Near-infrared venous imaging may be more useful than ultrasound guidance for novices to obtain difficult peripheral venous access: A crossover simulation study.

BACKGROUND: Difficult peripheral venous access, especially in obese people, is challenging for novices. We conducted a randomized cross-over study to examine whether near-infrared venous imaging or ultrasound guidance is more useful for novice operators to obtain difficult peripheral venous access. METHODS: Medical students were recruited as participants. After receiving basic training using commercial simulators, participants were randomly assigned to obtain simulated venous access using a difficult venous access simulator with near-infrared venous imaging or ultrasound guidance in a randomized cross-over design. A difficult venous access simulator was newly developed with deep and narrow vessels to simulate an obese patient. The primary outcome measure of the study was the first-time success rate (%), and the secondary outcome measures included procedure time (seconds) and the number of 3 consecutive successful attempts, to represent proficiency with the procedure. Pearson chi-square test, the Wilcoxon signed-rank test, and generalized estimating equations were used for statistical analysis. RESULTS: Forty-one medical students with no experience performing peripheral venous access were enrolled in this study. The rate of successful first attempts did not differ between the 2 groups (70% for near-infrared; 65% for ultrasound guidance; P = .64). The duration of the procedure for the first attempt was significantly shorter using near-infrared imaging (median: 14; interquartile range: 12-19) compared to ultrasound guidance (median 46; interquartile range: 26-52; P = .007). The number of attempts until 3 consecutive successes was not significantly different comparing the 2 approaches (near-infrared: 3 (3, 7.25), ultrasound guidance: 3 (3, 6.25), P = .63). CONCLUSION: There was no difference in success rate of first-time attempts or acquiring proficiency for the 2 methods. However, duration of the first attempt was significantly shorter with near-infrared imaging than with ultrasound guidance. Near-infrared imaging may require less training than ultrasound guidance. Near-infrared venous imaging may be useful for novices to obtain difficult peripheral venous access in obese patients.

Secondary Malignant Tumors Arising in Nevus Sebaceus: Two Case Reports.

Nevus sebaceus is a benign tumor that is present at birth and is often seen on the scalp or face. Secondary malignant tumors sometimes occur in nevus sebaceus in adulthood. Herein, we present two malignant tumors arose from nevus sebaceus. One is basal cell carcinoma on the face and the other is sebaceus carcinoma on the lower back, where nevus sebaceus rarely occurs. Basal cell carcinoma sometimes develops in sebaceus nevus after a few decades, seen usually on the scalp or face. Sebaceus carcinoma is a rare malignant tumor that arises in nevus sebaceus.

Application of Immunohistochemistry in the Pathological Diagnosis of Liver Tumors.

Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation-such as hepatocyte paraffin 1 and arginase-1-and those of malignant hepatocytes-such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19. In this article, we provide an overview of the application of immunohistochemistry in the pathological diagnosis of liver tumors referring to the association with genetic alterations. Furthermore, we aimed to explain the practical points in the differential diagnosis of liver tumors by immunohistochemical staining.

The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Redox dysregulation originating from metabolic alterations in cancer cells contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. Amongst them, Vitamin K (VitK) carries the potential against cancer stem cells, in addition to the rest of tumor mass. OBJECTIVES: To assess the possible benefits and safety of VitK for cancer treatment using a systematic review and meta-analysis with a mixed-methods approach. METHODS: We performed a systematic search on several electronic databases for studies comparing VitK treatment with and without combination to the control groups. For quantitative studies, fully or partially reported clinical outcomes such as recurrence rates, survival, overall response and adverse reactions were assessed. For qualitative studies, a narrative synthesis was accomplished. RESULTS: Our analysis suggested that the clinical outcome of efficacy, the pooled hazard ratio for progression-free survival, and the pooled relative risk for overall survival, and overall response were significantly higher in the VitK therapy group compared to the placebo group (p<0.05). We did not observe any significant difference in the occurrence of adverse events between groups. Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid tumors resulted in 24.1% and 10% of clinical response, respectively. CONCLUSION: VitK not only exerts antitumor effects against a wide range of tumor types, but it also has excellent synergism with other therapeutic agents.

Differences in image-enhanced endoscopic findings between Helicobacter pylori -associated and autoimmune gastritis.

Background and study aims The aim of this study was to elucidate the differences in image-enhanced endoscopy (IEE) findings between Helicobacter - pylori -associated and autoimmune gastritis. Patients and methods Seven H. pylori -naïve, 21 patients with H. pylori -associated gastritis and seven with autoimmune gastritis were enrolled. Mucosal atrophy in the corpus was evaluated using autofluorescence imaging and classified into small, medium and large. In a 2 × 2-cm area of the lesser curvature of the lower corpus, micromucosal pattern was evaluated by magnifying narrow band imaging and proportion of foveola (FV)- and groove (GR)-type mucosa was classified into FV > 80 %, FV 50 % to 80 %, GR 50 % to 80 %, and GR > 80 %, then a biopsy specimen was taken. Results Fifteen of 21 (71 %) H. pylori -associated gastritis patients exhibited medium-to-large atrophic mucosa at the corpus lesser curvature. All autoimmune gastritis patients had large atrophic mucosa throughout the corpus ( P  < 0.001). All H. pylori -naïve patients had the FV > 80 % micromucosal pattern. Nineteen of 21 (90 %) H. pylori -associated gastritis patients had varying proportions of GR- and FV-type mucosae and five of seven (71 %) autoimmune gastritis patients showed FV > 80 % mucosa ( P  < 0.001). Compared with patients who were H. pylori -naïve, patients with H. pylori -associated and autoimmune gastritis exhibited a higher grade of atrophy ( P  < 0.001), but only patients with H. pylori -associated gastritis showed a higher grade of intestinal metaplasia ( P  = 0.022). Large mucosal atrophy with FV > 80 % micromucosal pattern had sensitivity of 71 % (95 % CI: 29 %-96 %) and specificity of 100 % (95 % CI: 88 % to 100 %) for diagnosis of autoimmune gastritis. Conclusions IEE findings of the gastric corpus differed between H. pylori -associated and autoimmune gastritis, suggesting different pathogenesis of the two diseases.

Intraoperative Diagnosis and Surgical Procedure with Imprint Cytology for Small Pulmonary Adenocarcinoma.

Objectives: For patients with multiple small-sized pulmonary cancers, a lobectomy can disrupt future therapeutic options for other lesions. It was recently reported that limited pulmonary resections were not inferior to lobectomy for the management of selected peripheral small-sized pulmonary adenocarcinomas. Patients with adenocarcinoma in situ or minimally invasive adenocarcinoma, as proposed by the International Association for the Study of Cancer classification, have been reported to have 100% survival after 5 years. However, that classification can be applied postoperatively. Since 2005, we have been intentionally performing limited pulmonary resection procedures for small-sized adenocarcinoma cases based on intraoperative imprint cytological diagnosis and our classification (Nakayama-Higashiyama's classification). Materials and Methods: A total of 120 consecutive cases were included in this study. Lung tumors were removed intraoperatively by wedge resection, and stump smear cytology was performed, from which the cases were classified into 5 groups based on our classification. When the tumor was classified as Group I or II, the operation was finished. When diagnosed as a more advanced classification, a lobectomy and lymph node dissection were additionally performed. Results: The 5-year survival rate for Group I and II was 100%, while those for Group III and IV-V were 95.8% and 94.4%, respectively. The 5-year disease-free survival rates for Group I and Group II were 100% and 97.1%, respectively, and for Group III and IV-V they were 100% and 94.1%, respectively. Conclusion: Use of cytological findings along with Nakayama-Higashiyama's classification for determining operation procedure is effective for treatment of patients with small-sized pulmonary adenocarcinoma.

Novel Imprint Cytological Classification for Small Pulmonary Adenocarcinoma Using Surgical Specimens: Comparison with the 8th Lung Cancer Staging System and Histopathological Classification.

Objectives: Small-size lung lesions suspected of being cancer are now often being identified on computed tomography. Correspondingly, a new lung cancer staging system has been proposed by the International Association for the Study of Lung Cancer (IASLC), in which the T1 factor and adenocarcinoma are re-subclassified. Previously, we proposed an intraoperative cytological diagnosis and its classification of small-size lung adenocarcinoma, which correlated significantly with clinical malignancy, to be used for selecting the surgical strategy. In the current study, the correlation of our intraoperative cytological classification with the new 8th IASLC classification was investigated. Materials and Methods: A total of 139 consecutive small-size lung adenocarcinoma cases were surgically resected from 2000 to 2006 and included in this study. Intraoperative stump imprint cytology using these specimens was performed, and the cases were classified into 5 groups based on our classification. The cytological classification was compared with the IASLC classification and the WHO histopathological grading. Results: According to our classification, 32 patients were in Group I, 38 in Group II, 24 in Group III, 27 in Group IV, and 18 in Group V. Compared with the IASLC classification, most of Group I was pTis or pT1mi, and most of Group II was pT1mi or pT1a (p<0.001). There was also a significant relationship between lymph node metastasis and our cytological classification (p<0.001). The histological patterns according to the WHO classification also had a significant relationship with our classification (p<0.001). Conclusion: Our cytological classification correlated not only with the T classification, but also with the adenocarcinoma subclassification of the 8th IASLC classification.

Preoperative Stereotactic Body Radiotherapy to Portal Vein Tumour Thrombus in Hepatocellular Carcinoma: Clinical and Pathological Analysis.

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. We conducted a prospective study to evaluate the efficacy and safety of tri-modality therapy, including preoperative stereotactic body radiotherapy (SBRT) and surgery, followed by hepatic arterial infusion chemotherapy (HAIC) in HCC patients with PVTT. In this report, we investigated the pathology of the irradiated PVTT specimen in resected cases and SBRT-related acute toxicity. A total of 8 HCC patients with PVTT received preoperative SBRT targeting the PVTT at a dose of 48 Gy in 4 fractions at our institute from 2012 to 2016. Of the eight patients, six underwent surgery, while the remaining two did not because of disease progression. At the pathological examination, all patients' irradiated PVTT specimens showed necrotic tissue, and three of six patients showed complete pathological response. Two patients showed 30% necrosis with high degeneration and one patient, with 30% necrosis without degeneration, was the only recurrent case found during the follow-up period (median: 22.5, range: 5.9-49.6 months). No SBRT-related acute toxicity worse than grade 2 was observed from SBRT to surgery. In conclusion, the preoperative SBRT for HCC was pathologically effective and the acute toxicities were tolerable.

Pathological assessment of the lymph node biopsies for lymphadenopathy in rheumatoid arthritis.

Objectives: To assess the incidence of reactive lymph node hyperplasia (RLH) and the diagnostic characteristics that can help differentiate it from lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA).Methods: Data on patient characteristic from 32 consecutive RA patients with lymphadenopathy at a single medical center over a 6-year period were collected and analyzed to determine whether any of these characteristics can differentiated RLH from LPD.Results: LPD including methotrexate (MTX) - associated LPD (MTX-LPD) and RLH were diagnosed in 19 and 10 patients, respectively. Conclusive diagnosis was not reached in the remaining three cases and they were regarded as grey-zone cases. Age, levels of lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R), as well as maximum standardized uptake value (SUVmax), were significantly higher in LPD than in RLH patients. The diagnosis cut-off values for these parameters were 66 year, 169 U/L, 899 U/mL and 8.18, respectively, based on the receiver operating characteristics curve analysis for both RLH and LPD.Conclusions: About one-third of patients with RA who presented with lymphadenopathy had reactive lymph node enlargement. Older age and higher levels of LDH, sIL-2R, and SUVmax are more associated with LPD than should be considered when deciding to perform a biopsy.

Endoscopic appearance of esophageal xanthoma.

Background and study aims Esophageal xanthomas are considered to be rare, and their endoscopic diagnosis has not been fully elucidated. The aim of the present study was to determine the characteristics of the endoscopic appearance of esophageal xanthomas. Patients and methods This was a retrospective study of consecutive patients with histologically diagnosed esophageal xanthomas at a referral cancer center in Japan. The endoscopic appearance, by magnifying or image-enhanced endoscopy, and histological findings of esophageal xanthomas were investigated. Results Seven patients (six men and one woman) were enrolled. All of the patients had a solitary lesion, and the median size was 2 mm (range, 1 - 5 mm). Conventional white-light endoscopy showed the lesions as flat areas with yellowish spots in four cases and slightly elevated yellowish lesions in three cases. Magnifying endoscopy, performed in six patients, revealed the lesions as areas with aggregated minute yellowish spots with tortuous microvessels inside. Magnifying narrow-band imaging contrasted the yellowish spots and microvessels better than white-light endoscopy. In all lesions, histological examination showed that the yellowish spots corresponded to papillae filled with foam cells. The foam cells were strongly immunopositive for CD68, and in all lesions, CD34-positive intrapapillary capillaries surrounded the aggregated foam cells. The different morphologies of the flat and slightly elevated lesions corresponded to different densities of papillae filled with foam cells. Conclusions Magnifying endoscopy revealed minute yellowish spots with tortuous microvessels inside. These correspond well with histological findings and so may be useful in the diagnosis of esophageal xanthomas.

Impact of Cumulative Smoking Exposure on Subclinical Degenerative Aortic Valve Disease in Apparently Healthy Male Workers.

BACKGROUND: Little is known regarding the impact of cumulative smoking exposure and smoking cessation on subclinical degenerative aortic valve (DAV) disease. METHODS: We examined associations of smoking status, cigarette-years of smoking, and years since quitting smoking with subclinical DAV disease defined by echocardiography. RESULTS: Of 756 apparently healthy male workers, 154 had DAV including 63 with DAV with ≥2 leaflets calcification (DAV ≥2 cal). Compared with never smokers, ever smokers had higher risk of DAV and DAV ≥2 cal; odds ratios (95% CI) were 2.883 (1.800-4.618) (p<0.001) and 5.281 (2.297-12.138) (p<0.001), respectively. Both current and former smokers had dose-dependent relationships of cigarette-years on DAV and DAV ≥2 cal (P for trend, <0.001 for both DAV, in both smokers). In current smokers with >400-≤800 and with >800 cigarette-years, odds ratios (95%CIs) were 3.201 (1.690-6.063) (p<0.001) and 5.326 (2.800-10.053) (p<0.001) for DAV, 7.460 (2.828-19.680) (p<0.001) and 8.397 (3.146-22.414) (p<0.001) for DAV ≥2 cal, respectively. In former smokers with >800 cigarette-years, odds ratios (95%CI) were 3.780 (1.970-7.254) (p<0.001) for DAV, 10.035 (3.801-26.496) (p<0.001) for DAV ≥2 cal. Compared with current smokers, former smokers with quitting smoking >10 years had significantly lower risk of DAV and DAV ≥2 cal. CONCLUSIONS: In apparently healthy male workers, DAV disease was strongly associated with smoking. Cumulative smoking exposure was associated with dose-dependent relationship on subclinical DAV disease both in current smokers and former smokers.

Performance of a new system using a one-step nucleic acid amplification assay for detecting lymph node metastases in breast cancer.

One-step nucleic acid amplification (OSNA) for CK19 mRNA is an intraoperative diagnostic procedure for detection of lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of a new OSNA system have been developed. As an improvement over a conventional system, the new system can analyze 14 samples per run, evaluate two lymph nodes in ~ 17 min, and reduce inhibition of reactions. This study was aimed at evaluating clinical performance of the new system by comparing it with performance of histopathological analysis and a conventional OSNA system. A total of 150 lymph nodes in 63 breast cancer patients (T1-3) who underwent sentinel lymph node biopsy or axillary lymph node dissection were examined intraoperatively with the new OSNA system, the conventional system, and histopathological analysis. In comparison with histopathological analysis, sensitivity, specificity, and concordance rate of the new system were 93.9, 98.8, and 96.7%, respectively. In comparison with the conventional system, similar corresponding values were obtained: 96.9, 98.8, and 98.0%, respectively. The results show that clinical performance of the new OSNA system is equivalent to that of histopathological diagnosis and the conventional OSNA system. The new system is superior to the conventional one because of processing of a greater number of samples, shorter testing time, and the absence of inhibited reactions.

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

Sporadic Minute Pharyngeal Xanthomas Detected Incidentally During Esophagogastroduodenoscopy: A Case Series.

Pharyngeal xanthomas are considered rare, and no reports have described their endoscopic appearance under magnifying or image-enhanced endoscopy. We report three cases of asymptomatic sporadic pharyngeal xanthoma that were detected incidentally during routine esophagogastroduodenoscopy. All the patients were men and had a solitary lesion of about 1 mm in size. Two of the lesions were located in the oropharynx, while one was in the hypopharynx. Non-magnifying endoscopy showed yellowish lesions, and magnifying endoscopy showed an aggregation of minute yellowish nodules with tortuous microvessels on their surface. Histopathological examination revealed foam cells filling the intraepithelial papillae. The foam cells were strongly immunopositive for cluster of differentiation (CD) 68. Immunohistochemical staining for CD34 showed intrapapillary capillaries around the foam cells. This characteristic magnifying endoscopic appearance corresponded to the histopathological findings of pharyngeal xanthomas. The present cases reveal the relationship between the endoscopic appearance and histopathological findings of pharyngeal xanthomas.

Implications of hepatic dysfunction in Kawasaki disease: Time-related changes in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and C-reactive protein levels.

IMPORTANCE: The cause of the hepatic dysfunction that commonly accompanies Kawasaki disease (KD) remains unclear. OBJECTIVE: We tried to clarify the cause of the hepatic dysfunction. METHODS: A total of 381 consecutive patients with acute KD, who had undergone inpatient treatment with intravenous immunoglobulin until the 7th day of illness, were divided into a group of 199 patients with an alanine aminotransferase (ALT) level ≥ 40 IU/L on admission (group I), a group of 52 patients with an ALT level ≥ 40 IU/L at some point after admission (group II), and a group of 130 patients with ALT levels consistently < 40 IU/L throughout hospitalization (group III). Aspartate aminotransferase (AST), ALT, total bilirubin (T-Bil), and C-reactive protein (CRP) levels were analyzed over time, and time-courses were compared. RESULTS: In the initial stage of illness, in group I, AST, ALT, T-Bil peaked on days 1-3, and AST tended to improve significantly on the 4th day (P < 0.001). T-Bil improved on day 5 (P < 0.01), and ALT improved significantly on day 6 (P < 0.001). CRP increased every day up to day 6 (P < 0.001). In group II, AST and ALT increased after admission, and thereafter CRP increased, then decreased. The frequency of use of aspirin and aspirin doses did not differ significantly in the three groups. INTERPRETATION: Recovery from liver dysfunction occurred in the initial stage of illness in group I-within the period of CRP exacerbation, which is an indicator of systemic inflammation.

Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer.

(Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue-associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

Reliability of Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Expression on Breast Cancer Cells Stored in Cellprep® Vials.

OBJECTIVE: The aim of this study was to evaluate the reliability of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) expression levels in Cellprep® (CP). STUDY DESIGN: We evaluated the stability of immunocytochemistry (ICC) of ER and HER2 for primary or recurrent breast cancer samples rinsed in CP vials. Samples were prepared from CP vials stored for 1-30 or 160-240 days. ER and HER2 statuses were determined after 1-30 days (26 and 25 tests, respectively) or 160-240 days (15 and 18 tests, respectively) with the same protocols as immunohistochemistry (IHC), and were compared with the corresponding surgically resected specimens. RESULTS: ER statuses according to CP samples showed perfect agreement (1-30 days: kappa, κ = 1; 160-240 days: κ = 1). HER2 statuses also showed good agreement (1-30 days: κ = 0.79; 160-240 days: κ = 0.64), although there were more equivocal HER2 cases in CP than in the surgically resected specimens. CONCLUSION: ER ICC in CP vials is reliable regardless of the preservation period. HER2 ICC in CP has more equivocal cases than HER2 IHC in surgically resected specimens. Both improvement of the immunostaining protocol and further validation study of in situ hybridization are indispensable for the practical application of ICC in CP.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery.

BACKGROUND/AIM: Prognostic impact of p16 expression in patients with oropharyngeal squamous cell carcinoma (OSCC) undergoing surgery is not fully examined. The aim of this study was to clarify these issues. PATIENTS AND METHODS: Sixty-four OSCC subjects were analyzed. Immuno-histochemical staining of p16, a surrogate marker for human papillomavirus (HPV), was performed histopathologically. Data were retrospectively analyzed according to p16 positivity and factors linked to prognosis were also analyzed. RESULTS: No significant difference was observed in the prognosis between the p16-positive group (n=28) and the p16-negative group (n=36). In patients undergoing post-operative radiation, the p16-positive group (n=18) had a significantly better prognosis than the p16-negative group (n=6). On multivariate analysis, transoral surgery was a significant predictor of overall survival (p=0.0173). CONCLUSION: Prognostic impact of p16 can be emphasized in a subgroup of OSCC patients undergoing surgery. Surgery with sufficient surgical margin may be chosen as the first treatment for HPV-negative OSCC in some cases.

Promotion of malignant phenotype after disruption of the three-dimensional structure of cultured spheroids from colorectal cancer.

Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell-cell contact. After the disruption, 9 spheroid lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines exhibited accelerated spheroid growth. Marker expression, spheroid forming capacity, and tumorigenesis indicated that stemness increased after spheroid disruption. In addition, the spheroid forming capacity increased in 6 of 11 spheroid lines. The disruption signature determined by gene expression profiling supported the incidence of remodeling and predicted the prognosis of patients with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increased proliferation and stemness after the disruption. Overall, the disruption and subsequent reformation of cancer spheroids promoted malignancy-related phenotypes through the activation of the WNT and ERBB pathways.