The difference in the effectiveness of human papillomavirus vaccine based on smoking status.

AIM: This study aimed to clarify (1) the effectiveness of human papillomavirus (HPV) vaccine against precancerous lesions of uterine cervical cancer and (2) the difference in these effectiveness based on smoking status. METHODS: This retrospective cross-sectional study considered women aged 20-24 who underwent cervical cancer screening in Saga City from April 2014 to March 2020. Cervical cytology and histological diagnosis were compared with or without HPV vaccination and smoking. RESULTS: The study included 7253 women (2467 vaccinated and 4786 unvaccinated). Among the vaccinated women, 462 were smokers, 2003 were nonsmokers: among the nonvaccinated women, the numbers were 1217 and 3554, respectively. 0.28% (7/2467) of participants with vaccination had HSIL+ compared to 0.77% (37/4786) without vaccination (odds ratio [OR] 0.36, 95% confidence interval [CI], 0.16-0.81). About 0.32% (8/2467) with vaccination had cervical intraepithelial neoplasia (CIN) 2+ compared to 0.69% (33/4786) without vaccination (OR 0.46, 95% CI, 0.21-1.00). Four women without vaccination had CIN3+. In nonsmokers, HPV vaccination significantly suppressed the incidence of HSIL+ from 0.42% (15/3554) to 0.1% (2/2003) (OR 0.21, 95% CI, 0.05-0.95), but the suppressive effect was not significant in smokers (OR 0.59, 95% CI, 0.22-1.56). In vaccinated women, the incidence of CIN2+ was 0.20% (4/2003) in nonsmokers and 0.87% (4/462) in smokers (OR 0.22, 95% CI, 0.05-0.89, p = 0.02). CONCLUSIONS: HPV bivalent/quadrivalent vaccination is effective in protecting against CIN but insufficient in smokers. The nine-valent vaccine should be introduced into routine vaccination as soon as possible to prevent high-risk HPV infection other than 6/11/16/18.

Development of novel deep multimodal representation learning-based model for the differentiation of liver tumors on B-mode ultrasound images.

BACKGROUND AND AIM: Recently, multimodal representation learning for images and other information such as numbers or language has gained much attention. The aim of the current study was to analyze the diagnostic performance of deep multimodal representation model-based integration of tumor image, patient background, and blood biomarkers for the differentiation of liver tumors observed using B-mode ultrasonography (US). METHOD: First, we applied supervised learning with a convolutional neural network (CNN) to 972 liver nodules in the training and development sets to develop a predictive model using segmented B-mode tumor images. Additionally, we also applied a deep multimodal representation model to integrate information about patient background or blood biomarkers to B-mode images. We then investigated the performance of the models in an independent test set of 108 liver nodules. RESULTS: Using only the segmented B-mode images, the diagnostic accuracy and area under the curve (AUC) values were 68.52% and 0.721, respectively. As the information about patient background and blood biomarkers was integrated, the diagnostic performance increased in a stepwise manner. The diagnostic accuracy and AUC value of the multimodal DL model (which integrated B-mode tumor image, patient age, sex, aspartate aminotransferase, alanine aminotransferase, platelet count, and albumin data) reached 96.30% and 0.994, respectively. CONCLUSION: Integration of patient background and blood biomarkers in addition to US image using multimodal representation learning outperformed the CNN model using US images. We expect that the deep multimodal representation model could be a feasible and acceptable tool for the definitive diagnosis of liver tumors using B-mode US.

Cytological Appearances of Ovarian Seromucinous Borderline Tumor in Ascites: Presentation of 2 Cases.

BACKGROUND: Seromucinous borderline tumor (SMBT) is a rare neoplasm which was newly defined in the 2014 WHO classification. Although the clinical and histopathological characteristics of SMBT have been well described, its cytological characteristics have not. We recently experienced 2 cases of SMBT which were defined by cytological findings of ascites. CASE PRESENTATION: Case 1 was a 65-year-old Japanese woman. Preoperative imaging studies revealed abundant ascites and a cystic tumor, with a solid component measuring 13 cm on the left ovary. Radical surgery was performed during the intraoperative diagnosis of ovarian borderline tumor, made by histological examinations of frozen tumor sections. The cytological smears of preoperatively and intraoperatively collected ascites showed many atypical cells resembling reactive mesothelial cells. Alcian-blue staining of cell block sections revealed intracytoplasmic mucin, and the results of immunohistochemistry were consistent with SMBT. The final pathological diagnosis of tumor was SMBT. Case 2 was a 28-year-old Japanese woman. Preoperative imaging studies revealed a small amount of ascites and cystic tumors with solid components in the bilateral ovaries. She initially underwent fertility preservation surgery. SMBT was suspected by cytological examination of smears of intraoperatively collected ascites and the findings of cell block. She underwent additional radical surgery based on a final pathological diagnosis of SMBT. CONCLUSION: In our experience, the tumor cells of SMBT in ascites mimicked reactive mesothelial cells. The nuclear atypia of SMBTs was intermediate between that of reactive mesothelial cells and serous carcinoma. The immunohistochemistry and mucin staining using cell block were very helpful for facilitating the cytodiagnosis of SMBT.

A Novel Non-invasive Method for Predicting Liver Fibrosis by Quantifying the Hepatic Vein Waveform.

The hepatic vein (HV) waveform by Doppler ultrasound reflects the severity of liver fibrosis. We conducted a proof-of-concept study of a new method for quantifying the HV waveform. We calculated the coefficient of variation (CV) of the HV flow velocity and created a new index "q-HV" (quantified HV) and analyzed its performance for predicting histologic liver fibrosis in 114 patients with chronic liver disease. The CV of the HV flow velocity was well associated with flattening of the waveform and the q-HV significantly increased with the progression of liver fibrosis. The areas under the curve for the prediction of fibrosis stage were 0.732 for F2, 0.772 for F3 and 0.805 for F4. Combined q-HV and FIB-4 index (widely used liver fibrosis score) increased the diagnostic accuracy for liver fibrosis. The q-HV showed good accuracy for predicting liver fibrosis; thus, q-HV is feasible and acceptable as a non-invasive tool for predicting liver fibrosis.

Significance of carcinoembryonic antigen mRNA in peritoneal lavage determined by transcription-reverse transcription concerted method in patients with low rectal cancer.

BACKGROUND/OBJECTIVE: Positive carcinoembryonic antigen (CEA) messenger RNA (mRNA) in peritoneal lavage is associated with poor prognosis in patients with colon cancer. However, there are no reports about rectal cancer. Therefore we aimed to evaluate the frequency of positive CEA mRNA in peritoneal lavage and the significance of CEA mRNA in patients with low rectal cancer. METHODS: A total of 55 patients with low rectal cancer who received curative surgical resection were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. RESULTS: Among 55 patients, 6 (10.9%) had positive CEA mRNA in peritoneal lavage. Patients with positive CEA mRNA resulted in significantly higher recurrence rate than those with negative CEA mRNA (p=0.007). Similarly, the local recurrence rate was significantly higher in the positive CEA mRNA group than in the negative CEA mRNA group (p=0.0009). Lymph node metastasis and positive CEA mRNA were independent risk factors for overall and local recurrence. CONCLUSION: Positive CEA mRNA in low rectal cancer is a factor that predisposes patients to a high risk for overall recurrence, especially for local recurrence.

Peritoneal Lavage CEA mRNA Levels Predict Conversion Gastrectomy Outcomes after Induction Chemotherapy with Intraperitoneal Paclitaxel in Gastric Cancer Patients with Peritoneal Metastasis.

BACKGROUND: The outcome of gastric cancer patients with peritoneal metastasis remains poor. We treated these patients with intraperitoneal and intravenous paclitaxel plus oral S-1 (tegafur/gimeracil/oteracil), followed by gastrectomy in responders. We evaluated the clinical significance of peritoneal lavage carcinoembryonic antigen (CEA) messenger RNA (mRNA) levels as a biomarker for indication of conversion gastrectomy. METHODS: The peritoneal lavage of 68 patients who received the above regimen as induction chemotherapy was repeatedly collected via intraperitoneal access ports. Gastrectomy was considered when improvement of peritoneal metastasis was confirmed by a second laparoscopic examination with negative peritoneal cytology. CEA and porphobilinogen deaminase mRNAs were chronologically quantified using the transcription reverse-transcription concerted reaction method. The CEA mRNA index (CmRI) was calculated as CEA mRNA/porphobilinogen deaminase mRNA × 10,000. RESULTS: Thirty-nine patients underwent gastrectomy and 29 patients did not (median survival time, 27.8 vs. 10.7 months, respectively; P < 0.001). In gastrectomy-positive patients, the outcome largely differed according to CmRI values immediately prior to surgery. Patients with a preoperative CmRI value <100 (n = 20) were associated with a significantly longer survival than those with a preoperative CmRI value >100 (n = 19) (41.8 vs. 20.1 months, respectively; P < 0.001). A preoperative CmRI value <100 was confirmed as an independent predictor of survival for gastrectomy-positive patients in the multivariate analysis. CONCLUSIONS: The CmRI reflects the response of peritoneal metastases to induction intraperitoneal chemotherapy. It may be a useful biomarker for indicating gastrectomy in gastric cancer patients with peritoneal metastasis.

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-ß-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.

Detection of carcinoembryonic antigen mRNA in peritoneal lavage by the transcription-reverse transcription concerted method indicates poor prognosis in patients with stage II and III colon cancer.

BACKGROUND: Peritoneal dissemination and positive peritoneal lavage cytology are associated with poor prognosis in colorectal cancer. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) is often used as a marker to detect micrometastases. We aimed to evaluate the prognostic significance of CEA mRNA in the peritoneal lavage of colon cancer patients. METHODS: Colon cancer patients (n = 201) who underwent curative operative resection between August 2009 and February 2013 were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. RESULTS: Positive CEA mRNA in peritoneal lavage was an independent risk factor for overall recurrence-free survival in colon cancer (P < .0001). Positive CEA mRNA was a risk factor for poorer overall recurrence in stage II and III patients (P = .04 and P = .02, respectively). Moreover, among stage III patients with positive CEA mRNA, the postoperative chemotherapy group had significantly lower overall and peritoneal recurrence rates than the no postoperative chemotherapy group (P = .001). CONCLUSION: Positive CEA mRNA in peritoneal lavage was associated with high overall recurrence rates in stage II and III colon cancer. Further study is necessary to determinate the efficacy of aggressive postoperative chemotherapy for stage II and III colon cancer patients with positive CEA mRNA.

The relationship between mismatch negativity and arousal level. Can mismatch negativity be an index for evaluating the arousal level in infants?

BACKGROUND: Electrophysiological and behavioral studies have shown that stimulus relevance contributes to auditory processing in sleep and auditory stimuli changes the sleep stages. So we observed changes in auditory processing due to sleep stages by recording infant mismatch negativity (MMN) during different states and investigated the arousal mechanisms. METHODS: Auditory event-related potentials (ERPs) of 26 neonates were recorded using high-density EGI EEG system. Stimuli consisted of 1000 Hz tones with 90% probability as standard and 1200 Hz with 10% probability as deviant. Study 1 was designed for the confirmation of the recording of MMN from neonates and Study 2 for investigating whether an appropriate stimulus onset asynchrony (SOA) of the stimulus would induce a clear difference in the latency or amplitude. RESULTS: (Study 1) MMN were obtained from all subjects. No differences of the latencies, amplitudes and distribution due to arousal or sleep stage were observed. After the MMN response occurred, a prominent negativity like Nc was seen in response to deviant stimuli in active sleep and waking state. (Study 2) No distinct differences between the difference states were seen in any SOA. CONCLUSIONS: Only MMN did not characterize the arousal or sleep stage. But the modality of the auditory evoked potentials (AEPs) may differ according to the state, so further detailed investigation could enable the detection of the infants' state using the AEP.