomy by the traditional technique that uses clamp and tie. We evaluated 256 patients. In 144 patients (56%), we used Ligasure without tie for total thyroidectomy; in the remaining 112 patients (44%), we used clamp and tie. The middle values of the variables examined were inferior (P < 0.0005) in the Ligasure group compared with the clamp and tie group. Only the middle value of operating room costs was higher in the first group than in the second, balanced by a decreased hospital stay of two days. Ligasure can be safely used for total thyroidectomy, because there is a meaningful difference in the distribution of variance between the two groups. There are decreasing risks of parathyroid gland and laryngeal nerve injury in the Ligasure group.

[Intestinal obstruction from undiagnosed rectal and ileal endometriosis. Two clinical cases and review of the most recent literature]. / Sub-occlusione intestinale da insospettata endometriosi rettale ed ileale. Due casi clinici e revisione della più recente letteratura.

Deep endometriosis is a subserosal growth (for more than 5 mm) of funzional endometrial tissue outside the uterine cavity. Authors report two clinical cases of intestinal endometriosis localized in the anterior wall of the rectum and in the last ileal loop. Both cases were characterized by sub-occlusive symptoms, diagnosis performed by laparoscopy and surgical resection. Authors focus the various pathogenetic theories and dwell itself on the symptomatology often characterized by nonspecific abdominal symptoms such as chronic abdominal pain, sometimes in relation to the menstrual cycle, and intestinal disorders. If rectal bleeding is rare, more frequent are dysmenorrhea, dyspareunia and infertility may occur in up to 50% of patients. The diagnosis of intestinal endometriosis is very difficult and can be made by radiological methods (CT or MRI) or by endoscopic ultrasound only for the rectal localization but nowadays often the diagnosis is due to laparoscopic techniques. In the absence of guidelines the surgical therapy is not well defined. When is not necessary surgical emergency, according to the depth of endometriotic infiltration, elective surgery includes several surgical techniques both conservative and extensive such as segmental intestinal resection with hysterectomy and ovariectomy. In the most recent literature, finally, are reported over 50% of pregnancies after surgery

Giant hepatic hemangioma case report: When is it time for surgery?

We describe a case of a 30-year-old man who complained intermitted pain in right abdominal flank; a large cavernoumatos hemangioma - up to 6 cm in size - was revealed in the fifth hepatic segment using Ultrasonography and MRI (Magnetic Resonance Imaging). Indications for treatment - based on imaging features and clinical data - are briefly discussed in our report, providing also a review of existing literature.

Ultrasound-guided percutaneous treatment of abdominal collections.

Abdominal abscess is a very important problem nowadays, being responsible for prolonged hospitalisation, because these infections still cause substantial morbidity and mortality. For many years, surgical drainage has been considered the best therapeutic option in abdominal abscesses but several studies have subsequently shown that the percutaneous approach is as effective as surgical drainage. Starting from this background, the aim of this study was to evaluate whether or not percutaneous drainage is a valid treatment of choice. In the Department of Surgical Sciences, Organ Transplantation and Advanced Technologies of the University of Catania, 451 ultrasound guided percutaneous drainages of intra-abdominal abscesses were performed on 430 patients. Abscess drainage was successful in 322/403 (80%) of postoperative abscess, in 16/18 (90%) of primitive abscesses, in 10/12 cases (85%) of acute cholecystitis, in 3/6 cases (50%) of intrahepatic abscess and in 12/12 cases (100%) of pyelonephritis. US-guided drainage is currently the gold standard in the treatment of simple abdominal abscesses.

Predictive Value of the Number of Harvested Lymph Nodes and Cut-Off for Lymph Node Ratio in the Prognosis of Stage II and III Colorectal Cancer Patients.

Purpose/aim: The appropriate staging of colorectal cancer requires at least 12 lymph nodes to be sampled. We evaluated whether lymph node sampling (LNS) and lymph node ratio (LNR) can predict the prognosis of stage II-III patients. MATERIALS AND METHODS: This is a retrospective study on 432 patients classified in LNS ≥12 and LNS <12. Disease-free survival (DFS) was computed using the Kaplan-Meier method. We stratified stage III patients into 4 quartiles base on LNR values. To determine the optimal LNR cut-off, receiver operating characteristic (ROC) curve analysis was performed. RESULTS: There was a positive association between the number of lymph node sampled and the number of metastatic lymph nodes (p < 0.01). Among stage II patients, the DFS was 81% for LNS ≥ 12 and 72% for LNS < 12 (p = 0.158). Among stage III patients, the DFS was 58% (p < 0.001). We found a significant association between LNR quartiles and relapse in stage III patients but only in the LNS ≥ 12 group. ROC curve analysis indicated an ideal LNR cut-off value at 0.194 (sensitivity 65% and specificity 61%). The DFS of patients with LNR below 0.194 was 71%, and that of patients with LNR above 0.194 was 45% (log-rank test, p < 0.001). In the patients with LNS ≥ 12, the cut-off of 0.257 could predict recurrence (specificity 86%). CONCLUSIONS: Stage II patients with LNS < 12 tend to have shorter DFS than stage II patients with LNS ≥ 12. In stage III patients, an appropriate LNR cut-off is a better prognostic predictor than LNR quartile, especially in patients with LNS ≥ 12.

Effects of GIT-27NO, a NO-donating compound, on hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (H2O2), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the H2O2 on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.

Incarcerated Amyand's hernia: A case report.

INTRODUCTION: Inguinal hernia may contain vermiform appendix in very rare cases. This particular condition is known as Amyand's hernia and it has an incidence of 1%. Diagnosis is very difficult preoperatively, so it is usually an incidental finding. PRESENTATION OF CASE: We report a case of a 80 year old man with an irreducible mass in right inguinal region. During surgical procedure an Amyand's hernia was identified and we performed hernioplasty sec Trabucco and appendectomy. DISCUSSION: According to Losanoff and Basson classification, our case was type 1 and its management is very controversial. CONCLUSION: Surgical treatment depends on surgeon's experience and on clinical evaluation because there are many factors that may increase morbidity and mortality.

Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development.

Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets. This analysis revealed a group of 19 differentially expressed miRNAs. To establish the interaction between miRNAs and the most altered genes in CRC, the mirDIP gene target analysis was performed in such group of 19 differentially expressed miRNAs. To recognize miRNAs able to activate or inhibit genes and pathways involved in colorectal cancer development DIANA-mirPath prediction analysis was applied. Overall, these analyses showed that the up-regulated hsa-miR-183-5p and hsa-miR-21-5p, and the down-regulated hsa-miR-195-5p and hsa-miR-497-5p were directly related to colorectal cancer through the interaction with the Mismatch Repair pathway and Wnt, RAS, MAPK, PI3K, TGF-ß and p53 signaling pathways involved in cancer development.

The surgeon as a prognostic factor in the surgical treatment of rectal cancer.

Over the past 2 decades the surgeon and the hospital where he or she works have been considered to play an important role in the prognosis of the rectal cancer patients. The rate of sphincter-sparing rectal resection, local recurrence and survival are the factors more frequently utilized in the literature to evaluate if surgeons are able to affect the natural history of the rectal cancer. The quantitative aspect, high volume of the surgeon, is not enough but in order to achieve better results in the treatment of rectal cancer a specific interest in colorectal surgery is more important. While retrospective studies show a positive influence of the surgeon on the prognosis of these patients, prospective studies are very few so that we need to get more data to reach valid conclusions. The high number of rectal cancer patients does not allow a centralization of these patients into specialist Units, but we should get up everywhere colorectal programmes so that every department can reach a high standard of efficiency.

Anastomotic dehiscence after gastrectomy for cancer. Personal series.

BACKGROUND/AIMS: Nowadays the risk of anastomotic dehiscence after gastrectomy still exists. So the aim of this study was to analyze our experience regarding these anastomoses. METHODOLOGY: In our Surgical Unit, which is located in the Department of Surgical Sciences, Organ Transplantation and Advanced Technologies of the University of Catania, from January 1st 1985 to December 31st 2000, 249 patients underwent surgery for gastric cancer. RESULTS: We observed a statistically significant decrease of leaks in the third period of our study. CONCLUSIONS: These data demonstrate a significant decrease of anastomotic leaks with stapler in comparison to manual anastomoses.