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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. [ABSTRACT FROM AUTHOR]

Summary: 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. [Copyright &y& Elsevier]

Summary: Follow-up of surgically treated colorectal cancer patients is not supported by objectively certain data. Despite the thousands of investigations reported in the scientific literature, only six randomized prospective studies and two meta-analysis of randomized studies provide data suggesting clear conclusions. Our review of the literature revealed that intensive colorectal follow-up should be performed even if the long-term survival benefit is small. The timing and investigations conducted in follow-ups diverge. The inconsistency of follow-ups is revealed by the fact that the leading USA and European societies propose different guidelines. One datum that the literature agrees on is that pancolonoscopy performed at 3–5 year intervals in colorectal cancer surgery patients supports diagnosis of adenomatous polyps and metachronous cancers. Cost analysis have shown that intensive follow-up would certainly exceed the cut-off point level set for every additional year of good quality of life. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Extragastrointestinal stromal tumors (EGISTs) are a rare subgroup of gastrointestinal stromal tumors (GISTs), arising from outside the walls of gastrointestinal tubular organs. We report a case of an EGIST of the lesser omentum that represented a diagnostic challenge. Due to its atypical radiologic findings, it was preoperatively mistaken for pedunculated hepatic hemangioma. Histopathologically, it showed epithelioid structure and c-kit negative, very uncommon for GIST. Only a few cases of EGISTs have been previously reported. We discuss imaging and histological features, emphasizing potential pitfalls. [ABSTRACT FROM AUTHOR]

This paper presents our experience in the treatment of a patient affected by metastatic esophagogastric junction cancer with a high tumor burden and an incipient visceral crisis. The patient was treated with a combination of induction taxane-based chemotherapy, local radiotherapy and microwave ablation of residual liver metastases. The patient experienced a complete and durable response with long-term survival of more than 3 years, without any relevant acute or late side effects. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous neoplasms (IPMNs) represent a group of cystic pancreatic neoplasms with large range of clinical behaviours, ranging from low-grade dysplasia or borderline lesions to invasive carcinomas. They can be grouped into lesions originating from the main pancreatic duct, main duct IPMNs (MD-IPMNs), and lesions which arise from secondary branches of parenchyma, denominated branch-duct IPMNs (BD-IPMNs). Management of these cystic lesions is essentially based on clinical and radiological features. The latter have been very well described in the last fifteen years, with many studies published in literature showing the main radiological features of IPMNs. Currently, the goal of imaging modalities is to identify "high-risk stigmata" or "worrisome feature" in the evaluation of pancreatic cysts. Marked dilatation of the main duct (>1cm), large size (3-5 cm), and intramural nodules have been associated with increased risk of degeneration. BD-IPMNs could be observed as microcystic or macrocystic in appearance, with or without communication with main duct. Their imaging features are frequently overlapped with cystic neoplasms. The risk of progression for secondary IPMNs is lower, and subsequently an imaging based follow-up is very often proposed for these lesions. [ABSTRACT FROM AUTHOR]

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. J. Cell. Physiol. 226: 1803-1812, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Pseudomyxoma is a rare disease characterized by the accumulation of mucus in the abdominal cavity. It is generally caused by a malignant tumour or peritoneal implantation from ruptured benign cysts or appendicular disease. The Mucus sets on the peritoneal surface and successively it stratifies onto organs. Successively its solidification could give compression on vascular structures, hepatic hilum and intestinal ansae. We report a case of a male patient 65 years old who came in under observation in March 2001. The patient stated he had an abdominal pain in the right iliac *fossa (che cosè??) three months before and since then he had had many episodes of abdominal pain. CT scan demonstrated the presence of a big gelatinous mass, which involved the abdominal cavity. The patient underwent surgical operation in which were made cholecystectomy, omentectomy, peritonectomy, total colectomy and extirpation of surgical surface also an intraoperative hyperthermic chemoterapy for 30 minutes was carried out. The patient had no complications and was discharged 10 days after surgery. By now, 72 months after surgery the patient is well and without disease. Peritoneal pseudomixoma is a very rare pathology. In our opinion surgery is the best treatment associated to an intraoperative hyperthermic chemotherapy and an adjuvant chronomodulated systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Acquaviva R, Lanteri R, Li Destri G, Caltabiano R, Vanella L, Lanzafame 8, Di Cataldo A, Li Volti G, Di Giacomo C. Beneficial effects of rutin and L-arginine coadministration in a rat model of liver ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 296: G664-G670, 2009. First published December 24, 2008; doi: 10.1152/ajpgi.90609.2008.-Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) hR. 3) hR + rutin, 4) hR + L-arginine, and 5) YR + rutin + L-arginlne. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated YR rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in YR rats reduced hepatic damage. Interestingly, combined therapy with rutin and Larginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and Larginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol. [ABSTRACT FROM AUTHOR]

Background: Twenty-five percent of radically treated colorectal cancer patients already have occult hepatic metastases (OHM) that will later be observed during postoperative follow-up. Instrumental examinations, i.e., intraoperative ultrasound or Doppler perfusion index, have not improved diagnosis. As carcinoembyonic antigen (CEA) levels are useful to reveal hepatic metastases from colorectal cancer, determination of CEA in the bile rather than the blood may allow preclinical diagnosis of OHM thanks to the reduced volume of bile. Methods: One hundred radically treated colorectal cancer patients were enrolled in the study. Bile was withdrawn from the gallbladder intraoperatively and biliary CEA levels determined using an immuno-enzymatic method (normal value 0-5 ng/ml). Eighty-nine fully evaluable patients were followed up for three years postoperatively to monitor hepatic metastases. Preoperative blood CEA, lymph node metastases and biliary CEA were compared in order to assess which procedure was more efficient in identifying patients who would develop hepatic metastases. Results: Eleven of the 89 evaluable patients developed hepatic metastases: 9/11 presented elevated biliary CEA levels (mean: 12.73; range: 5.1-26.2); 8/11 had high preoperative blood CEA values; and 9/11 were at anatomopathological stage N+. In the 78 patients who did not develop hepatic metastases, biliary CEA was within normal limits in 73/78, preoperative blood CEA was normal in 60/78, and 58/78 patients were at anatomopathological stage N-. Hence, the sensitivity of biliary CEA was 81.8%, specificity was 93.6%, and diagnostic accuracy was 92.1%. Conclusions: Determination of biliary CEA seems to be more efficient in identifying patients presenting OHM who require frequent clinical examinations or adjuvant cancer treatment. [ABSTRACT FROM AUTHOR]

Leiomyosarcoma of the inferior cava vein is a rare clinical entity and according to the literature has been described in less than 300 patients. C.S., 54 yrs old, male, artisan, came to our observation in March 2005 for abdominal pain (upper right quadrant) and asthenia. Ultrasound demonstrated the presence of a gallbladder lithiasis and an echogenic mass, 7 x 8 cm, in retroperitoneal space, behind the liver. Computed tomography confirmed the presence of the mass apparently originating from middle cava vein. This mass displaced duodenum, common bile duct and pancreatic head. Doppler examination demonstrated the permeability of cava vein. Mass was resected together with anterior wall of the cava vein. Histological finding demonstrated an encapsulated high-grade leiomyosarcoma (Ki67/Mib1 index: 20%, alfa-actin positive, desmin positive, h-caldesmon positive). Leiomyosarcoma of the inferior cava vein is a rare, potentially aggressive neoplasma. Nowadays, surgery performed by an interdisciplinary team represents gold standard treatment, even if adjuvant therapy role should be demonstrated. [ABSTRACT FROM AUTHOR]

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. Case summary: 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. [ABSTRACT FROM AUTHOR]