Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn's disease.

Single cell RNA sequencing of human full thickness Crohn's disease (CD) small bowel resection specimens was used to identify potential therapeutic targets for stricturing (S) CD. Using an unbiased approach, 16 cell lineages were assigned within 14,539 sequenced cells from patient-matched SCD and non-stricturing (NSCD) preparations. SCD and NSCD contained identical cell types. Amongst immune cells, B cells and plasma cells were selectively increased in SCD samples. B cell subsets suggested formation of tertiary lymphoid tissue in SCD and compared with NSCD there was an increase in IgG, and a decrease in IgA plasma cells, consistent with their potential role in CD fibrosis. Two Lumican-positive fibroblast subtypes were identified and subclassified based on expression of selectively enriched genes as fibroblast clusters (C) 12 and C9. Cells within these clusters expressed the profibrotic genes Decorin (C12) and JUN (C9). C9 cells expressed ACTA2; ECM genes COL4A1, COL4A2, COL15A1, COL6A3, COL18A1 and ADAMDEC1; LAMB1 and GREM1. GO and KEGG Biological terms showed extracellular matrix and stricture organization associated with C12 and C9, and regulation of WNT pathway genes with C9. Trajectory and differential gene analysis of C12 and C9 identified four sub-clusters. Intra sub-cluster gene analysis detected 13 co-regulated gene modules that aligned along predicted pseudotime trajectories. CXCL14 and ADAMDEC1 were key markers in module 1. Our findings support further investigation of fibroblast heterogeneity and interactions with local and circulating immune cells at earlier time points in fibrosis progression. Breaking these interactions by targeting one or other population may improve therapeutic management for SCD.

Epigenetic and metabolic reprogramming of fibroblasts in Crohn's disease strictures reveals histone deacetylases as therapeutic targets.

BACKGROUND & AIMS: No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterised fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies. METHODS: We undertook immunohistochemistry, metabolic, signalling pathway and Epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/ NSCD fibroblasts were cultured with TGFß and valproic acid [VPA]. RESULTS: Stricturing CD was characterised by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFß-stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appear "metabolically primed" and responded more strongly to both TGFß and VPA. Treatment with VPA revealed TGFß-dependent and independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters. CONCLUSIONS: Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFß-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis.

Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.

Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor ß1 (TGFß) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. ß-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFß signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in ß-catenin-positive cells. In vitro, activation of Wnt-ß-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of ß-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFß increased ß-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFß up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a ß-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFß signalling pathways in CD intestinal fibrosis.

Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours.

BACKGROUND: The prognostic significance of lymph nodes (LNs) metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours (GEP NETs) undergoing curative resection is still debatable. Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy. AIM: To evaluate the effect of lymph node (LN) status and yield on relapse-free survival (RFS) and overall survival (OS) in patients with resected GEP NETs. METHODS: Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively. Grade 3 tumours (Ki67 > 20%) were excluded. Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS. RESULTS: A total of 217 patients were included in the study. The median age was 59 years (21-97 years) and 51% (n = 111) were male. Primary tumour sites were small bowel (42%), pancreas (25%), appendix (18%), rectum (7%), colon (3%), gastric (2%), others (2%). Median follow up times for all patients were 41 mo (95%CI: 36-51) and 71 mo (95%CI: 63-76) for RFS and OS respectively; 50 relapses and 35 deaths were reported. LNs were retrieved in 151 patients. Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients. Three or more positive LNs were detected in 62 cases. The result of univariate analysis suggested perineural invasion (P = 0.0023), LN positivity (P = 0.033), LN retrieval of ≥ 8 (P = 0.047) and localisation (P = 0.0049) have a statistically significant association with shorter RFS, but there was no effect of LN ratio on RFS: P = 0.1 or OS: P = 0.75. Tumour necrosis (P = 0.021) and perineural invasion (P = 0.016) were the only two variables significantly associated with worse OS. In the final multivariable analysis, localisation (pancreas HR = 27.33, P = 0.006, small bowel HR = 32.44, P = 0.005), and retrieval of ≥ 8 LNs (HR = 2.7, P = 0.036) were independent prognostic factors for worse RFS. CONCLUSION: An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery. Removal of ≥ 8 LNs is associated with increased risk of relapse, which could be due to high rates of LN positivity at the time of surgery. Given that localisation had a significant association with RFS, a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres.

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined. AIM: To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN. METHODS: Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres. Patient data were retrospectively collected from medical records. Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN. Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1. Kaplan-Meier analysis was applied to estimate survival outcomes. Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions (univariate) and Cox-regression analysis (multivariable). RESULTS: Sixty-nine consecutive patients identified; Median age at diagnosis: 64 years. Males: 63.8%. Localised disease (curable): 53.6%. Commonest sites of origin: colon-rectum (43.5%) and oesophagus/oesophagogastric junction (15.9%). The neuroendocrine component was; predominant in 58.6%, poorly differentiated in 86.3%, and large cell in 81.25%, of cases analysed. Most distant metastases analysed (73.4%) were occupied only by a poorly differentiated neuroendocrine component. Ninety-four percent of patients with localised disease underwent curative surgery; 53% also received perioperative treatment, most often in line with protocols for adenocarcinomas from the same sites of origin. Chemotherapy was offered to most patients (68.1%) with advanced disease, and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion. In localised cases, median recurrence free survival (RFS); 14.0 mo (95%CI: 9.2-24.4), and median overall survival (OS): 28.6 mo (95%CI: 18.3-41.1). On univariate analysis, receipt of perioperative treatment (vs surgery alone) did not improve RFS (P = 0.375), or OS (P = 0.240). In advanced cases, median progression free survival (PFS); 5.6 mo (95%CI: 4.4-7.4), and median OS; 9.0 mo (95%CI: 5.2-13.4). On univariate analysis, receipt of palliative active treatment (vs best supportive care) prolonged PFS and OS (both, P < 0.001). CONCLUSION: MiNEN is most commonly driven by a poorly differentiated neuroendocrine component, and has poor prognosis. Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.

(1) H-MR spectroscopy characterization of the adipose tissue associated with colorectal tumor.

PURPOSE: To investigate colorectal tumor by looking at the lipid tissue around the lesion. Adipose tissue is not only an inert storage system for excess calories, but is involved in several pathological processes linked to tumor development. MATERIALS AND METHODS: We obtained 24 colorectal specimens after surgical excision from patients affected by colorectal cancer at different tumor stages. (1) H-MR spectoscopy (MRS) spectra were collected from two voxels, in proximity of the lesion and far from it, in each specimen with a preclinical scanner. We differentiated patients by pathological tumor stage, and we compared the chemical composition of adipose tissue between patient groups, both close the tumor and far from it. RESULTS: Monounsaturated fatty acids (MUFA) close the lesion are increased at higher tumor stages, while MUFA far from the lesion do not follow this trend. This study is really explorative due to the small numbers of subjects and we are cautious on the interpretation of the results. However, the approach of the present work allows a further insight in the tumor characterization. CONCLUSION: Looking at the lipid tissue around a lesion through (1) H-MRS can return important information regarding its genesis and development.

Proton magnetic resonance spectroscopy: ex vivo study to investigate its prognostic role in colorectal cancer.

BACKGROUND: Proton Magnetic Resonance Spectroscopy (1H MRS) is used for clinical diagnosis in some tumours. The aim of this study is to explore ex vivo the potential of 1H MRS in identifying malignancy through metabolic markers in the perspective of its application in all cases of difficult diagnosis and after neoadjuvant treatment. METHODS: Spectroscopy was performed ex vivo on 29 colorectal specimens. All patients were staged with imaging, underwent radical surgery and then followed-up. Spectral quantification analysis of components expressed in colorectal tumours and in healthy mucosa were evaluated. The MRS-tumour marker (MRS-tm) was calculated for each case. The U-test was used to compare MRS-tm in tumours and in healthy mucosa. In order to select a cut-off for MRS-tm in the tumour and healthy mucosa and to distinguish patients who were disease-free or with recurrence-progression, we performed the ROC curve analysis. RESULTS: In the 24 subjects without neoadjuvant treatment, it was found that MRS-tm is able to discriminate healthy and neoplastic tissue and can discriminate patients with risk of recurrence/progression CONCLUSION: Our data seem to show that 1H MRS may be successfully applied in vivo non-invasively to differentiate tumours from healthy mucosa and could also distinguish patients with different prognoses.

F-18 FDG PET/CT in rectal carcinoma: where are we now?

This short review aims at summarizing the available data pertaining to the usefulness of F-18 FDG PET/CT in rectal cancer. It is specifically focused on the emerging role of F-18 FDG PET/CT in assessing the response to neoadjuvant combined radiochemotherapy in locally advanced rectal cancer. It also probes the possibility of finding standardized PET/CT parameters that are capable of differentiating responders from nonresponders in whom therapeutic approach could be modified.

Treatment for retained [corrected] common bile duct stones during laparoscopic cholecystectomy: the rendezvous technique.

OBJECTIVE: To determine the feasibility and efficacy of the laparoscopic intraoperative rendezvous technique for common bile duct stones (CBDS). DESIGN: Case series. SETTING: Verona University Hospital, Verona, Italy. PATIENTS: A total of 110 patients were enrolled in the study; 47 had biliary colic; 39, acute cholecystitis; 19, acute biliary pancreatitis; and 5, acute biliary pancreatitis with associated acute cholecystitis. INTERVENTIONS: In all patients, CBDS diagnosis was reached by intraoperative cholangiography. Intraoperative endoscopy with rendezvous performed during laparascopic cholecystectomy for confirmed CBDS; for such a procedure, a transcystic guide wire was positioned into the duodenum. Intraoperative endoscopy with rendezvous was performed for retrieved CBDS during a laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Laparoscopic rendezvous feasibility, morbidity, postprocedure pancreatitis, and mortality. RESULTS: The laparoscopic rendezvous proved to be feasible in 95.5% (105 of 110 patients). The rendezvous failed in 3 cases of successfully performed laparoscopic cholecystectomy, and a conversion of the laparoscopy was needed in 2 cases of successful rendezvous. Two major complications and 2 cases of bleeding were registered after sphincterotomy was successfully performed with rendezvous, and severe acute pancreatitis complicated a traditional sphincterotomy performed after a failed rendezvous. CONCLUSIONS: Rendezvous is a feasible option for treatment of CBDS; it allows one to perform only 1 stage of treatment, even in acute cases such as cholecystitis and pancreatitis. Positioning of the guide wire may allow reduced complications secondary to papilla cannulation but not those of the endoscopic sphincterotomy.

Minimally invasive treatment of portal hypertension, abdominal aortic aneurysm, and colon cancer: a case report.

Surgical therapy in cirrhotic patients has high morbidity and mortality. Hepatic function and complexity of surgical procedures strongly influence postoperative results. We report the case of a cirrhotic patient with portal hypertension, abdominal aortic aneurysm (AAA), and right colon cancer. After neoadjuvant transjugular intrahepatic portosystemic shunt, we performed 1-stage endovascular aneurysm repair and laparoscopic right colectomy. Minimally invasive surgery allows the effective treatment of high-risk patients with severe comorbidities that some years ago would not have been operated on.

Perianal Paget's disease: presentation of six cases and literature review.

PURPOSE: Extramammary Paget's disease (EMPD) is frequently associated with adnexal or visceral synchronous or metachronous malignancies. Our purpose was to evaluate, retrospectively, the results obtained in six cases of EMPD and to review the literature. METHODS: Six patients with the perianal Paget's disease had been treated in our division between March 1996 and December 2006. In three cases, the disease was confined in the epidermis; in one case, there was a microinvasion of the dermis, while in another one the dermis was infiltrated. The last case was associated to a low rectal adenocarcinoma. All patients underwent wide perianal excision and reconstruction with skin graft. We performed a transanal resection of the rectal adenocarcinoma. A review of the literature from 1990 to 2008 revealed 193 cases of perianal EMPD, 112 were intraepithelial/intradermal while 81 were associated with malignancies. Anorectal adenocarcinoma was already existing in two cases, synchronous in 48, and subsequent to diagnosis in 11. RESULTS: In three cases, the disease recurred locally, but no patient developed metastatic spread. Five patients survived and are free of disease. The review of the literature allows a clear identification of the primitive EMPD and the form associated to anorectal adenocarcinoma and little information about cases associated with synchronous adnexal adenocarcinoma. The Paget's disease can relapse after radical surgery and has a capacity of metastatic spread. CONCLUSIONS: Up to now, no clear guidelines have been established for the diagnosis of EMPD. The association with synchronous or metachronous carcinomas imposes a long-term follow-up with frequent clinical, radiological, and endoscopical controls.

[Prognostic significance of the Mandard TRG classification after induction therapy in carcinoma of the oesophagus and cardia]. / Significato prognostico della classificazione TRG di Mandard dopo terapia induttiva nel carcinoma di esofago e cardias.

Mandard's tumor regression grade (TRG) is widely used to evaluate the pathological response to induction therapy with concurrent chemoradiotherapy in cancer of the oesophagus or gastro-oesophageal junction. The aim of this study was to evaluate the prognostic significance and clinical applicability of TRG. From 2000 to 2007, 108 patients with squamous cell carcinoma of the oesophagus (57 cases) or Siewert type I and II adenocarcinoma of the cardia (51 cases) were treated with induction chemoradiotherapy followed by surgery in the 1st Division of General Surgery of the University of Verona. The treatment was identical for all patients and consisted of cisplatin, 5 FU and docetaxel together with 50 Gy of concurrent radiotherapy. The treatment-induced response was evaluated by TRG. Fifty-one, 24, 17, 9 and 7 patients were classified, respectively, as TRG1, 2, 3 4 and 5. Fifty-two patients died of the disease. Disease-related survival decreased with the increase in TRG class in node-negative patients (p < 0.001), while in N+ patients it was poor, irrespective of TRG class (p = 0.241). Mandard TRG is therefore useful for staging patients undergoing preoperative chemoradiotherapy, because it displays high prognostic significance. In our study, however, N was the main prognostic factor and for this reason it is mandatory to consider nodal status along with TRG. Moreover, among N negative patients, the prognosis of each different TRG class is statistically different and for this reason different TRG classes cannot be grouped together.

Significance of super-extended (D3) lymphadenectomy in gastric cancer surgery.

BACKGROUND: The extension of lymphadenectomy is a matter of debate in gastric cancer surgery. The purpose of the present study was to analyse our experience on D3 lymphadenectomy in the treatment of gastric cancer with special reference to post-operative morbidity and mortality, incidence of para-aortic nodal metastases and long-term prognosis. METHODS: The results of 201 patients who underwent potentially curative gastrectomy with D3 lymphadenectomy for non-metastatic gastric adenocarcinoma at the First Department of General Surgery, University of Verona, from January 1988 to December 2004, were analysed statistically. The analysis did not include gastric stump and linitis plastica type tumors. RESULTS: Twenty-six out of the 201 patients (12.9%) showed para-aortic nodal metastases. Para-aortic node involvement was significantly higher in upper third tumors (29.1%) with respect to middle (6.1%) and lower third (7.5%) (P<0.001). Sixty-two patients (30.8%) developed post-operative complications with pulmonary affections (7%), pancreatic fistulas (4.5%) and abdominal abscesses (4.5%) as the most frequently observed complaints. In-hospital mortality was 1.5%. Overall 5-year survival rate for R0-patients was 53.6%. Considering survival in relation to nodal involvement, interestingly, patients with non-regional lymph node metastases (M1a) showed a slightly better prognosis with respect to pN3 patients (3-year survival: 13.9% and 19.4% for pN3 and M1a classes, respectively). CONCLUSIONS: D3 lymphadenectomy should be considered in curative surgery for advanced gastric cancer, especially for upper third tumors, with an acceptable morbidity and no increase in mortality. Further studies with a larger number of patients are required to confirm its prognostic value.

Abdominal aortic endograft infection: report of two cases and review of the literature.

Endovascular prosthesis infection after exclusion of an abdominal aortic aneurysm is a rare, dramatic event and its diagnosis and treatment are extremely complex. This particular complication has been less well explored in the literature than others such as endoleaks, migration or stent rupture. The incidence of aorto-iliac stent-graft infection is almost 0.7%, while the infection rate in open surgery varies from 0.6% to 3%. Moreover, the infection can be early when it arises within 4 months of the implant or late when it arises after 4 months. Since 1991 only 94 cases of endograft infections have been reported in the world literature, to which our two cases need to be added, making a total of 96 cases. The first of our patients was diagnosed with an early infection that was successfully treated by explanting the infected graft followed by aortic reconstruction with a homograft. Six months after the operation the patient died of cardiac failure. The second case was a late infection which developed 8 years after the first intervention in a patient with chronic renal failure treated with dialytic therapy. After aneurysmectomy and stent-graft removal, a bifurcated dacron silver graft was implanted. The patient died of cardiogenic shock 40 days after surgery. The surgical treatment of this serious complication is associated with high perioperative morbidity and mortality rates and requires very careful planning of the operation.

[Treatment of the peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IHPC): postoperative morbidity and mortality and short-term follow-up]. / Trattamento della carcinosi peritoneale con chirurgia citoriduttiva e chemioipertermia intraperitoneale (IHPC): morbilità e mortalità postoperatorie e risultati a breve termine.

BACKGROUND: In order to treat the peritoneal carcinomatosis from abdominal neoplasms has been recently proposed complete peritonectomy associated with IntraPeritoneal Hyperthermic Chemotherapy (IHPC). AIM OF THE STUDY: Estimate of postoperative morbidity and mortality and short-term outcome. METHODS: Twenty-four patients with peritoneal carcinomatosis or positive cytology at peritoneal washing were treated in our Department from January 2005 to October 2007. Primary tumor was ovarian carcinoma in ten patients: four cases presented peritoneal surface malignancies (PSM) after any time from hysteroadnexectomy related to primary tumor, six cases synchronous PSM. Primary tumor was gastric cancer in seven patients: the peritoneal washing was positive in four cases and, during follow-up period after gastrectomy, other two cases presented PSM. One patient was previously treated with ovariectomy for ovaric mass that resulted a Krukenberg's tumor of gastric cancer. Primary tumor was pseudomixoma peritonei in four patients; cytoreductive surgery and IHPC was carried as first line therapy in only one patient. Three patients were previously treated for colon carcinoma. IHPC was carried out through abdominopelvic cavity for 60 minutes using a closed abdomen technique. The drugs used were Mitomycin C (3.3 mg/m2/L) and Cisplatin (25 mg/m2/L). The intracavitary mean temperature was 41.8 degrees C. RESULTS: The mean Peritoneal Cancer Index (PCI) was 14. Postoperative major complications occurred in 7 cases (28%), postoperative minor complications occurred in 8 cases (32%). No patients died in the postoperative period. Mean hospital staying was 11.5 days ( 6-35 days). After a median follow-up of 8 months (range 2-34), 14 (58%) patients are alive and 13 are disease free. CONCLUSIONS: Our experience is consistent with other studies for the high rate of postoperative morbidity associated with treatment, but we achieved best results on mortality and post-operative staying. CRS associated with IHPC is a good therapeutic option especially in ovaric-related carcinosis and PMP. It' s still debated whether it could be useful or not in colorectal related carcinosis, whereas there is a general agreement in the un uselessness of this technique in gastric cancer.

[Endovascular treatment (EVAR) in patients with abdominal aortic aneurysms and synchronous neoplasms]. / Trattamento endovascolare dei pazienti affetti da aneurisma dell'aorta addominale e neoplasia sincrona.

The association between abdominal aortic aneurysms (AAA) and cancer is becoming more and more frequent, giving rise to several questions regarding the therapeutic and surgical management strategies for both diseases. Endovascular aneurysm repair (EVAR) is the treatment of choice for complex and high-risk patients. In this study we reviewed our experience with patients concomitantly affected by any type of cancer and AAA treated by EVAR at our institution over the last six years. From April 2001 to July 2007, 497 AAA patients underwent open or endografting repair in the 1st Division of General Surgery--Service of Vascular Surgery of the University of Verona. In 53 cases (10.6%) an association with a solid neoplasm was found and 27 of these patients (50.9%) were treated by EVAR. Twenty patients underwent a two-stage approach, with EVAR performed first, while in 5 cases a one-stage approach was preferred on the basis of the general condition of the patients, the site of the tumour to be resected, the logistic possibilities and increased experience of the operators with EVAR. Two patients received chemotherapy after EVAR. There was no in-hospital mortality and four perioperative complications (14.8%) were registered. During a mean follow-up of 25.7 months (range: 2-64 months) 5 deaths occurred, 2 in the short term and 3 in the long term, none of which were related to AAA treatment. Three type-2 endoleaks occurred that sealed spontaneously and 62.9% of the treated aneurysms had a mean 20% decrease in diameter while the others presented no variations. In our experience, EVAR was a safe and effective treatment of AAA patients with concomitant malignancies with a relatively low procedure-related morbidity and no mortality. A simultaneous surgical approach can be achieved safely, performing EVAR as the first step without significant risks. Simultaneous treatment has the advantage of avoiding a second major procedure and eliminates the risk of aortic aneurysm rupture in the postoperative period or during chemotherapy in patients who are usually in poor general condition. Care must be taken with regard to the choice of the device to be used and the possible vascular complications of the visceral circulation. In our opinion, EVAR should be considered the treatment of choice in these patients, taking into account, however, that this treatment is not always feasible in all cases and that in patients with a normal life-expectancy (tumour-cured) it may not always be the right choice. Thus, a multidisciplinary approach is necessary in the individual evaluation of these challenging patients in order to make the right decisions.

Lymph node involvement in gastric cancer for different tumor sites and T stage: Italian Research Group for Gastric Cancer (IRGGC) experience.

BACKGROUND: The aim of lymphadenectomy is to clear all the metastatic nodes achieving a complete removal of the tumor; nevertheless, its role in gastric cancer has been very much debated. MATERIALS AND METHODS: The frequency of node metastasis in each lymphatic station according to the International Gastric Cancer Association, was studied in 545 patients who underwent D2 or D3 lymphadenectomy from June 1988 to December 2002. RESULTS: Upper third early cancers have shown an involvement of N2 celiac nodes in 25%. In advanced cancers, there was a high frequency of metastasis in the right gastroepiploic (from 10% in T2 to 50% in T4) and in the paraaortic nodes (26% in T2, 32% in T3, 38 % in T4). N3 left paracardial nodes involvement was observed in an important share of middle third tumors (17% in T3, 36% in T4). Splenic hilum nodes metastasis were common in T3 and T4 cancers located in the upper (39%) and middle (17%) stomach. N2 nodal involvement was frequent in lower third advanced cancers. Metastasis in M left paracardial and short gastric nodes were observed in a small percentage of cases. CONCLUSION: Given the nodal diffusion in our gastric cancer patients, extended lymphadenectomy is still a rationale to obtain radical resection.

The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients.

PURPOSE: To investigate whether the ratio between metastatic and examined lymph nodes (N ratio) is a better prognostic factor as compared with traditional staging systems in patients with gastric cancer regardless of the extension of lymph node dissection. PATIENTS & METHODS: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma at 6 Italian centers. Patients with >15 (group 1, n = 1421) and those with 25%) were determined by the best cut-off approach. RESULTS: After a median follow-up of 45.5 months (range, 4-182 months), the 5-year overall survival of N0, N1, and N2 patients of group 1 versus group 2 was 83.4% versus 74.2% (P = 0.0026), 54.3% versus 44.3% (P = 0.018), and 32.7% versus 14.7% (P = 0.004), respectively, suggesting that a low number of excised lymph nodes can lead to the understaging of patients. N ratio identified subsets of patients with significantly different survival rates within N1 and N2 stages in both groups. At multivariate analysis, the N ratio (but not N stage) was retained as an independent prognostic factor both in group 1 and group 2 (HR for N ratio 1, N ratio 2, and N ratio 3 = 1.67, 2.96, and 6.59, and 1.56, 2.68, and 4.28, respectively). In our series, the implementation of N ratio led to the identification of subgroups of patients prognostically more homogeneous than those classified by the TNM system. CONCLUSION: N ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer also in case of limited lymph node dissection. These data may represent the rational for improving the prognostic power of current UICC TNM staging system and ultimately the selection of patients who may most benefit from adjuvant treatments.

Iatrogenic axillary artery injury from humeral neck fracture repair. A rare and unusual event in which and aggressive strategy was mandatory to save a child limb.

Humeral neck fracture is rarely associated with injury of the nearby axillary artery and in the English literature only 29 such cases have been reported. An injury of the distal axillary artery secondary to reduction and fixation of a humeral neck fracture is a very rare and unusual complication, to the best of our knowledge has never been reported in literature. In this paper we report the case of entrapment of the distal axillary artery in the humerus rhyme fracture in a 9-year-old child who suffered a nighttime car-accident with her father. At admission, the child presented a left humeral neck fracture with no other lesions and no neurologic problems in her limb; peripheral pulses present in her left hand at palpation. After closed reduction and pinning of the fracture with 2 K-wires, the left upper limb became ischemic and pulseless and the child was transferred at our Institution for diagnosis and treatment. In this paper we discuss the treatment to be adopted in this very unusual situation.