Biodegradation of non-steroidal anti-inflammatory drug loxoprofen by a hyper lignin-degrading fungus Phanerochaete sordida YK-624 under non-ligninolytic conditions.

Loxoprofen has been widely used as a non-steroidal anti-inflammatory drug globally and it can also persist in the environment. Although it is known to be a non-toxic drug, its presence may still pose a potential risk to organisms in the environment. Here, the hyper lignin-degrading fungus Phanerochaete sordida YK-624 was used to study the degradation of loxoprofen. This fungus showed excellent loxoprofen biodegradation ability with 90.4% and 93.4% after one day of incubation at lower concentrations of 0.01 and 0.005 mM, respectively. And at a higher concentration of 0.1 mM, a significant removal of 94.2% was also observed after 10 days of incubation. In this study, four metabolites were isolated and determined by HR-ESI-MS and NMR. Furthermore, LC/MS analysis suggested the presence of intermediate hydroxy loxoprofen. In addition, loxoprofen-OH was also identified as a metabolite of loxoprofen through comparison with the synthesized compounds. In this metabolism of loxoprofen, cytochrome P450 may play a significant role. Interestingly, P. sordida YK-624 showed enantioselectivity in the degradation process of loxoprofen. By these results, three degradation pathways of loxoprofen by P. sordida YK-624 were hypothesized. To the best of our knowledge, this is the first report describing the potential degradation mechanisms of loxoprofen by a white-rot fungus.

RNA-Seq analysis of the fruiting bodies and mycelia of angel-wing mushroom Pleurocybella porrigens that cause acute encephalopathy.

OBJECTIVE: In 2004, after consuming angel-wing mushrooms, Pleurocybella porrigens, 59 incidents of food poisoning were reported in Japan. Consequently, 17 individuals died of acute encephalopathy. In 2023, we proved that a lectin, pleurocybelline, and pleurocybellaziridine from this mushroom caused damage to the brains of mice. Although we reported genomic and transcriptomic data of P. porrigens in 2013, the assembly quality of the transcriptomic data was inadequate for accurate functional annotation. Thus, we obtained detailed transcriptomic data on the fruiting bodies and mycelia of this mushroom using Illumina NovaSeq 6000. RESULTS: De novo assembly data indicated that the N50 lengths for the fruiting bodies and mycelia were improved compared with those previously reported. The differential expression analysis between the fruiting bodies and the mycelia revealed that 1,937 and 1,555 genes were significantly up-regulated in the fruiting bodies and the mycelia, respectively. The biological functions of P. porrigens transcripts, including PA biosynthetic pathways, were investigated using BLAST search, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The obtained results revealed L-valine, a predicted precursor of PA, is biosynthesized in the fruiting bodies and mycelia. Furthermore, real-time RT-PCR was performed to evaluate the accuracy of the results of differential expression analysis.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Lignin-degrading enzymes from a pathogenic canker-rot fungus Inonotus obliquus strain IO-B2.

Inonotus obliquus is a pathogenic fungus found in living trees and has been widely used as a traditional medicine for cancer therapy. Although lignocellulose-degrading enzymes are involved in the early stages of host infection, the parasitic life cycle of this fungus has not been fully understood. In this study, we aimed to investigate the activities of laccase (Lac), manganese peroxidase (MnP), and lignin peroxidase (LiP) from I. obliquus cultivated in Kirk's medium. The fungus was subjected to genome sequencing, and genes related to wood degradation were identified. The draft genome sequence of this fungus comprised 21,203 predicted protein-coding genes, of which 134 were estimated to be related to wood degradation. Among these, 47 genes associated with lignin degradation were found to have the highest number of mnp genes. Furthermore, we cloned the cDNA encoding a putative MnP, referred to as IoMnP1, and characterized its molecular structure. The results show that IoMnP1 has catalytic properties analogous to MnP. Phylogenetic analysis also confirmed that IoMnP1 was closely related to the MnPs from Pyrrhoderma noxium, Fomitiporia mediterranea, and Sanghuangporus baumii, which belong to the same family of Hymenochaetaceae. From the above results, we suggest that IoMnP1 is a member of MnPs.

Heterologous expression of the lectin CmRlec from Cordyceps militaris (Cordycipitaceae, Ascomycota) in Escherichia coli.

Ascomycete lectins may play an important role in their life cycle. In this report, we mined a ricin B-type lectin, named CmRlec, from the Cordyceps militaris genome by homology search. Furthermore, we succeeded in the soluble expression of CmRlec using ß-glucuronidase as a solubilization tag and demonstrated that this lectin is a novel chitin-recognizing lectin.

Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP/-DQ on engraftment in cord blood transplantation.

BACKGROUND AIMS: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood. METHODS: We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLA-DP and -DQ on CBT outcomes. RESULTS: Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT. CONCLUSIONS: Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units.

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

CmLec4, a lectin from the fungus Cordyceps militaris, controls host infection and fruiting body formation.

Fungi belonging to the Ascomycete genus Cordyceps are endoparasitoids and parasites, mainly of insects and other arthropods. Cordyceps militaris has been used as a therapeutic drug for cancer patients. However, the infection, parasitism, and fruiting body formation mechanisms of this fungus are still unknown. Based on our hypothesis that lectin(s) is involved in the interaction between the C. militaris fungi and insects, we partially purified and characterized a new lectin from C. militaris, designated CmLec4. In addition, we searched for substance(s) in the infected silkworm extracts that could bind to CmLec4, and succeeded in purifying the sex-specific storage protein 2 as a specific binding target. To examine function of the binding protein during the process of parasitism, we investigated the effect of recombinant CmLec4 on silkworms by inoculating the protein into silkworm pupae, and found that it significantly delayed emergence compared to the control. Furthermore, cmlec4 gene knockout strains constructed in this study produced markedly lower amounts of fruiting body than the wild-type strain. All the results revealed that the lectin CmLec4 produced by C. militaris would be involved in the infection into silkworm and fruiting body formation from the host.

The complete mitochondrial genome sequence of the fairy ring-forming fungus Lepista sordida.

Lepista sordida is a fairy ring-forming fungus that belongs to the family Tricholomataceae and is widely distributed in the Northern Hemisphere. Here, we report the complete mitochondrial genome sequence of L. sordida. The mitochondrial genome (57,375 bp) contained 20 protein-coding genes, 2 ribosomal RNA genes, and 26 transfer RNA genes. Phylogenetic analysis based on 14 conserved protein sequences from L. sordida and 15 related basidiomycetes showed that L. sordida was located on the outermost branch of the Tricholomataceae clade. This study is the first to report the complete mitochondrial genome sequence of a fairy ring-forming fungus belonging to the genus Lepista.

Diagnosis and treatment of colorectal tumors: Differences between Japan and the West and future prospects.

Dye-based chromoendoscopy has long been used routinely for endoscopic diagnosis of gastrointestinal tumors including colorectal tumors in Japan. In the West, on the other hand, dye-based chromoendoscopy was not so commonly used. However, with the development of narrow band imaging (NBI), image-enhanced endoscopy diagnosis has rapidly increased in the West. The most critical difference between Japan and the West is the histopathological evaluation of the lesions, which determines a major cause of differences in diagnostic and treatment strategies. In the West, intramucosal adenocarcinoma is not diagnosed until the cancer has invaded submucosal layer. In Japan, on the other hand, cancer is mainly diagnosed based on nuclear and structural atypia, and thus intramucosal adenocarcinoma is diagnosed in lesions that correspond to high-grade adenoma in the West. In the West, since intramucosal carcinoma is not diagnosed by pathology, all benign adenomas are treated by piecemeal endoscopic resection, and only cancer invading the superficial submucosal layer is indicated for endoscopic submucosal dissection (ESD). Because of the risk of lymph node metastasis in the deep submucosal invasion, the European Society of Gastrointestinal Endoscopy and American Society for Gastrointestinal Endoscopy guidelines state that only superficial submucosal cancer is an indication for ESD. Unfortunately, it is impossible to selectively extract only superficial submucosal invasive cancer even with the use of magnified NBI and pit pattern observation. Therefore, we think that pathologists need to diagnose intramucosal adenocarcinoma with the potential to invade the submucosal layer based on the nuclear and structural atypia. Consequently, intramucosal adenocarcinoma and superficial submucosal cancers should be considered for en-bloc ESD.

Factors Associated with Polyp Detection Rate in European Colonoscopy Practice: Findings of The European Colonoscopy Quality Investigation (ECQI) Group.

Background: The European Colonoscopy Quality Investigation (ECQI) Group aims to raise awareness for improvement in colonoscopy standards across Europe. We analysed data collected on a sample of procedures conducted across Europe to evaluate the achievement of the polyp detection rate (PDR) target. We also investigated factors associated with PDR, in the hope of establishing areas that could lead to a quality improvement. Methods: 6445 form completions from 12 countries between 2 June 2016 and 30 April 2018 were considered for this analysis. We performed an exploratory analysis looking at PDR according to European Society of Gastrointestinal Endoscopy (ESGE) definition. Stepwise multivariable logistic regression analysis was conducted to determine the most influential associated factors after adjusting for the other pre-specified variables. Results: In our sample there were 3365 screening and diagnostic procedures performed in those over 50 years. The PDR was 40.5%, which is comparable with the ESGE minimum standard of 40%. The variables found to be associated with PDR were in descending order: use of high-definition equipment, body mass index (BMI), patient gender, age group, and the reason for the procedure. Use of HD equipment was associated with a significant increase in the reporting of flat lesions (14.3% vs. 5.7%, p < 0.0001) and protruded lesions (34.7% vs. 25.4%, p < 0.0001). Conclusions: On average, the sample of European practice captured by the ECQI survey meets the minimum PDR standard set by the ESGE. Our findings support the ESGE recommendation for routine use of HD colonoscopy.

Factors Associated with Withdrawal Time in European Colonoscopy Practice: Findings of the European Colonoscopy Quality Investigation (ECQI) Group.

The European Colonoscopy Quality Investigation (ECQI) Group aims to raise awareness for improvement in colonoscopy standards across Europe. We analyzed data collected on a sample of procedures conducted across Europe to evaluate the achievement of the European Society of Gastrointestinal Endoscopy (ESGE) mean withdrawal time (WT) target. We also investigated factors associated with WT, in the hope of establishing areas that could lead to a quality improvement. METHODS: 6445 form completions from 12 countries between 2 June 2016 and 30 April 2018 were considered for this analysis. We performed an exploratory analysis looking at WT according to the ESGE definition. Stepwise multivariable logistic regression analysis was conducted to determine the most influential associated factors after adjusting for the other pre-specified variables. RESULTS: In 1150 qualifying colonoscopies, the mean WT was 7.8 min. Stepwise analysis, including 587 procedures where all inputs were known, found that the variables most associated with mean WT were a previous total colonoscopy in the last five years (p = 0.0011) and the time of day the colonoscopy was performed (p = 0.0192). The main factor associated with a WT < 6 min was the time of day that a colonoscopy was performed. Use of sedation was the main factor associated with a higher proportion of WT > 10 min, along with a previous colonoscopy. CONCLUSIONS: On average, the sample of European practice captured by the ECQI survey met the minimum standard set by the ESGE. However, there was variation and potential for improvement.

Quantification of residual cryoprotectants and cytotoxicity in thawed bovine ovarian tissues after slow freezing or vitrification.

STUDY QUESTION: How much residual cryoprotectant remains in thawed/warmed ovarian tissues after slow freezing or vitrification? SUMMARY ANSWER: After thawing/warming, at least 60 min of diffusion washing in media was necessary to significantly reduce the residual cryoprotectants in ovarian tissues frozen by slow freezing or vitrification. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) by slow freezing has been the conventional method; while the vitrification method has gained popularity for its practicality. The main concern about vitrification is how much potentially toxic residual cryoprotectant remains in the warmed tissues at the time of transplantation. STUDY DESIGN, SIZE, DURATION: This was an animal study using the ovarian tissues from 20 bovine ovaries. The duration of this study was from 2018 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortex tissues were prepared from 20 bovine ovaries and assigned randomly to groups of fresh (non-frozen) control, slow freezing with 1.5 M dimethyl sulfoxide (DMSO), 1.5 M 1,2-propanediol (PROH) and vitrification with 35% ethylene glycol (EG). The residual cryoprotectant concentrations in thawed/warmed tissues were measured by gas chromatography at the following time points: frozen (before thawing/warming), 0 min (immediately after thawing/warming), 30, 60 and 120 min after diffusion washing in media. Next, the ultrastructural changes of primordial follicles, granulosa cells, organelles and stromal cells in the ovarian tissues (1 mm × 1 mm × 1 mm) were examined in fresh (non-frozen) control, slow freezing with DMSO or PROH and vitrification with EG groups. Real-time quantitative PCR was carried out to examine the expressions of poly (ADP-ribose) polymerase-1 (PARP1), a DNA damage sensor and caspase-3 (CASP3), an apoptosis precursor, in thawed/warmed ovarian tissues that were washed for either 0 or 120 min and subsequently in tissues that were ex vivo cultured for 24 or 48 h. The same set of tissues were also used to analyze the protein expressions of gamma H2A histone family member X (γH2AX) for DNA double-strand breaks and activated caspase-3 (AC3) for apoptosis by immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: The residual cryoprotectant concentrations decreased with the extension of diffusion washing time. After 60 min washing, the differences of residual cryoprotectant between DMSO, PROH and EG were negligible (P > 0.05). This washing did not affect the tissue integrity or significantly elevate the percentage of AC3 and γH2AX positive cells, indicating that tissues are safe and of good quality for transplantation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Since the study was performed with ovarian tissues from bovines, generalizability to humans may be limited. Potential changes in ovarian tissue beyond 120 min were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: This study addresses concerns about the cytotoxicity of EG in warmed ovarian tissues and could provide insights when devising a standard vitrification protocol for OTC. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science to N.S.

Colonoscopy quality across Europe: a report of the European Colonoscopy Quality Investigation (ECQI) Group.

Background and study aims The European Colonoscopy Quality Investigation (ECQI) Group comprises expert colonoscopists and investigators with the aim of raising colonoscopy standards. We assessed the levels of monitoring and achievement of European Society of Gastrointestinal Endoscopy (ESGE) performance measures (PMs) across Europe using responses to the ECQI questionnaires. Methods The questionnaire comprises three forms: institution and practitioner questionnaires are completed once; a procedure questionnaire is completed on multiple occasions for individual total colonoscopies. ESGE PMs were approximated as closely as possible from the data collected via the procedure questionnaire. Procedure data could provide rate of adequate bowel preparation, cecal intubation rate (CIR), withdrawal time, polyp detection rate (PDR), and tattooing resection sites. Results We evaluated ECQI questionnaire data collected between June 2016 and April 2018, comprising 91 practitioner and 52 institution questionnaires. A total of 6445 completed procedure forms were received. Institution and practitioner responses indicate that routine recording of PMs is not widespread: adenoma detection rate (ADR) is routinely recorded in 29 % of institutions and by 34 % of practitioners; PDR by 42 % and 47 %, CIR by 62 % and 64 %, bowel preparation quality by 56 % and 76 %, respectively. Procedure data showed a rate of adequate bowel preparation of 84.2 %, CIR 73.4 %, PDR 40.5 %, mean withdrawal time 7.8 minutes and 12.2 % of procedures with possible removal of a non-pedunculated lesion ≥ 20 mm reporting tattooing. Conclusions Our findings clearly show areas in need of quality improvement and the importance of promoting quality monitoring throughout the colonoscopy procedure.

Polyprev: Randomized, Multicenter, Controlled Trial Comparing Fecal Immunochemical Test with Endoscopic Surveillance after Advanced Adenoma Resection in Colorectal Cancer Screening Programs: A Study Protocol.

Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesion is detected, clinical practice guidelines recommend endoscopic surveillance with different intervals between explorations. Endoscopic surveillance is producing a considerable increase in the number of colonoscopies, with a limited effect on the CRC incidence. Instead, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non-inferior alternative to endoscopic surveillance to reduce 10-year CRC incidence. Based on this hypothesis, we have designed a multicenter and randomized clinical trial within the Spanish population CRC screening programs to compare FIT surveillance with endoscopic surveillance. We will include individuals aged from 50 to 65 years with complete colonoscopy and advanced lesions resected within the CRC screening programs. Patients will be randomly allocated to perform an annual FIT and colonoscopy if fecal hemoglobin concentration is ≥10 µg/g, or to perform endoscopic surveillance. On the basis of the non-superior CRC incidence, we will recruit 1894 patients in each arm. The main endpoint is 10-year CRC incidence and the secondary endpoints are diagnostic yield, participation, adverse effects, mortality and cost-effectiveness. Our results may modify the clinical practice after advanced colonic resection in CRC screening programs.

An efficient heterologous Escherichia coli-based expression system for lectin production from Pleurocybella porrigens.

In this study, we report a more efficient heterologous expression of lectin from Pleurocybella porrigens (PPL) using an Escherichia coli-based expression system. The yield (9.3 mg/L culture broth) of recombinant PPL (rPPL) using this expression system was increased approximately 9-fold compared to our previous study. The rPPL obtained in this study exhibited the same biochemical properties as the native PPL.

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan.

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20-70 years old with Stages IB1-IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians' questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients' questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4-5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients' questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

INTRODUCTION: rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. MATERIAL AND METHODS: this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.