Structured Reporting of CT Angiography Runoff Examinations of the Lower Extremities.

OBJECTIVES: The aim was to evaluate the effect of structured reporting of computed tomography angiography (CTA) runoff studies on clarity, completeness, clinical relevance, usefulness of the radiology reports, further testing, and therapy in patients with known or suspected peripheral arterial disease. METHODS: Conventional reports (CRs) and structured reports (SRs) were generated for 52 patients who had been examined with a CTA runoff examination of the lower extremities. The sample size was based on power calculations with a power of 95% and a significance level of .007 (adjusted for multiple testing). CRs were dictated in a free text form; SRs contained a consistent ordering of observations with standardised subheadings. CRs were compared with SRs. Two vascular medicine specialists and two vascular surgeons rated the reports regarding their satisfaction with clarity, completeness, clinical relevance, and usefulness as well as overall satisfaction. Additionally, they made hypothetical decisions on further testing and therapy. Median ratings were compared using the Wilcoxon signed rank test and generalised linear mixed effects models. RESULTS: SRs received higher ratings for satisfaction with clarity (median rating 9.0 vs. 7.0, p < .0001) and completeness (median rating 9.0 vs. 7.5, p < .0001) and were judged to be of greater clinical relevance (median rating 9.0 vs. 8.0, p < .0001) and usefulness (median rating 9.0 vs. 8.0, p < .0001). Overall satisfaction was also higher for SRs (median rating 9.0 vs. 7.0, p < .0001) than CRs. There were no significant differences in further testing or therapy. CONCLUSION: Referring clinicians perceive SRs of CTA runoff examinations of the lower extremities as offering superior clarity, completeness, clinical relevance, and usefulness than CRs. Structured reporting does not appear to alter further testing or therapy in patients with known or suspected peripheral arterial disease.

Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease.

BACKGROUND: Clinical decision making in abdominal aortic aneurysms (AAA) relies completely on diameter. At this point, improved decision tools remain an unmet medical need. Our goal was to identify changes at the molecular level specifically leading up to AAA rupture. METHODS AND RESULTS: Aortic wall tissue specimens were collected during open elective (eAAA; n=31) or emergency repair of ruptured AAA (rAAA; n=17), and gene expression was investigated using microarrays. Identified candidate genes were validated with quantitative real-time polymerase chain reaction in an independent sample set (eAAA: n=46; rAAA: n=18). Two gene sets were identified, 1 set containing 5 genes linked to terminal progression, that is, positively associated with progression of larger AAA, and with rupture (HILPDA, ANGPTL4, LOX, SRPX2, FCGBP), and a second set containing 5 genes exclusively upregulated in rAAA (ADAMTS9, STC1, GFPT2, GAL3ST4, CCL4L1). Genes in both sets essentially associated with processes related to impaired tissue remodeling, such as angiogenesis and adipogenesis. In gene expression experiments we were able to show that upregulated gene expression for identified candidate genes is unique for AAA. Functionally, the selected upregulated factors converge at processes coordinated by the canonical HIF-1α signaling pathway and are highly expressed in fibroblasts but not inflammatory cells of the aneurysmatic wall. Histological quantification of angiogenesis and exploration of the HIF-1α network in rAAA versus eAAA shows enhanced microvessel density but also clear activation of the HIF-1α network in rAAA. CONCLUSIONS: Our study shows a specific molecular fingerprint for terminal AAA disease. These changes appear to converge at activation of HIF-1α signaling in mesenchymal cells. Aspects of this cascade might represent targets for rupture risk assessment.

Predictive factors for better bypass patency and limb salvage after prosthetic above-knee bypass reconstruction.

BACKGROUND: Peripheral arterial disease (PAD) is one of the most underestimated diseases because of its high prevalence and unfavorable prognosis. Many PAD patients without suitable autologous veins or options for endovascular treatment receive prosthetic above-knee femoropopliteal bypass (PAKB). Until now predictors of prosthetic bypass failure and of increased amputation risk remain indistinct. This study aimed to identify predictive factors associated with better bypass patency and limb salvage to achieve a more favorable outcome after PAKB reconstruction. METHODS: Pre-, intra-, and postoperative data of 244 PAKB procedures performed at a German university medical center were collected and analyzed using univariate and multivariate methods. To our knowledge this 12-year experience is the largest retrospective study to identify predictors for patency and limb salvage after PAKB reconstruction. RESULTS: Of the PAD patients 94% (229/244) were followed for an average of 34.9 months. Patient cohorts characteristics were: mean age, 66.1 years, 181 men (74%), claudication (64%), rest pain (16%), ischemic lesions (20%), arterial hypertension (92%), smoking (79%), hyperlipidemia (65%) and type 2 diabetes (43%). Cumulative primary 1- and 3-year graft patency rates were 60.8% and 50.7%, respectively, and cumulative 1- and 3-year limb salvage rates were 89.3% and 86.1%, respectively. One hundred seven bypasses (43.9%) failed, 26 patients (10.7%) required a major and seven patients (2.9%) required a minor amputation. Overall survival rates of PAD patients after 1- and 3-years were 94.4% and 82.9%, respectively. Subjective symptom improvement was found to be the most important prognostic follow-up factor for graft patency and limb salvage. Patients with recurrent symptoms in the follow-up had an increased risk of emerging bypass failure compared with patients with subjective symptom improvement (patency at 1 year: 40.8% vs 100% and at 3 years: 26% vs 100%; P < .001). No patient with subjective improvement in symptoms during follow-up underwent an amputation (limb salvage at 1 year: 100% vs 79% and at 3 years: 100% vs 72.8%; P < .001). Therefore, subjective symptom improvement should be the decisive criterion to determine follow-up intervals of PAD patients. In univariate analysis further significant factors associated with better graft patency and limb salvage rates were: claudication compared with critical ischemia, larger graft diameter (>6 mm), pre- and postoperative antiplatelet therapy, statin therapy independent from lipid values after PAKB revascularization, and an experienced vascular surgeon. CONCLUSIONS: In our study, we determined the subjective improvement in symptoms as the most important prognostic factor for bypass function and limb salvage after PAKB. Furthermore, disease stage of critical ischemia, graft diameter, preoperative aspirin use, and postoperative statin medication were independent predictive factors. Therefore, PAD patients should be treated with aspirin pre- and postoperatively as well as with a statin postoperatively. In case of PAKB reconstruction only prostheses with a large diameter (>6 mm) should be used and the procedure should be performed by an experienced surgeon. Considering these results with regard to the predictive factors for better graft patency and limb salvage rates a significant more favorable outcome during the follow-up and an increased 5-year patency rate for PAKB reconstructions can be expected.

Smad4 loss synergizes with TGFα overexpression in promoting pancreatic metaplasia, PanIN development, and fibrosis.

AIMS: While overexpression of TGFα has been reported in human pancreatic ductal adenocarcinoma (PDAC), mice with overexpressed TGFα develop premalignant pancreatic acinar-to-ductal metaplasia (ADM) but not PDAC. TGF-ß signaling pathway is pivotal to the development of PDAC and tissue fibrosis. Here we sought to investigate the interplay between TGFα and TGF-ß signaling in pancreatic tumorigenesis and fibrosis, namely via Smad4 inactivation. METHODS: The MT-TGFα mouse was crossed with a new Smad4 conditional knock-out mouse (Smad4flox/flox;p48-Cre or S4) to generate Smad4flox/flox;MT-TGFα;p48-Cre (STP). After TGFα overexpression was induced with zinc sulfate water for eight months, the pancreata of the STP, MT-TGFα, and S4 mice were examined for tumor development and fibrotic responses. PanIN lesions and number of ducts were counted, and proliferation was measured by Ki67 immunohistochemistry (IHC). Qualitative analysis of fibrosis was analyzed by Trichrome Masson and Sirius Red staining, while vimentin was used for quantification. Expression analyses of fibrosis, pancreatitis, or desmoplasia associated markers (α-SMA, Shh, COX-2, Muc6, Col1a1, and Ctgf) were performed by IHC and/or qRT-PCR. RESULTS: Our STP mice exhibited advanced ADM, increased fibrosis, increased numbers of PanIN lesions, overexpression of chronic pancreatitis-related marker Muc6, and elevated expression of desmoplasia-associated marker Col1A1, compared to the MT-TGFα mice. The inactivation of Smad4 in the exocrine compartment was responsible for both the enhanced PanIN formation and fibrosis in the pancreas. The phenotype of the STP mice represents a transient state from ADMs to PanINs, closely mimicking the interface area seen in human chronic pancreatitis associated with PDAC. CONCLUSION: We have documented a novel mouse model, the STP mice, which displayed histologic presentations reminiscent to those of human chronic pancreatitis with signs of early tumorigenesis. The STP mice could be a suitable animal model for interrogating the transition of chronic pancreatitis to pancreatic cancer.

Perforated inferior vena cava filters as the cause of unclear abdominal pain.

Inferior vena cava filters are considered a valuable therapeutic option in patients with deep vein thrombosis, subsequent pulmonary emboli, and contraindication for anticoagulation. However, these filters bear the risk of rare but serious complications (e.g., symptomatic caval perforation). We report our experiences with retrievable vena cava filters by means of an actual case and review the recent literature with special regard to filter-dependent delayed symptomatic vena cava perforations. Here, an inferior vena cava filter could be identified as the source of a patient's abdominal pain; after an interventional retrieval approach had failed, open surgical removal became necessary and led to the instant relief of this patient's symptoms. Retrievable vena cava filter removal should be performed in all cases as soon as no longer needed to avoid fatal complications.

Antiviral re-treatment of IFN-ribavirin non-responders for recurrent post-transplantation hepatitis C.

BACKGROUND: The aim of the study was to compare the efficacy and tolerability of pegylated interferon (PEG-IFN) plus ribavirin (RIB) and PEG-IFN monotherapy after unsuccessful initial therapy with interferon-α2b (IFN) plus RIB after recurrent post-transplantation hepatitis C. METHODS: Twenty-four patients with either no response (n = 10) or relapse (n = 14) after treatment with IFN plus RIB were prospectively randomized in the two treatment arms: 1) PEG-IFN monotherapy at a dosage of 0.8 µg/kg per week (n = 12) and 2) PEG-IFN (0.8 µg/kg per week) plus RIB (800-1200 mg/d) (n = 12). RESULTS: Twenty-one patients (86%) were treated for at least six months. Three patients are still being treated. At the end of therapy, 18 patients (75%) were HCV RNA negative. Five (45%) patients in PEG-IFN and five (50%) in PEG-IFN plus RIB arms had sustained virological response. Two patients (10%) died from recurrent hepatocellular carcinoma. The histologic activity indices significantly improved in both treatment arms. In the PEG-IFN arm, one patient experienced an acute rejection and discontinued therapy. CONCLUSIONS: Both treatment arms showed to be effective, well tolerated and lead to an improvement in histologic outcome. Because of lower rates in side effects and equal outcome, PEG-IFN monotherapy is an adequate option for antiviral re-treatment.

Mutational analyses of the BRAF, KRAS, and PIK3CA genes in oral squamous cell carcinoma.

OBJECTIVES: The development of oral squamous cell carcinoma (OSCC) is a complex, multistep process. To date, numerous oncogenes and tumor-suppressor genes have been implicated in oral carcinogenesis. Of particular interest in this regard are genes involved in cell cycling and apoptosis, such BRAF, KRAS, and PIK3CA genes. STUDY DESIGN: Mutations of BRAF, KRAS, and PIK3CA were evaluated by direct genomic sequencing of exons 1 of KRAS, 11 and 15 of BRAF, and 9 and 20 of PIK3CA in OSCC specimens. RESULTS: Both BRAF and KRAS mutations were detected with a mutation frequency of 2% (1/42). PIK3CA mutations were detected at 3% (1/35). CONCLUSIONS: This is the first report implicating BRAF mutation in OSCC. Our study supports that mutations in the BRAF, KRAS, and PIK3CA genes make at least a minor contribution to OSCC tumorigenesis, and pathway-specific therapies targeting these 2 pathways should be considered for OSCC in a subset of patients with these mutations.

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.

Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been reported. However, tumor-suppressor genes that may account for the frequent LOH remain to be identified. Recently, one systematic study of genomic sequencing was performed on breast and colorectal cancers and 189 candidate cancer genes (CAN-genes) were reported. Among those CAN-genes, 13 genes are located on chromosome 3p. To investigate whether any of the 13 CAN-genes on chromosome 3p is relevant to HNSCC tumorigenesis, we examined their mutational profiles in eight HNSCC cell lines and 12 tumor-normal pairs of human HNSCC in this study. Three of the 13 CAN-genes, ALS2CL, EPHA3, and CMYA1, each was found to harbor a missense mutation (1/20, 5% for each of the three genes). The mutations appeared hemizygous and SNP array analyses showed that these missense mutations are accompanied by LOH on the remaining allele. In summary, our data offer further support that ALS2CL, EPHA3, and CMYA1 are bona-fide tumor-suppressor genes and contribute to the tumorigenesis of HNSCC. Our data suggest that multiple tumor-suppressor genes are likely to be involved in accounting for the high LOH on chromosome 3p in HNSCC.

Listeria monocytogenes as a rare cause of mycotic aortic aneurysm.

Mycotic aneurysms represent a diagnostic and therapeutic challenge still lacking general recommendations for optimal therapy. So far, Listeria monocytogenes (L. monocytogenes) is very rarely reported to be the causative organism of mycotic aortic aneurysms. We report 2 cases of mycotic abdominal aortic aneurysms due to L. monocytogenes infection being treated by radical debridement, open in situ reconstruction with aorto-bi-iliac Dacron grafts, and long-term antibiotic therapy. Both patients recovered well from surgery. Interestingly, the long-time follow-up for the first patient 9 years after surgery was entirely uneventful. Open debridement in an in situ reconstruction with Dacron grafts followed by antibiotic therapy seems to be a suitable therapeutic regime for mycotic aneurysms due to L. monocytogenes.

Molecular analysis of PIK3CA, BRAF, and RAS oncogenes in periampullary and ampullary adenomas and carcinomas.

BACKGROUND: Mutations of KRAS are known to occur in periampullary and ampullary adenomas and carcinomas. However, nothing is known about NRAS, HRAS, BRAF, and PIK3CA mutations in these tumors. While oncogenic BRAF contributes to the tumorigenesis of both pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms/carcinomas (IPMN/IPMC), PIK3CA mutations were only detected in IPMN/IPMC. This study aimed to elucidate possible roles of BRAF and PIK3CA in the development of ampullary and periampullary adenomas and carcinomas. METHODS: Mutations of BRAF, NRAS, HRAS, KRAS, and PIK3CA were evaluated in seven adenomas, seven adenomas with carcinoma in situ, and 21 adenocarcinomas of the periampullary duodenal region and the ampulla of Vater. Exons 1 of KRAS; 2 and 3 of NRAS and HRAS; 5, 11, and 15 of BRAF; and 9 and 20 of PIK3CA were examined by direct genomic sequencing. RESULTS: In total, we identified ten (28.6%) KRAS mutations in exon 1 (nine in codon 12 and one in codon 13), two missense mutations of BRAF (6%), one within exon 11 (G469A), and one V600E hot spot mutation in exon 15 of BRAF. BRAF mutations were present in two of five periampullary tumors. All mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. CONCLUSION: Our data provide evidence that oncogenic properties of KRAS and BRAF but not NRAS, HRAS, and PIK3CA contribute to the tumorigenesis of periampullary and ampullary tumors; BRAF mutations occur more frequently in periampullary than ampullary neoplasms.

Surgical treatment of mass-forming intrahepatic cholangiocarcinoma: an 11-year Western single-center experience in 107 patients.

Hepatic resection is the only cure for intrahepatic cholangiocellular carcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcome of patients with ICC. We retrospectively studied the records of 67 patients who underwent laparotomy for ICC from January 1995 through December 2005. Univariate and multivariate analyses were conducted for several variables to evaluate their influence on the outcome. Forty-five patients underwent hepatic resection. In 19 patients, the tumors were found to be unresectable at the time of laparotomy. Median 2- and 5-year survival rates in the 45 resected patients were 62% and 35%, respectively. For 36 patients who underwent curative resection, the 2- and 5-year survival were 67% and 41%, respectively; with a median survival of 43 months. The overall 5-year recurrence-free survival was 30%. The 90-day postoperative mortality rate was 4% and morbidity 28%. Multivariate analyses confirmed resection margin, lymph node involvement, blood loss, and blood transfusion to be independent significant variables for overall survival. Predictors of longer recurrence-free survival were lymph node involvement, vascular infiltration, blood loss, and transfusion. Surgical treatment of ICC by curative hepatic resection in patients without nodal invasion provides good long-term results. In contrast, incomplete tumor removal does not provide a survival benefit. An improved quality of preoperative staging was able to increase the resectability rate to acceptable 70%.

Mutational analyses of multiple oncogenic pathways in intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: There is much accumulated evidence that EGFR, HER2, and their downstream signaling pathway members such as KRAS, BRAF, and PIK3CA are strongly implicated in cancer development and progression. Recently, mutations in the kinase domains of EGFR and HER2, associated with increased sensitivity to tyrosine kinase inhibitors, have been described. METHODS: To evaluate the mutational status of these genes in intraductal papillary mucinous neoplasm (IPMN)/intraductal papillary mucinous carcinoma (IPMC), EGFR and HER2 were analyzed in 36 IPMN/IPMC, and the results were correlated to the mutational status of the KRAS, BRAF, and PIK3CA genes in the samples. RESULTS: Together, we identified 1 silent mutation of HER2, 17 (43%) KRAS mutations, 1 (2.7%) BRAF mutation, and 4 (11%) mutations of PIK3CA in the IPMN/IPMC samples. CONCLUSIONS: The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.

PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas.

BACKGROUND AND AIMS: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human tumors. Three hot-spot mutations in the exons 9 and 20 have been proven to activate the Akt signalling pathway. The Raf/MEK/ERK (mitogen-activated protein kinase) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Here we evaluate the mutational status of PIK3CA, KRAS, and BRAF in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMNC) of the pancreas. MATERIALS AND METHODS: Exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 of PIK3CA, exons 1 of KRAS, and exons 5, 11, and 15 of BRAF were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing. RESULTS: We identified four somatic missense mutations of PIK3CA within the 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported to be a hot-spot mutation. Furthermore, we found 17 (47%) KRAS mutations in exon 1 and one missense mutation (2.7%) in exon 15 of BRAF. CONCLUSION: This data is the first report of PIK3CA mutation in pancreatic cancer and it appears to be the first oncogene to be mutated in IPMN/IPMC but not in conventional ductal adenocarcinoma of the pancreas. Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

Disruption of transforming growth factor beta-Smad signaling pathway in head and neck squamous cell carcinoma as evidenced by mutations of SMAD2 and SMAD4.

The role of the TGF-beta-Smad signaling pathway in the carcinogenesis of head and neck cancer has not been fully evaluated genetically. In this study, we screened for mutation in the five main members of the TGF-beta -Smad signaling pathway, TGF-beta type I receptor (TGFBRI), TGF-beta type II receptor (TGFBRII), SMAD2, SMAD3 and SMAD4, in eight human head and neck squamous cell carcinoma (HNSCC) cell lines. Two mutations with presumed loss of heterozygosity (LOH) were identified. A novel missense mutation of SMAD2, located in exon 8 at codon 276 TCG (ser) -->TTG (leu), was identified in cell line SCC-15. This is the first report of a biallelic mutation of the SMAD2 gene in HNSCC. A nonsense mutation of the SMAD4 gene in exon 5 codon 245 CAG (glut) -->TAG (stop) was found in cell line CAL27. Western blotting verified that this nonsense mutation gives rise to the complete loss of the Smad4 protein in the cells. While the down-regulation and loss of expressions of the TGF-beta-Smad signaling pathway have been described frequently in HNSCC, here we offer further genetic evidence that the pathway is directly targeted for mutation during the HNSCC tumorigenesis.

BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.

The Raf/MEK/ERK (MAPK) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas.

PURPOSE: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human solid tumors. More than 75% of those somatic mutations are clustered in the helical (exon 9) and kinase domains (exon 20). The three hot-spot mutations, E542K, E545K, and H1047R, have been proven to elevate the lipid kinase activity of PIK3CA and activate the Akt signaling pathway. The mutational status of PIK3CA in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) has not been evaluated previously. EXPERIMENTAL DESIGN: To evaluate a possible role for PIK3CA in the tumorigenesis of IPMN and IPMC, exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing. RESULTS: We identified four missense mutations in the nine screened exons of PIK3CA from 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported as a hot-spot mutation. The remaining three mutations, T324I, W551G, and S1015F, were novel and somatic. CONCLUSION: This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/IPMC.

Collagen foil (TissuFoil E) reduces the formation of adhesions when using polypropylene mesh for the repair of experimental abdominal wall defects.

BACKGROUND AND AIMS: Polypropylene meshes (PPMs) are routinely used in the treatment of incisional hernias to achieve a tension-free closure of the abdominal wall. Severe adhesions are a common cause of intestinal obstruction, or even intestinal fistulas. Using a porcine model, we investigated whether applying a collagen foil (CF) to the undersurface of a PPM will reduce adhesion formation. METHODS: In ten domestic pigs (20-25 kg), a median laparotomy was performed. In each animal the abdominal wall was reconstructed using three types of closure: simple closure by a running suture (control), PPM only, and PPM covered with CF (PPM-CF). After 6 weeks, the abdominal wall with adherent tissue was resected en bloc for macroscopic (quality and quantity of adhesion formation) and histological work-up. RESULTS: The PPM-CF showed significantly less severe (1.9 vs 3.0 according to a scoring system), and also less extended (23.8 vs 55.9% total coverage of the mesh), adhesions to the resected abdominal wall. Histological examination revealed fewer and less severe inflammatory reactions, necrosis, and foreign body reactions for the mesh and CF (PPM-CF). CONCLUSION: To combine meshes with the anti-adhesion properties of a CF may be another option to achieve more physiological and more tolerable prosthetic materials.

PIK3CA mutations in head and neck squamous cell carcinoma.

PURPOSE: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC. EXPERIMENTAL DESIGN: More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens. RESULTS: We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A --> G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples. CONCLUSIONS: These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.