Total thyroidectomy vs completion thyroidectomy for thyroid nodules with indeterminate cytology/follicular proliferation: a single-centre experience.

BACKGROUND: Despite total thyroidectomy (TT) is the most practiced procedure for a preoperatively diagnosed neoplastic lesion, according to the ATA guidelines, many surgeons perform completion thyroidectomy (CT) after hemithyroidectomy for patients with preoperative follicular proliferation/indeterminate cytology who are diagnosed with malignancy. CT has a higher complication rate than the primary procedure. The primary endpoint of our study is to compare the morbidity rate after CT with that after primary TT in patients with follicular proliferation/indeterminate cytology. METHODS: We retrospectively reviewed 237 patients who underwent thyroid surgery from 2009 to 2018 at our institution. We recruited only patients with follicular proliferation/indeterminate cytology and excluded those undergoing lymphadenectomies and thyroidectomies for benign pathology and staged thyroidectomies after intraoperative documentation of a RLN lesion. One hundred eighty-six of these patients underwent TT, and fifty-one underwent CT for the detection of differentiated thyroid cancer at the histological exam. RESULTS: No differences were found in the total complication rates between the two groups (OR 0,76, 95% CI 0.35-1.65, P = 0.49). We did not find any significant differences in the subgroup analysis. In particular, no significant differences were identified for transient hypocalcaemia (OR 1.17, 95% CI 0.44-3.11; P = 0,74), permanent hypocalcaemia (OR 1.04, 95% CI 0.21-5.18; P = 0,95), transient unilateral recurrent laryngeal nerve palsy (OR 0.78, 95% CI 0.21-2.81; P = 0,16), permanent unilateral recurrent laryngeal nerve palsy (OR 1.48, 95% CI 0.28-7.85; P = 0,61), and haematoma (OR 1,84, 95% CI 0,16-20,71; P = 0,61). CONCLUSIONS: CT following hemithyroidectomy can be performed with acceptable morbidity in patients with thyroid nodules with preoperative indeterminate cytology/follicular proliferation.

The prognostic value of KRAS and BRAF in stage I-III colorectal cancer. A systematic review.

BACKGROUND: Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. The aetiology of CRC is complex and involves interaction on environmental and genetic factors. The two most important pathways are the EGFR (Epidermal Grow Factor Receptor) signaling pathway, with the involvement of KRAS and BRAF, and the DNA mismatch repair (MMR). Generally, KRAS and BRAF mutations are mutually exclusive. They are both able to cause RAS/RAF/MAPK signaling pathway upregulation and are necessary for CRC development. BRAF mutations confers a poor prognosis in Western CRC patients, particularly in metastatic CRC (mCRC) and its mutations occur in approximately 4-20% CRC, with the vast majority being the V600E hotspot mutation. KRAS mutations are observed in 30- 40% CRC patients and act as predictive markers of resistance to epidermal growth factor receptor (EGFR)-targeted antibodies in metastatic CRC. Initial patient management is defined by TNM stage at diagnosis but in patient with stage II and III CRC, TNM staging alone does not predict outcome in CRC patients who may be eligible for adjuvant chemotherapy. Furthermore, for stage II and III, non-metastatic CRC patients, the prognostic role of BRAF and KRAS mutations is still controversial, particularly comparing microsatellite-unstable (MSI) and - stable tumors (MSS). The aim of this study was to clarify the impact of KRAS/BRAF mutations on prognosis in patients with stage I-III CRC. MATERIALS AND METHODS: A systematic review of literature was undertaken to evaluate the prognostic value of KRAS and BRAF mutations in stage I-III colorectal cancer. Four major databases (PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE LIBRARY) were searched. RESULTS: Ninety-two studies were identified. After screening of titles, abstract and inclusion criteria sixteen articles were included. Of the selected articles, five were prospective, ten were retrospectives studies, and one was a combined retrospective/ prospective study. CONCLUSION: In our opinion, a combination of molecular markers, tumor location with the other clinical-pathological variables and microsatellite status is essential to have a correct prognosis. Nevertheless, this combination could be useful as a predictive factor in stage I-III CRC. KEY WORDS: BRAF, Colorectal Cancer, KRAS, Stage I-III CRC, Translational research.

Sphincter-saving proctectomy for rectal cancer with NO COIL® transanal tube and without ostoma. Clinical outcomes, cost effectiveness and quality of life in the elderly.

BACKGROUND: Colorectal cancer is one of the most common invasive cancers, and it is responsible for considerable physical and psychosocial morbidity specially in older patients. However, only few reports focused on quality of life, cost-effectiveness and clinical outcomes of rectal cancer patients undergone to surgery. This retrospective study compares short-term and long-term outcomes in rectal cancer patients with more and less than 75 years of age. METHODS: Four hundred consecutive patients underwent radical surgery for rectal adenocarcinoma and they were collected in a prospective institutional database and divided into two groups: group 1 (≥75 years, N.=98); group 2 (<75 years, N.=302). Rectal anterior resection (RAR) with sphincter-saving restorative proctectomy and with application of silicone transanal tube NO COIL® 60-80 mm long, was the only procedure considered. Main clinical and pathological data were assessed and compared. RESULTS: Statistically significant differences between the two groups were detected regard to comorbidities and the emergency presentation. Overall survival is lower in patients over 75 age, but cancer-related survival is not different between the two groups. CONCLUSIONS: Although advanced age is associated with higher morbidity and mortality, in our experience, itself is not a contraindication for surgical sphincter-saving proctetomy in rectal cancer patients. The absence of a stoma also improved the cost effectiveness and patients' quality of life in both groups: psychological morbidity, sexuality, levels of anxiety and depression, body image.

Correction to: Next-generation sequencing analysis of receptor-type tyrosine kinase genes in surgically resected colon cancer: identification of gain-of-function mutations in the RET proto-oncogene.

In the publication of this article [1], there is an error in Fig. 7. The minus and plus signals are inverted which impairs understanding of the results described.

Identification of different mutational profiles in cancers arising in specific colon segments by next generation sequencing.

The objective of this study was to investigate the mutational profiles of cancers arising in different colon segments. To this aim, we have analyzed 37 colon cancer samples by use of the Ion AmpliSeq™ Comprehensive Cancer Panel. Overall, we have found 307 mutated genes, most of which already implicated in the development of colon cancer. Among these, 15 genes were mutated in tumors originating in all six colon segments and were defined "common genes" (i.e. APC, PIK3CA, TP53) whereas 13 genes were preferentially mutated in tumors originating only in specific colon segments and were defined "site-associated genes" (i.e. BLNK, PTPRD). In addition, the presence of mutations in 10 of the 307 identified mutated genes (NBN, SMUG1, ERBB2, PTPRT, EPHB1, ALK, PTPRD, AURKB, KDR and GPR124) were found to be of clinical relevance. Among clinically relevant genes, NBN and SMUG1 were identified as independent prognostic factors that predicted poor survival in colon cancer patients. In conclusion, the findings reported here indicate that tumors arising in different colon segments present differences in the type and/or frequency of genetic variants, with two of them being independent prognostic factors that predict poor survival in colon cancer patients.

Identification of copy number alterations in colon cancer from analysis of amplicon-based next generation sequencing data.

The objective of this study was to determine the feasibility to detect copy number alterations in colon cancer samples using Next Generation Sequencing data and to elucidate the association between copy number alterations in specific genes and the development of cancer in different colon segments. We report the successful detection of somatic changes in gene copy number in 37 colon cancer patients by analysis of sequencing data through Amplicon CNA Algorithm. Overall, we have found a total of 748 significant copy number alterations in 230 significant genes, of which 143 showed CN losses and 87 showed CN gains. Validation of results was performed on 20 representative genes by quantitative qPCR and/or immunostaining. By this analysis, we have identified 4 genes that were subjected to copy number alterations in tumors arising in all colon segments (defined "common genes") and the presence of copy number alterations in 14 genes that were significantly associated to one specific site (defined "site-associated genes"). Finally, copy number alterations in ASXL1, TSC1 and IL7R turned out to be clinically relevant since the loss of TSC1 and IL7R was associated with advanced stages and/or reduced survival whereas copy number gain of ASXL1 was associated with good prognosis.

Next-generation sequencing analysis of receptor-type tyrosine kinase genes in surgically resected colon cancer: identification of gain-of-function mutations in the RET proto-oncogene.

BACKGROUND: Improvement in genetic characterization of Colon Cancer (CC) patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are receptor tyrosine kinases (RTKs) whose role in CC need to be better investigated. METHODS: We have analysed 37 CC patients using the Ion AmpliSeq™ Comprehensive Cancer Panel (CCP). We have confirmed the somatic nature of RET variants through Sanger sequencing and assessed RET activation status and protein expression by immunofluorescence and western-blot analyses. We have used RET mutant expression vectors to evaluate the effect of selected mutations in HEK293 cells by performing proliferation, migration and clonogenic assays. RESULTS: Among the 409 cancer-related genes included in the CCP we have focused on the RTKs. Overall, we have observed 101 different potentially damaging variants distributed across 31 RTK genes in 28 patients. The most frequently mutated RTKs were FLT4, ROS1, EPH7, ERBB2, EGFR, RET, FGFR3 and FGFR4. In particular, we have identified 4 different somatic variants in 10% of CC patients in RET proto-oncogene. Among them, we have demonstrated that the G533C variant was able to activate RET by promoting dimer formation and enhancing Y1062 phosphorylation. Moreover, we have demonstrated that RET G533C variant was able to stimulate anchorage-dependent proliferation, migration and clonogenic cell survival. Notably, the effects induced by the RET G533C variant were abolished by vandetanib. CONCLUSIONS: The discovery of pathogenic variants across RTK genes in 75% of the CC patients under analysis, suggests a previously underestimated role for RTKs in CC development. The identification of a gain-of-function RET mutation in CC highlights the potential use of RET in targeted therapy.

Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated with Angiogenesis in Surgically-Treated Gastric Cancer Patients.

Mast cells and macrophages can play a role in tumor angiogenesis by stimulating microvascular density (MVD). The density of mast cells positive to tryptase (MCDPT), tumor-associated macrophages (TAMs), and MVD were evaluated in a series of 86 gastric cancer (GC) tissue samples from patients who had undergone potential curative surgery. MCDPT, TAMs, and MVD were assessed in tumor tissue (TT) and in adjacent normal tissue (ANT) by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and, in particular for TT, with important clinico-pathological features. In TT, a significant correlation between MCDPT, TAMs, and MVD was found by Pearson t-test analysis (p ranged from 0.01 to 0.02). No correlation to the clinico-pathological features was found. A significant difference in terms of mean MCDPT, TAMs, and MVD between TT and ANT was found (p ranged from 0.001 to 0.002). Obtained data suggest MCDPT, TAMs, and MVD increased from ANT to TT. Interestingly, MCDPT and TAMs are linked in the tumor microenvironment and they play a role in GC angiogenesis in a synergistic manner. The assessment of the combination of MCDPT and TAMs could represent a surrogate marker of angiogenesis and could be evaluated as a target of novel anti-angiogenic therapies in GC patients.

Bariatric Surgery and Rheumatic Diseases: A Literature Review.

BACKGROUND: Obesity is a debilitating growing condition and represents a challenge for every surgeon. It is associated with the activation of the inflammatory pathway and this may have a negative impact on the natural history of some rheumatic diseases. Bariatric surgery, reducing obesity, could bring to a minor activation of the well-known inflammatory pathway with improvement of these diseases. The aim of this review is to investigate the role of weight loss, achieved through bariatric surgery, in rheumatic diseases. MATERIALS AND METHODS: A systematic review of literature was undertaken to evaluate weight loss subsequent to bariatric surgery in obese patients suffering from some rheumatic diseases (Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis, Fibromyalgia, Osteoarthritis, Systemic Lupus Erythematous). Three major databases (PUBMED, EMBASE and WEB OF SCIENCE) were searched. RESULTS: Three-hundred studies were identified. After screening of titles, abstracts and inclusion criteria sixteen articles were included. Of the selected articles, seven were reviews, five were case reports, one was a clinical report, one was a retrospective study, one was a cohort study and one was an author manuscript. CONCLUSION: Weight loss, obtained through bariatric surgery, seems to reduce serum inflammatory markers as a consequence of the inflammatory pathway reduction and this is connected with both the improvement of some rheumatic diseases as well as with the reduction in the use of medicaments (steroids and immunosuppressors).

C-Kit receptor and tryptase expressing mast cells correlate with angiogenesis in breast cancer patients.

C-Kit protein is a transmembrane tyrosine kinase (TK) receptor (c-KitR-TK), which is predominantly expressed on mast cells (MCs) playing a role in tumor angiogenesis. It could be also expressed on epithelial breast cancer cells (EBCCs), but no data have been published regarding the correlation between mast cells positive to c-KitR (MCs-c-KitR), EBCCs positive to c-KitR (EBCCs-c-KitR), BC angiogenesis in terms of microvessel density (MVD) and the main clinic-pathological features. This study aims to evaluate the above parameters and their correlations in a series of selected 121 female early BC patients. It has been found a strong correlation between MVD and MCDPT, and MCs-c-KitR, MVD and MCs density positive to tryptase (MCDPT), and MCs-c-KitR and MCDPT by Pearson correlation. These data suggest an involvement of both MCDPT and MCs-c-KitR in BC tumor angiogenesis. Furthermore, BC tissue expressing c-KitR could be a putative predictive factor to c-KitR-TK inhibitors. In this way, selected patients with higher MCs-c-KitR could be candidate to receive c-KitR-TK inhibitors (e.g. masitinib, sunitinib) or tryptase inhibitors (e.g. nafamostat mesilate, gabexate mesilate).

The role of self-expandable metallic stents as "bridge to surgery" for the treatment of acute malignant colorectal obstruction. Our experience.

INTRODUCTION: Despite the widespread use of screening programs, the colorectal cancer occurs in 7-29% of cases with a bowel obstruction, needing an immediate decompression treatment by emergency surgery; unfortunately, the emergency surgery is characterized by high morbidity and mortality rates. The endoscopic placement of self-expandable metallic stents can be a useful alternative, allowing to decompress the acute obstruction in a short time, in order to correct dehydration, electrolytic imbalance and to improve the overall clinical conditions prior to adequately plan the intervention of elective surgery. AIM: The objective of our study was to evaluate the clinical success and potential complications related to the stent placement as "bridge to surgery". MATERIALS AND METHODS: Twenty-four patients with acute intestinal obstruction due to colorectal cancer were retrospectively observed in our Surgery Unit. They were selected only patients in whom technical success, defined as the correct placement of the stent, was recorded. All patients underwent a preoperative abdominal X-rays and whole body contrast- enhanced Computed Tomography (ceCT). Furthermore, an intraoperative fluoroscopy was also performed to obtain a better anatomical depiction of the lesions. The sites of obstruction were in the left colon (n=13) and in the proximal rectal tract (n=11). Covered and uncovered stents were placed respectively in 12 and 12 patients. The Over The Wire (OTW) technique has been used in 11 patients while the Through The Scope (TTS) technique in 13 subjects. All patients were brought to elective surgery in 5-10 days. The clinical success was defined as the resumption of normal bowel function within 48-72 hours and the absence of complications. RESULTS: Technical success was documented in 24 patients (100%). Clinical success was recorded in 17 patients (70.8%) while, in 7 patients, as treatment complications were recorded: 2 stent migrations (8.3%), 2 cases with tenesmus (8.3%), 2 bleeding (8.3%), 2 cases of abdominal pain (8.3%) and 1 case of perforation (4.2%), were recorded. CONCLUSION: In our series we found that placing self-expandable metallic stents, considered as "bridge to surgery", was a useful technique in the resolution of acute malignant colorectal obstructions, with high success rate and low rate of complications. KEY WORDS: Colorectal cancer, Clinical success, Large bowel obstruction, Radiology, Self-expanding metallic stent, Stenting, Surgery.

The density of mast cells c-Kit+ and tryptase+ correlates with each other and with angiogenesis in pancreatic cancer patients.

Literature data suggest that inflammatory cells such as mast cells (MCs) are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of well identified pro-angiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor. Nevertheless, few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed the correlation between mast cells positive to c-Kit receptor (c-Kit+ MCs), the density of MCs expressing tryptase (MCD-T) and microvascular density (MVD) in primary tumor tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC). A series of 35 PDAC patients with stage T2-3N0-1M0 (by AJCC for Pancreas Cancer Staging 7th Edition) were selected and then undergone to surgery. Tumor tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of number of c-Kit+ MCs, MCD-T and MVD. The above parameters were related each other and with the most important main clinico-pathological features. A significant correlation between c-Kit+ MCs, MCD-T and MVD groups each other was found by Pearson t-test analysis (r ranged from 0.75 to 0.87; p-value ranged from 0.01 to 0.04). No other significant correlation was found. Our in vivo preliminary data, suggest that tumor microenvironmental MCs evaluated in terms of c-Kit+ MCs and MCD-T may play a role in PDAC angiogenesis and they could be further evaluated as a novel tumor biomarker and as a target of anti-angiogenic therapy.

Bridge to surgery in patients with obstructive colorectal cancer Comparison of covered and uncovered stents.

AIM: Placement of self-expandable metallic stent has been used for bridge to surgery in the treatment of colorectal obstruction. Our aim was to compare technical success and complication rates of covered and uncovered inserted stents in colorectal malignant obstruction patients. MATERIAL OF STUDY: A series of 24 obstruction colorectal cancer patients were selected and included in the study for endoscopic stenting as a bridge to surgery: group 1 (patients with covered stents, n =12); group 2 (patients with uncovered stents, n=12). Technical success and complication rates of all procedures were compared between covered and uncovered stents. RESULTS: Stent placement was technically successful in all patients with no procedure-related complications. No significant differences between the two groups were found (p-value > 0.05). Complications were observed after the technical success. CONCLUSIONS: Our preliminary data suggest that self-expandable metallic stent is a safe and efficacy approach in patients with malignant colorectal obstruction for bridge to surgery and there are not differences in the use of covered or uncovered stents due to low complication rates and positive outcomes in both groups. KEY WORDS: Bridge to Surgery, Colorectal Cancer, Emergency Obstruction, Stents.

Tryptase mast cell density, protease-activated receptor-2 microvascular density, and classical microvascular density evaluation in gastric cancer patients undergoing surgery: possible translational relevance.

BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via protease-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. Nevertheless, no data are available concerning the relationship among tryptase MC density (TMCD), endothelial cells (ECs) positive to PAR-2 microvascular density (PAR-2-MVD) and classical MVD (C-MVD) in gastric cancer (GC) angiogenesis. METHODS: In this study, we analyzed the correlation of TMCD, PAR-2-MVD, C-MVD with each other and with the main clinicopathological features in GC patients who underwent surgery. A series of 77 GC patients with stage T2-3N2-3M0 (classified by the American Joint Committee on Cancer for Gastric Cancer, 7th edition) were selected and then underwent surgery. RESULTS: Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of numbers of TMCD, PAR-2-MVD and C-MVD. A significant correlation between the TMCD, PAR-2-MVD and C-MVD groups with each other was found by Pearson t-test analysis (r ranged from 0.64 to 0.76; p value ranged from 0.02 to 0.03). There was no other significant correlation between the above parameters and clinicopathological features. CONCLUSIONS: Our in vivo preliminary data suggest that TMCD and PAR-2-MVD may play a role in GC angiogenesis and they could be further evaluated as a target of antiangiogenic therapy.

The care of transmetatarsal amputation in diabetic foot gangrene.

Diabetic foot ulcerations may determine minor or major amputation, with a high impact on patients' life expectation and quality of life and on economic burden. Among minor amputations, transmetatarsal amputation (TMA) appears to be the most effective in terms of limb salvage rates and in maintaining foot and ankle biomechanics. In spite of this, TMA needs particular pre- and postoperative management in order to avoid the frequent failure rates. A systematic review was undertaken of studies concerning TMA and its care in diabetic foot gangrene. Studies were identified by searching the MEDLINE, Scopus and Science Direct databases until 13 January 2016. All studies were assessed using the Downs and Black quality checklist. Of the 348 records found, 86 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 35 manuscripts because of the following reasons: (1) no innovative or important content, (2) no multivariable analysis, (3) insufficient data, (4) no clear potential biases or strategies to solve them, (5) no clear endpoints and (6) inconsistent or arbitrary conclusions. The final set included 51 articles. In the current literature, there are less data about TMA, indication for the selection of patients, outcomes and complications. Generally, the judgment of an experienced physician is one of the best indicators of subsequent healing. Ankle brachial indices, toe pressures, laser Doppler skin perfusion pressures, angiography and Doppler assessment of foot vasculature may help physicians in this decision. In any case, despite the presumed lower healing rate, it is reasonable to pursue a TMA in a patient with a higher likelihood of continued ambulation. Furthermore, tailored wound closure, adjuvant local treatments and the choice of the most appropriate antibiotic therapy, when infection occurs, are pivotal elements for the success of TMA procedures. TMA is a valuable option for diabetic foot gangrene that can prevent major limb loss and minimise loss of function, thus improving the quality of life for diabetic patients.

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery.

Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2-3N2-3M0 (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

Single incision laparoscopic cholecystectomy in geriatric patients.

BACKGROUND: Laparoscopy is a surgical approach recommended for the treatment of gall bladder disease. It is recommended also in geriatric patients. Recently Single Incision Laparoscopic Cholecystectomy (SILC) has been proposed to minimize surgical trauma, recovery and hospitalization time. However, the results and advantages of SILC in the geriatric population have received minimal attention. This case series review is focused on the results of SILC in the geriatric population. METHODS: The records of 355 patients who had undergone SILC were reviewed. This report identifies, in the entire cohort, 40 patients aged 65 years or older at the time of surgery who will be the object of this study (geriatric series). Clinical outcomes and results were evaluated. Moreover, post-operative pain of the geriatric cohort was compared to that of the entire series. RESULTS: SILC was successfully completed for 347 out of 355 patients of the entire series, with no mortality reported. In total SILC was converted to standard laparoscopy in 10 patients (2.2%) but never to open procedure. No significant difference was found between the total cohort and the geriatric series in terms of median time of operation (61.20 min vs 68.38 min). Post-operative pain was significantly lower in geriatric patients. CONCLUSION: SILC is an effective and safe procedure for the treatment of gallbladder disease of elderly, also in terms of post-operative pain and it represents an alternative to the standard laparoscopic approach on a routine basis.

Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery.

BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase phosphorylation. Nevertheless, no data are available concerning the relationship between MC density positive to tryptase (MCDPT), endothelial cells positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the main clinicopathological features, in early HCC patients who underwent surgery. METHODS: A series of 53 HCC patients with early stage (stage 0 according to the Barcelona Clinic Liver Cancer Staging Classification) were selected and then underwent surgery. Tumor tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR-2-MVD, and C-MVD. RESULTS: A significant correlation between MCDPT, PAR-2-MVD, and C-MVD groups, each correlated to the others, was found by Pearson t-test analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other significant correlation was found. CONCLUSION: Our in vivo pilot data suggest that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further evaluated as a target of antiangiogenic therapy.

Multivisceral resection for occlusive colorectal cancer: Is it justified?

BACKGROUND: The only possibility of curative surgery in primary T4, locally advanced, adherent colorectal carcinoma (LAACRC) or recurrent disease with infiltration of adjacent organs is the en bloc resection of the invaded structures to achieve clear surgical margins (R0). The role of extended resections for occlusive LAACRC remains unclear. We report on our experience on Multivisceral resections (MVR) for LAACRC patients between 2003 and 2012. METHODS: Twenty-two patients, who were treated with MVR with curative purpose for non-metastatic disease were recruited. General epidemiologic data, clinical findings, surgical treatment and/or multimodal therapy, histo-pathological examination and follow-up were collected. In addition post-operative complications were classified. Patients with occlusive LAACRC (n = 6) were compared to patients with uncomplicated presentation (n = 16) defined according to the UICC classification. RESULTS: No statistically significant differences were observed between the two groups, in terms of median age, gender and localization of tumors. R0 resection was performed in 14 (87.5%) patients with uncomplicated tumors and in all patients with occlusive LAACRC. R1 resection was performed in 2/16 (12.5%) patients with uncomplicated disease. No peri-operative mortality was reported in patients of both groups. In the group of uncomplicated tumors, 11 patients (68.7%) were classified as pathological (p)T4 and 5 patients (31.2%) were classified pT3 whereas in the group of occlusive LAACRC the majority of patients were classified as pT4 (83.3%). Lymph node involvement occurred in 9 patients (56.2%) of the fist group and in two patients (33.3%) of the second group, respectively. The 3-year survival rates in all patients with both uncomplicated and occlusive diseases were 58.4% and 33.3%, respectively. The 3-years survival of patients with locally advanced adherent rectal cancer was significantly lower than the observed survival of patients with colon cancer (p < 0.0001). CONCLUSION: MVR offers cure (R0 resections) in uncomplicated and obstructive LAACRC with three years survival in 40% of patients. Patients affected by rectal cancer with occlusive disease showed significantly decreased survival in comparison with those affected by colon cancer.

Mast Cell-Targeted Strategies in Cancer Therapy.

Mast cells (MCs) are cells that originate in the bone marrow from pluripotent CD34+ hematopoietic stem cells. Precursors of MCs migrate through the circulation to their target tissues, completing their maturation process into granulated cells under the influence of several microenvironment growth factors. The most important of these factors is the ligand for the c-Kit receptor (c-Kit-R) namely stem cell factor (SCF), secreted mainly by fibroblasts and endothelial cells (ECs). SCF also regulates development, survival and de novo proliferation of MCs. It has already been demonstrated that gain-of-function mutations of gene c-Kit encoding c-Kit-R result in the development of some tumors. Furthermore, MCs are able also to modulate both innate and adaptive immune response and to express the high-affinity IgE receptor following IgE activation. Among the other IgE-independent MC activation mechanisms, a wide variety of other surface receptors for cytokines, chemokines, immunoglobulins, and complement are also described. Interestingly, MCs can stimulate angiogenesis by releasing of several pro-angiogenic cytokines stored in their cytoplasm. Studies published in the last year suggest that angiogenesis stimulated by MCs may play an important role in tumor growth and progression. Here, we aim to focus several biological features of MCs and to summarize new anti-cancer MC-targeted strategies with potential translation in human clinical trials.