Epigenetic alteration: new insights moving from tissue to plasma - the example of PCDH10 promoter methylation in colorectal cancer.

BACKGROUND: Tumour-released DNA in blood represents a promising biomarker for cancer detection. Although epigenetic alterations such as aberrant promoter methylation represent an appealing perspective, the discordance existing between frequencies of alterations found in DNA extracted from tumour tissue and cell-free DNA (cfDNA) has challenged their practical clinical application. With the aim to explain this bias of agreement, we investigated whether protocadherin 10 (PCDH10) promoter methylation in tissue was associated with methylation pattern in matched cfDNA isolated from plasma of patients with colorectal cancer (CRC), and whether the strength of concordance may depend on levels of cfDNA, integrity index, as well as on different clinical-pathological features. METHODS: A quantitative methylation-specific PCR was used to analyse a selected CpG site in the PCDH10 promoter of 67 tumour tissues, paired normal mucosae, and matched plasma samples. The cfDNA integrity index and cfDNA concentration were assessed using a real-time PCR assay. RESULTS: The PCDH10 promoter methylation was detected in 63 out of 67 (94.0%) surgically resected colorectal tumours and in 42 out of 67 (62.7%) plasma samples. The median methylation rate in tumour tissues and plasma samples was 43.5% (6.3-97.8%) and 5.9% (0-80.9%), respectively. There was a significant correlation between PCDH10 methylation in cfDNA and tumour tissue in patients with early CRC (P<0.0001). The ratio between plasma and tissue methylation rate increases with increasing cfDNA integrity index in early-stage cancers (P=0.0299) and with absolute cfDNA concentration in advanced cancers (P=0.0234). CONCLUSION: Our findings provide new insight into biological aspects modulating the concordance between tissues and plasma methylation profiles.

Role of robotic surgery in colorectal resections for cancer.

In recent years, robotic surgery is becoming a valid alternative in colorectal diseases treatment to laparoscopic and traditional open surgery. The most relevant reported technical advantages of the robotic surgery are 3D-view, tremor-filtering, seven degree-free motion and a higher comfortable setting for the surgeon. Both case series and comparative studies available in Literature report only short and mid-term outcomes. These studies are able to demonstrate that robotic surgery is as safe and feasible as laparoscopic surgery regarding perioperative outcomes. Trials with long term follow up are needed to establish the real safety and effectiveness of the robotic surgery especially concerning resections for cancer. The robotic surgery could be considered a promising surgical field. The high costs represent one of the most relevant drawbacks.

One stage or two stage treatment of colorectal cancer associated to abdominal aortic aneurysm: morbidity and mortality.

The coexistence of colorectal cancer and abdominal aortic aneurysm has been observed with increasing frequency, raising several questions about therapeutic and surgical strategies for management of both diseases. This study has reviewed 440 cases (359 cases analyzed) of colorectal cancer associated with abdominal aortic aneurysm recovered in the literature from year 1987 to 2010. In 120 cases, patients were treated in one stage; in 239 cases, they were treated in two stages. The treatment in two stages was associated with a morbidity of 26.4%, with a mortality of 5% and prosthetic infection of 0.8%. The treatment in one stage had rates of complications and mortality of 13.3% and 4.2% respectively and no cases of prosthetic infection. Analysis of the literature shows that the treatment in two stages exposes patients to a higher risk of complications and prosthetic infection.

Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci.

BACKGROUND: Tumour regression grade (TRG) is used to evaluate responses to induction therapy in cancer of the oesophagus or cardia. This study aimed to determine whether inclusion of node category could improve the prognostic accuracy provided by TRG, and explore the prognostic value of an alternative classification based on size of residual foci and node category. METHODS: Patients with oesophageal or cardia cancer treated with neoadjuvant chemoradiotherapy followed by resection were studied. Treatment-induced response at the primary site was evaluated by TRG and by a method whereby patients were classified as having no residual cancer, minimal residual disease (MRD) or as non-responders. RESULTS: Between 2000 and 2007, 108 patients underwent resection. Disease-related survival decreased with increasing TRG in node-negative (N0) patients (P < 0.001), whereas in node-positive (N+) patients it was poor irrespective of TRG (P = 0.241). For N0 disease, 3-year survival in patients with MRD (58 (95 per cent confidence interval 26 to 80) per cent) was intermediate between that in patients with no residual cancer (85 (70 to 93) per cent) and non-responders (28 (4 to 59) per cent). Worst prognosis was for N+ disease (21 (9 to 36) per cent). CONCLUSION: Node category should be considered when evaluating response to induction therapy in oesophageal or cardia cancer. A new classification based on size of residual foci and node category seems promising.

Early laparoendoscopic rendezvous for acute biliary pancreatitis: preliminary results.

INTRODUCTION: Early restored patency of the papilla has been hypothesized to reduce complications and mortality of acute biliary pancreatitis. The aim of this study was to evaluate the role of urgent laparoscopic cholecystectomy with intraoperative cholangiography and rendezvous when necessary in acute biliary pancreatitis natural history. PATIENTS AND METHODS: Patients observed in the early stage of an acute biliary pancreatitis were included in the study. Operative risk assessment based on American Society of Anesthesiologists (ASA) score allowed the performance of urgent laparoscopic cholecystectomy within 72 h from onset of symptoms in 55 patients and a delayed intervention during the same admission in 21 patients. Intraoperative cholangiography was performed in all cases, and clearance of common bile duct was performed by flushing when possible, or rendezvous when necessary. Evolution of pancreatitis was evaluated with clinical and radiological monitoring. RESULTS: Urgent laparoscopic cholecystectomy was performed in all cases without conversion. At intraoperative cholangiography common bile duct was free in 25 patients, a papillary spasm was observed in 9, and common bile duct stones in 21 patients. Patency of the papilla was restored by flushing in 13 patients, while a rendezvous was necessary in 17 patients. The rate of organ failure and pancreatic necrosis was 1.8%, overall mortality was 1.8%, and overall morbidity 21.8%. No infectious complications of peripancreatic collections were observed. CONCLUSION: Urgent laparoscopic cholecystectomy with selective intraoperative rendezvous may be considered as a treatment option in the early stage of acute biliary pancreatitis.

[Endoscopic diverticulostomy for Zenker's diverticulum. Experience on 123 cases]. / Diverticulostomia endoscopica per diverticolo di Zenker. Esperienza su 123 casi.

AIM: To evaluate the short-term clinical outcome of the patients with Zenker 's diverticulum undergone to endoscopic esophago-diverticulostomy according to Collard. PATIENTS AND METHODS: A retrospective analysis evaluated 123 patients. The most common symptom was dysphagia, severe in 50 patients (40.6%) and moderate in 73 (59.4%), with a mean dysphagia score of 2.3 (range 0-4). Regurgitation was present in 70 cases (56.9%), with a mean score of 0.8 (range 0-2). The mean diameter of diverticula was 4.1 cm (range 2.5-10). The procedure was undertaken in 87 male and 36 female with a mean follow-up of 69.1 months (range 1-168). RESULTS: Good results were obtained in 82 patients (66.7%), and the improvement of symptoms in 24 (19.5%), data confirmed by pre versus postoperative dysphagia mean score (2.3 vs 0.4) and by regurgitation score (0.8 vs 0.2). The failures have been seen in 17 patients (13.8%). The mean time of the intervention was 18 minutes (range 15-40), while the mean length of postoperative hospital stay was 2.5 days (range 1-5), with a oral intake in first postoperative day (mean). Major complications were documented in 2 patients (1.6%), minor ones in 10 patients (6.1%), without mortality. CONCLUSION: Nowadays esophago-diverticulostomy according to Collard, based on our results and on the literature data, represent the most effective and safe technique for the patients with Zenker's diverticulum, with low rate of morbidity and mortality compared to the others surgical on endoscopic procedures.

Treatment of abdominal aortic aneurysms associated with pancreatic tumors: personal experience and review of the literature (1967-2006).

The aim of the present study was to discuss the approach to a rare, but challenging, clinical situation: the coexistence of an abdominal aortic aneurysm (AAA) and a pancreatic tumor. The authors present their experience and a review of the literature of the last 40 years. From January 1988 to December 2006 the authors faced 3 cases of associated AAA and pancreatic neoplasia. Through a Medline search the authors found 15 cases of this comorbidity reported in the literature from 1967 to 2006, obtaining a total number of 18 cases. The treatment of the two diseases was in a single stage in 4 cases (22%) and in two stages in 5 cases (28%), while only one pathology was treated in 7 cases (39%) and no treatment at all was attempted in 2 cases (11%). Mortality was 0%, while morbidity was 22%, i.e. in 4 cases out of 18, although no aortic prosthesis infection was recorded. From literature analysis and their experience the authors concluded that the surgical strategy in cases of AAA and a pancreatic tumor is to be chosen depending on the pancreatic tumor prognosis, the AAA dimensions and the schedule of chemotherapy. According to the authors, AAA surgical repair is recommended in case of pancreatic cystic adenoma and neuroendocrine neoplasia, in view of their good prognosis, while endovascular repair (EVAR), when feasible, is better in patients with pancreatic adenocarcinoma.

[Perianal Paget's disease: five cases report]. / Malattia di Paget perianale: presentazione di 5 casi.

AIM: Extramammary Paget's disease is a rare neoplastic condition, often associated with a synchronous or metachronous underlying skin or visceral malignancies. The aim of this study was to evaluate retrospectively the results we got in 5 cases of perianal Paget's disease and to revise what literature have reported about this issue. PATIENTS AND METHODS: Five patients with perianal EMPD were consecutively treated in our Division between March 1996 and December 2006. In 3 cases the disease was limited to the epidermidis, in one case with multiple recurrences there was dermal infiltration, and one patient had a low rectal adenocarcinoma with pagetoid phenomenon. The surgical treatment we performed in all patients was a wide perianal excision, followed by reconstruction with cutaneous grafts; the resection of rectal adenocarcinoma was carried out using the transanal approach. In two cases we performed a temporary stoma with the sigmoid colon to help the wound healing. RESULTS: We didn't record any complication neither postoperative nor at long time. Two patients developed a local recurrence, but none of our patients showed distant metastases. Four patients are alive and free from disease and one, who developed a multiple local recurrences, died for heart failure. DISCUSSION: The studies available in literature clearly distinguish between a primary EMPD (intraepidermal/intradermal) and secondary disease which is associated with anorectal adenocarcinomas and is thought to be a pagetoid phenomenon, while few informations can derive from those cases in which the disease is associated with an underlying cutaneous adnexal carcinoma. Disease tend to relapse even after a radical surgery and can have metastatic spread, also in intraepidermal form. CONCLUSIONS: Perianal EMPD is a complex disease, difficult to recognize and the association with synchronous or metachronous malignancies imposes long term clinical and instrumental follow up.

Reference miRNAs for colorectal cancer: analysis and verification of current data.

MicroRNAs (miRNAs) hold great promise in cancer research. The use of appropriate reference miRNAs for normalization of qPCR data is crucial for accurate expression analysis. We present here analysis and verification of current data, proposing a workflow strategy for identification of reference miRNAs in colorectal cancer (CRC). We performed a systematic review of studies aimed to identify stable reference miRNAs in CRC through high-throughput screening. Among the candidate miRNAs selected from the literature we excluded those predicted to target oncogenes or tumor suppressor gene. We then assessed the expression levels of the remaining candidates in exosomes, plasma and tissue samples from CRC patients and healthy controls. The expression stability was evaluated by box-plot, ∆Cq analysis, NormFinder and BestKeeper statistical algorithms. The effects of normalisers on the relative quantification of the oncogenic miR-1290 was also assessed. Our results consistently showed that different combinations of miR-520d, miR-1228 and miR-345 provided the most stably expressed reference miRNAs in the three biological matrices. We identified suitable reference miRNAs for future miRNA expression studies in exosomes plasma and tissues CRC samples. We also provided a novel conceptual framework that overcome the need of performing ex novo identification of suitable reference genes in single experimental systems.

Laparoscopic hepatic resection.

BACKGROUND: Although laparoscopy in general surgery is increasingly being performed, only recently has liver surgery been performed with laparoscopy. We critically review our experience with laparoscopic liver resections. METHODS: From January 2000 to April 2004, we performed laparoscopic hepatic resection in 16 patients with 18 hepatic lesions. Nine lesions were benign in seven patients (five hydatid cysts, three hemangiomas, and one simple cyst), five were malignant in five patients (five hepatocarcinoma), and four patients had an uncertain preoperative diagnosis (one suspected hemangioma and three suspected adenomas). The mean lesion size was 5.2 cm (range, 1-12). Twelve lesions were located in the left lobe, three were in segment VI, one was in segment V, one was in segment IV, and one was in the subcapsular part of segment VIII. RESULTS: The conversion rate was 6.2%; intraoperative bleeding requiring blood transfusions occurred in two patients. Mean operative time was 120 min. Mean hospital stay was 4 days (range, 2-7). There were no major postoperative complications and no mortality. CONCLUSIONS: Hepatic resection with laparoscopy is feasible in malignant and benign hepatic lesions located in the left lobe and anterior inferior right lobe segments (IV, V, and VI). Results are similar to those of the open surgical technique in carefully selected cases, although studies with large numbers of patients are necessary to drawn definite conclusions.

Management of distal rectal cancer: results from a national survey.

Owing to the complexity of distal rectal cancer its management requires a multidisciplinary approach. The diagnosis and the response after neoadjuvant chemoradiotherapy are not easy to assess and therefore the surgical approach is heterogeneous. The purpose of this survey is to evaluate the experiences of members of the Italian Society of Surgery in diagnosis and treatment strategies for rectal cancer and compare it with international practice. A questionnaire was devised comprising 18 questions with 11 sub-items making a total of 29 questions and submitted online to all the 2,500 members of the SIC starting from July 2010. The survey was completed in June 2011. The overall response rate was 17.8 % (444). The majority of the Italian surgeons' responses were in line with the international consensus reflecting the complex management of distal rectal cancer. Other opinions, especially those on staging, diverge from the common view of MRI being the gold standard in the assessment of loco-regional diffusion of the disease and on the superiority of FDG PET-CT versus CT for systemic staging. The timing for the re-staging and for surgery following neoadjuvant chemoradiotherapy does not reflect the international opinion. Italian surgeons are also exposed to the common difficulties encountered internationally in the management of distal rectal cancer. Probably, the implementation of an Italian rectal cancer registry and of many national and international multicentre studies may improve the management of rectal cancer in Italy.

Morphogenetic events in the perinodal connective tissue in a metastatic cancer model.

BACKGROUND: The modifications of connective tissue surrounding metastatic lymph nodes in a murine model of rectal cancer are described. METHODS: Athymic nude mice (n=36) were inoculated with 10×10(5) ht-29 cancer cells into the submucosal layer of the rectum. Control mice (n=5) were treated with a sterile buffer. Tumor and the involved lymph nodes were visualized in vivo by magnetic resonance imaging at 1 to 4 weeks after cell injection. After the sacrifice, the excised samples were processed for histology. RESULTS: After one week from cell injection all treated animals developed rectal cancer. Since the first week, neoplastic cells were visible in the nodes. In the surrounding connective tissue, the diameter of the adipocytes was reduced and a mesenchymal-like pattern with stellate cells embedded in an oedematous environment was visible. Since the second week, in the perinodal connective an enlargement of the stroma was present. The tissue was organized in cords and areas with extracellular accumulation of lipids were found. At the fourth week, we observed an enlargement of multilocular areas and lobules of elongated elements almost devoid of lipid droplets. In control animals, in absence of neoplastic masses, pelvic nodes were surrounded by a typical connective tissue characterized by unilocular adipocytes with groups of multilocular adipocytes. CONCLUSIONS: We have developed a model of rectal cancer with nodal metastases. Using this model, the work demonstrates that around secondary lesions, the morphogenetic events follow a standard evolution characterized by an early phase with lipolysis and mesenchymalization and later phases with a brown-like phenotype acquisition.

Shape and volume of internal anal sphincter showed by three-dimensional anorectal ultrasonography.

PURPOSE: The aim of this work is to characterize the shape and the volume of the internal anal sphincter (IAS) in normal subjects by three-dimensional anorectal ultrasonography. METHODS: Thirty-nine normal volunteer males (mean age 58.5 ± 18.7) and 25 females (mean age 59.4 ± 14.1) were submitted to anorectal ultrasonography. The tissue is defined by a semiautomatic procedure. Measurements of thickness, length and volume were assessed automatically. The software provides an average number of 57,600 thickness measurements, 360 length measurements for each zone (90 for each quadrant) and seven volume measurements (one for each anatomical area).The mean values of magnitudes were calculated for the entire volume in each quadrant and zone. Age and gender-related variations were analyzed. RESULTS: In assessments of the whole tissue, only thickness was gender-related, with greater thickness for females (male thickness: 1.81 ± 0.47 mm, female thickness 2.16 ± 0.57 mm, P-value<0.01).In the distal zone: thickness, length and volume were all larger in females (for male and female respectively: 1.83 ± 0.49 mm vs 2.34 ± 0.58 mm, P-value<0.01, for the thickness; 10.87 ± 2.10mm vs 12.18 ± 2.21 mm, P-value<0.02 for the length and 1501 ± 605 mm(3) vs 2169 ± 871 mm(3), P-value<0.01 for the volume). In the medial zone, only thickness was gender-related, with greater thickness in females (male thickness: 2.04 ± 0.60mm, female thickness:2.44 ± 0.74 mm, P-value<0.02).The only variation observed in the proximal zone concerned length, larger in males (respectively: 11.27 ± 2.84 mm vs 9.55 ± 2.43 mm, P-value<0.02). The male population was significantly positively correlated with ageing for volume in the whole tissue (ρ = 0.32, P-value<0.05), and for both thickness and volume in the medial zone (ρ = 0.33, P-value<0.05 for thickness; ρ = 0.39, P-value<0.02 for the volume). CONCLUSION: This new method is useful to understand both functional anal disorders and local damage which may affect only part of the muscle tissue.

A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers.

OBJECT: The work is aimed to develop a murine model of rectal cancer, which could be used to monitor lymph node metastasis development by magnetic resonance imaging (MRI) and optical imaging (OI) techniques. SUBJECTS AND METHODS: Ht-29 cancer cells were directly injected into the submucosal layer of the rectum of athymic nude mice using trans-anal rectal cancer cell injection (TARCI). Thirty-six mice were inoculated with 10×10(5) cells and five mice were treated with sterile phosphate buffer solution. One to 4 weeks after cell injection, tumor growth was evaluated in vivo using T2-weighted MRI at 4.7T. A further group of animal (n=6) treated with ht-29_luc cells, with the same protocol, was monitored by optical imaging. In both groups, the presence of the primary tumor and of lymph nodes metastasis was confirmed by histology. RESULTS: In all animals, primary tumors were detectable by MRI, 1 week from TARCI. After 4 weeks primary tumors showed a mean longitudinal diameter of about 2cm. All animals developed regional lymph node metastases. Others organs (e.g. lung or liver) were not affected. In fat-suppressed, T2-weighted MRI, lymph nodes appeared as small areas characterized by hyper-intense signal compared to muscle. OI permitted evaluation of the primary tumor growth in perineal region. CONCLUSIONS: TARCI of ht-29 cells into the rectum of nude mice is a feasible way to obtain a easily reproducible model of regional lymph node metastases could be monitored by magnetic resonance and optical imaging techniques.

The trochanteric fat pad.

Technological developments based on the use of autologous white adipose tissue (WAT) attracted attention to minor fat depots as possible sources of adipose tissue. In plastic surgery, the trochanteric fatty pad is one of the most used WAT depots for its location and organoleptic characteristics that make it particularly suitable for reconstructive procedures. Despite its wide use in clinic, the structure of this depot has never been studied in detail and it is not known if structural differences exist among trochanteric fat and other subcutaneous WAT depots. The present study was performed on trochanteric fat pad with the aim to clarify the morphology of its adipocytes, stroma and microcirculation, with particular reference to the stem niches. Histological and ultrastructural studies showed that the main peculiar feature of the trochanteric fat concerns its stromal component, which appears less dense than in the other subcutaneous WATs studied. The intra-parenchymal collagen stroma is poor and the extracellular compartment shows large spaces, filled with electron-light material, in which isolated collagen bundles are present. The adipocytes are wrapped in weak and easily detachable collagen baskets. These connective sheaths are very thin compared to the sheaths in other subcutaneous WAT depots. The capillaries are covered by large, long and thin elements surrounded by an external lamina; these perivascular cells are poor in organelles and mainly contain poly-ribosomes. In conclusion, when compared to other WAT deposits, the trochanteric fatty pad shows structural peculiarities in its stroma and microcirculation suggesting a high regenerative potential. Resistance, dissociability, microvascular weft and high regenerative potential make the trochanteric fatty pad a privileged source for harvesting in autologous WAT-based regenerative procedures.

Validation of the new AJCC TNM staging system for gastric cancer in a large cohort of patients (n = 2,155): focus on the T category.

BACKGROUND: The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system. METHODS: We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006. RESULTS: Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient's age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively). CONCLUSIONS: Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer.

New method for internal anal sphincter measurements: feasibility study.

PURPOSE: The aim of this paper is to provide a method for measuring the internal anal sphincter on the basis of the quantitative analysis of three-dimensional endosonographic images. A software calculates a large set of measurements which are able to describe the three-dimensional shape of the muscle. METHODS: A software provides four types of measurements: thickness, length, area and volume. The different magnitudes are estimated using the same reference system. The measurements obtained are modeled by functions that describe their spatial trend. The precision and reproducibility of the method was tested on a phantom before a study was performed on fifteen healthy patients. The measurements were carried out by two different operators. The inter-observer variability were assessed. RESULTS: In the phantom measurements the mean errors and the standard deviation were: 0.05 +/- 0.1 mm for the thickness, 0.02 +/- 0.12 mm for the length, -4.43 +/- 2.4 mm(2) for the area, -20.69 +/- 20.83 mm(3) for the volume. The maximum absolute differences between the measurements carried out by the two operators was: 0.18 mm for the thickness (in the 95% of the case), 1.69 mm(2) for the area (in the 95% of the case), and 0.25 mm for the length, and 29.46 mm(3) for the volume. The human IAS assessments were evaluated on each segment. The mean of the all tissue measurements carried out were (mean +/- SD): 1.71 +/- 0.34 mm for the thickness, 33.24 +/- 6.10 mm for the length, 111.28 +/- 29.08 mm(2) for the area. The mean of the volume measurements of the entire tissue was: 4124 +/- 1160 mm(3). Inter-observer variability was observed only in the anterior proximal segment for the thickness measurements by Wilcoxon's signed rank test (P value = 0.048) and for the volume assessments by the limits of agreement method (-118 to 78 mm(3)). The mean percentage errors and the limit of agreement for the measurements of the entire tissue were: 0.27 and (-0.11 to 0.12 mm) for the thickness, -2.32 and (-3.88 to 2.33 mm) for the length, -0.05 and (-9.71 to 9.83 mm(2)) for the area, -1.89 and (-366 to 240 mm(3)) for the volume. CONCLUSION: The assessments of accuracy and precision of the method result satisfactory for all four type of measurements. The reproducibility analysis confirms very good inter-observer agreement for the phantom measurements and for the most part of the IAS segments evaluations. Inter-observer variability was seen only for the thickness and volume measurements of the anterior-proximal segment. Our method provides a high number of measurements with good accuracy enabling a very detailed study of IAS morphology.

Focal C4d staining in peritubular capillaries and kidney graft survival: results of a retrospective study.

A diffuse positivity (>or=50%) of C4d in kidney graft peritubular capillaries (PTC) significantly correlates with the presence of acute or chronic antibody-mediated rejection. In contrast, significance of a "focal" deposit (10%-50%) is not yet completely defined. The purpose of this study was to assess the impact of focal positive C4d staining on graft survival. We retrospectively reviewed 63 renal biopsies in 54 kidney transplant recipients. They were performed between January 2005 and December 2008 because of graft impairement, namely, a significant increase in serum creatinine and/or urinary protein. C4d positivity was assessed by immunohistochemistry on paraffin-embedded sections, in combination with conventional histopathologic evaluation. Biopsies were classified as negative (<10%) versus with focal (10%-50%) or diffuse deposits (>50%). Cumulative survival was calculated by the Kaplan-Meier method, and Cox regression analysis was used for the multivariate analysis. Focal C4d staining in PTC significantly correlated with worse graft survival (P = .006), similarly to diffuse C4d staining. On multivariate analysis, focal C4d staining prognostically correlated with graft survival, but not recipient or donor age, prior transplantation, number of HLA mismatches or the presence of tubulitis in the sample. Focal C4d staining was associated with worse graft survival.

Software for hepatic vessel classification: feasibility study for virtual surgery.

PURPOSE: The detection and classification of hepatic vessels in diagnostic images are essential for hepatic pre-surgery planning. Our team has developed a tool for classification, analysis, and 3D reconstruction of the hepatic and portal systems. METHODS: Our software first extracts a graphic representation of a set of connected voxels, representing both systems. It then calculates two binary volumes representing the main part of the two venous systems. Finally, it combines these results to obtain the correct vessel classification. RESULTS: Segmentation steps are semi-automatic and require about 40 min to complete. Schematization and classification steps are automatic and require about 17 min for results. CONCLUSION: The software provides a correct and detailed reconstruction even where pathologies have caused morphological and geometrical variations in the vessels. The time required for the entire procedure is compatible with clinical requirements, providing an efficient tool for diagnosis and surgical planning.