Verrucous carcinoma of the larynx is a distinct and uncommon variant of well-differentiated squamous cell-carcinoma. The authors hybridized in situ a case of laryngeal verrucous carcinoma with DNA prebes to humman papillomavirus (HPV) 6, 11, 16, 18, 31, 33 and 35. The DNAs from the verrucous carcinoma of larynx hybridized with mixed DNA probes HPV-16/18 and 31/33/35. In addition, there was an evidence of HPV infection based on hybridization with mixed DNA probe HPV-6/11 in the adjacent papilloma tissue. By in situ DNA hybridization techniques, we clearly demonstrated human papillomavirus (HPV-16/18, and 31/33/35) related sequences in this neoplasm. These findings suggest the role of HPV-6/11 in the development of laryngeal papilloma ad HPV-16/18 and 31/33/35 probably on the progression to verrucous carcinoma.
Humans

Epidermal growth factor receptor(EGFR) mRNA was assessed in 7, 12-dimethylbenz(a) anthracene(DMBA)-induced squamous cell carcinomas(SCC) in the hamster buccal pouch model to elucidate the role and timing of histologic changes and differentiation during carcinogenesis. In situ reverse-transcriptase polymerase chain reaction was used to identify the EGFR. DMBA(0.5%) in heavy mineral oil was applied to the right buccal pouch 3 times per week for up to 16 weeks. Hyperplasia was detected by histologic analysis at 4 weeks, dysplasia with or without papillomatous changes at 8 weeks, and SCC at 16 weeks. Paraffin embedded sections of the tumors were used for EGFR mRNA and immunohistochemical determinations. EGFR cDNA was synthesized in situ by reverse transcription using an EGFR-specific oligonucleotide primer. In situ PCR amplification in the presence of digoxigenin-11-dUTP and subsequent binding with an antidigoxigenin antibody conjugated to alkaline phosphatase allowed direct visualization. EGFR mRNA was localized in the nuclei of the basal cell layer of normal squamous epithelium but is expanded to the superficial squamous cell layer as well as the basal cell layer in hyperplasia and dysplasia and is diffusely expressed in squamous cell carcinoma. EGFR protein, detected by immunostaining using a monoclonal antibody, was expressed mainly in the cytoplasm of superficial squamous cell layers(not in the basal cell layer) in normal squamous epithelium. It increased gradually in level and amount through the stages of hyperplasia and dysplasia to invasive squamous cell carcinoma. These results suggest that the biological markers EGFR mRNA and EGFR protein may be used for assessing intermediate end points in tests of various chemopreventive agents on oral carcinogenesis in the hamster buccal pouch model as well as in human clinical trials.
Alkaline Phosphatase ; Animals ; Biomarkers ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cricetinae* ; Cytoplasm ; DNA, Complementary ; Epidermal Growth Factor* ; Epithelium ; Humans ; Hyperplasia ; Mineral Oil ; Paraffin ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor* ; Reverse Transcriptase Polymerase Chain Reaction* ; Reverse Transcription ; RNA, Messenger ; RNA-Directed DNA Polymerase*

PURPOSE: To determine whether Tc-99mMIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively Tc-99mMIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular Tc-99m-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. MATERIALS AND METHODS: We measured percentage uptake of Tc-99m-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of Tc-99m-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. RESULTS: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of Tc-99m-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 degree C than 4 degree C. In the presence of verapamil, cyclosporin or dipyridamole, Tc-99m-MIBI uptake was increased upto 604% in mdr1 positive cells. CONCLUSION: Cellular uptake of Tc-99m-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest that Tc-99m-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents In vitro.
Animals ; Cell Line ; Cyclosporine ; Dipyridamole ; Doxorubicin ; Drug Resistance, Multiple* ; Leukemia L1210 ; Leukemia* ; P-Glycoprotein ; Technetium Tc 99m Sestamibi* ; Verapamil ; Vincristine

PURPOSE: The aim of this study was to determine whether crossed cerebellar hyperperfusion (CCH) was helpful in discriminating mesial from lateral temporal lobe epilepsy (TLE) and what other factors were related in the development of CCH on ictal brain SPECT. MATERALS AND METHODS: We conducted retrospective analysis in 59 patients with TLE (M:41, F:18; 27.4+/-7.8 years old; mesial TLE: 51, lateral TLE: 8), which was confirmed by invasive EEG and surgical outcome (Engel class I , II). All the patients underwent ictal Tc-99m HMPAO brain SPECT and their injection time from ictal EEG onset on video EEG monitoring ranged from 11 sec to 75 sec (32.6+/-19.5 sec) in 39 patients. Multiple factors including age, TLE subtype (mesial TLE or lateral TLE), propagation pattern (hyperperfusion localized to temporal lobes, spread to adjacent lobes or contralateral hemisphere) and injection time were evaluated for their relationship with CCH using multiple logistic regression analysis RESULTS: CCH was observed in 18 among 59 patients. CCH developed in 29% (15/51) of mesial TLE patients and 38% (3/8) of lateral TLE patients. CCH was associated with propagation pattern; no CCH (0/13) in patients with hyperperfusion localized to temporal lobe, 30% (7/23) in patients with propagation to adjacent lobes, 48% (11/23) to contralateral hemisphere. Multiple logistic regression analysis revealed that propagation pattern (p=0.01) and age (p=0.02) were related to the development of CCH. CONCLUSION: Crossed cerebellar hyperperfusio ictal brain SPECT did not help differentiate mesial from lateral temporal lobe epilepsy. Crossed cerebellar hyperperfusion was associated with propagation pattern of temporal lobe epilepsy and age.
Brain* ; Electroencephalography ; Epilepsy ; Epilepsy, Temporal Lobe* ; Humans ; Logistic Models ; Retrospective Studies ; Technetium Tc 99m Exametazime* ; Temporal Lobe* ; Tomography, Emission-Computed, Single-Photon*

BACKGROUND AND OBJECTIVES: The pathogenesis and etiology of inverted papilloma (IP) has not yet been clearly defined. The relationship between sinonasal IP and various strains of human papillomavirus (HPV) has been examined previously. Yet, there is little consensus regarding the incidence or role of HPV in IP. This study was performed to investigate the possible role of EBV in IP and to draw a relationship between histopathologic progression and EBV status. MATERIALS AND METHODS: This study is comprised of 19 cases of IP and 10 cases of turbinate mucosa as control. To find out the presence of EBV in paraffin block, we used PCR and ISH. Also, the author examined coexisting areas of dysplasia or malignant transformation and compared histologic findings with the results of molecular biologic studies. RESULTS: In PCR, the EBV genome was detected in 15 of 19 sinonasal IP (78.9%). By using ISH with the EBV oligonucleotide probe, EBV mRNA were found to be scattered throughout the epithelium in the IP with a similar incidence in PCR (13/19, 68.4.7%). One case of malignancy and all three dysplasia cases had EBV genome in PCR. In the middle turbinate mucosa which were used as control, 3/4 of the cases showed EBV genomes that are positive to PCR. CONCLUSION: The above results imply that EBV plays a role in the pathogenesis of IP and also indicate that the middle turbinate might be a site of viral persistence.
Consensus ; Epithelium ; Genome ; Herpesvirus 4, Human* ; Humans ; In Situ Hybridization* ; Incidence ; Mucous Membrane ; Papilloma, Inverted* ; Paraffin ; Polymerase Chain Reaction* ; RNA, Messenger ; Turbinates

The use of somastostatin in chyle fistula that occurs after neck dissection is a new approach that has been reported in few cases. We report two cases of chyle fistula that occurred after neck dissection, which were successfully managed with somatostatin subcutaneous injection. Somatostatin treatment resulted in an immediate reduction of chyle leakage in both patients, and might have contributed to the reduction of patients' morbidity and duration of hospital stay. However, optimal treatment regimen with somatostatin is unclear because of its limited case and various administration methods. Further studies are required to clarify the usefulness and optimal regimen of somatostatin injection in the treatment of chyle fistula following neck dissection.
Chyle ; Fistula ; Humans ; Injections, Subcutaneous ; Length of Stay ; Neck ; Neck Dissection ; Octreotide ; Somatostatin

PURPOSE: Verapamil is one of the most extensively characterized modulators of P-glyco- protein (P-gp) mediated multi-drug resistance (MDR), but its plasma concentration required to reverse MDR can cause cardiovascular toxicity. KR-30035 is a newly synthesized verapamil analogue with more potent cytostatic effects, but has lower cardiovascular effects than verapamil. We have assessed the MDR reversing effects of KR-30035 by measuring Tc-99m MIBI uptake in cultured tumor cells and in nude mice bearing human tumor xenografts. MATERIALS AND METHODS: In-vitro uptake of Tc-99m MIBI was measured in murine leukemia cells (L-1210) and those MDR-positive variants after incubation with different concentrations of KR-30035. Results were compared to those with verapamil. Organ and tumoral uptake of Tc-99m MIBI was compared between P-gp (+) human colon cancer (HCT15 cells) and P-gp (-) lung cancer (A549 cells) in nude mice, treated with either KR-30035 or verapamil. RESULTS: There was no significant difference in in-vitro uptake of Tc-99m MIBI between verapamil and KR-30035 group at any concentrations. MIBI uptake in P-gp (+) cells continuously increased either with verapamil or KR-30035 in a dose-dependent manner. Tc-99m MIBI uptake ratios of the tumor [P-gp (+' tumor uptake divided by P-gp (-) uptake] were significantly higher with KR-30035 than with verapamil in tumor bearing nude mice. Washout rate of Tc-99m MIBI from P-gp (+) HCT15 cells was lower in verapamil or KR-30035 groups than in the control group, which was 0.19, 0.19 and 0.27 respectively. CONCLUSION: These studies revealed that KR-30035 can potentially be used as an active modulator of MDR, with its significantly lesser cardiovascular toxicity than verapamil. Our results warrants further evaluation of this novel agent.
Animals ; Colonic Neoplasms ; Drug Resistance, Multiple ; Heterografts ; Humans ; Leukemia ; Lung Neoplasms ; Mice ; Mice, Nude ; P-Glycoprotein ; Plasma ; Robenidine ; Tumor Cells, Cultured ; Verapamil

BACKGROUND: With the progress of limited surgery and endoscopic treatment for early gastric cancer (EGC), multiple synchronous EGCs, a cause of recurrence, become more important. The objective of this study was to elucidate the characteristics of multiple synchronous EGCs with an emphasis on features of preoperatively undiagnosed lesions. METHODS: We retrospectively reviewed medical records of 496 patients who underwent a gastrectomy for EGC at our institution between January 2004 and December 2004. RESULTS: Twenty-four patients (4.8%) had multiple synchronous EGCs with 24 main and 27 accessory lesions. Multiple synchronous EGCs showed male predominance (p=0.03). Other characteristics including lymph node metastasis were the same as with single EGC. Out of 27 accessory lesions, six lesions (22%) were not detected preoperatively in six patients (25%). Macroscopically five lesions were flat and one lesion was depressed. Five lesions were located at the anterior or posterior wall of the middle and low third portion and one lesion was located at the lesser curvature side of the upper third portion of the stomach. Two lesions were 4 mm, one lesion was 8 mm, two lesions were 12 mm and one lesion was 15 mm in size (mean diameter = 9.1 mm). Histologically, four lesions were of the differentiated type and two lesions were of the undifferentiated type. CONCLUSIONS: Multiple synchronous EGCs have same clinicopathologic features as a single EGC except for male predominance. Considering the possibility of a synchronous lesion, one should examine the entire stomach precisely with special attention to the anterior, posterior wall and lesser curvature side of the same or neighboring area of a known EGC lesion before treatment.
Gastrectomy ; Humans ; Lymph Nodes ; Male ; Medical Records ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Stomach ; Stomach Neoplasms*

OBJECTIVE: This study assessed whether characteristics of ruptured hepatocellular carcinoma (HCC) at presentation to the emergency department (ED) affect patient outcomes, and evaluated factors prognostic of HCC, particularly treatment modalities. METHODS: This retrospective study between 2008 and 2017 evaluated patients presenting to an ED with ruptured HCC. Parameters associated with 30- and 90-day mortality were investigated, and clinical characteristics and treatments were analyzed. RESULTS: In total, 121 patients presented to the ED with ruptured HCC. Of these, 29 died within 30 days. Multivariate logistic regression analysis showed that platelet count (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.976–0.995) and prothrombin time (OR, 16.20; 95% CI, 1.91–137.23) were associated with a 30-day mortality rate, whereas presence or absence of acute abdominal pain and shock at presentation to the ED was not significant. Patients who underwent embolization had a lower 30-day mortality rate than those treated conservatively (OR, 0.04; 95% CI, 0.001-0.20). Sixtyone patients died within 90 days after presentation to the ED. Serum albumin concentration (OR, 0.25; 95% CI, 0.09–0.71) was associated with 90-day mortality. Moreover, patients who underwent embolization (OR, 0.19; 95% CI, 0.06–0.60) and emergency hepatectomy (OR 0.09; 95% CI, 0.01–0.99) had lower 90-day mortality rates as compared to patients treated conservatively. CONCLUSION Presence of acute abdominal pain at presentation to the ED does not affect patient outcomes. Early aggressive treatments, such as embolization or emergency hepatectomy, were observed to improve outcomes in patients with ruptured HCC.

The assessment of epithelial changes in gastric mucosal biopsies has been one of the major problems caused by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, members of the Study Group for Pathology of Digestive Diseases reviewed microslides of 50 gastric lesions showing varying degrees of mucosal abnormality and reached the following consensus; 1) the proliferating gastric epithelium can be divided into hyperplastic and neoplastic; 2) the term "dysplasia" is reserved for the microscopic epithelial changes that are unequivocally neoplastic; 3) Biopsy specimens can be categorized as regenerative(negative for dysplasia), indefinite(questionable dysplasia), positive(positive for dysplasia) and overt carcinoma; 4) The positive category can be divided into two subgroups, high grade dysplasia and low grade dysplasia. Criteria for each grade are presented and discussed. We offer these guidelines for establishing the correct diagnosis of the gastric mucosal biopsy specimens and for prospective studies.
Biopsy ; Consensus ; Diagnosis ; Epithelium ; Pathology*