Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer.

The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.

Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer.

BACKGROUND: We investigated the utility of a molecular classifier tool and genetic alterations for predicting prognosis in Japanese patients with endometrial cancer. METHODS: A total of 1029 patients with endometrial cancer from two independent cohorts were classified into four molecular subtype groups. The primary and secondary endpoints were relapse-free survival (RFS) and overall survival (OS), respectively. RESULTS: Among the 265 patients who underwent initial surgery, classified according to immunohistochemistry, patients with DNA polymerase epsilon exonuclease domain mutation had an excellent prognosis (RFS and OS), patients with no specific molecular profile (NSMP) and mismatch repair protein deficiency had an intermediate prognosis, and those with protein 53 abnormal expression (p53abn) had the worst prognosis (P < 0.001). In the NSMP group, mutant KRAS and wild-type ARID1A were associated with significantly poorer 5-year RFS (41.2%) than other genomic characteristics (P < 0.001). The distribution of the subtypes differed significantly between patients with recurrence/progression and classified by sequencing (n = 764) and patients who underwent initial surgery (P < 0.001). Among patients with recurrence/progression, 51.4% had the opportunity to receive molecular targeted therapy. CONCLUSIONS: A molecular classifier is a useful tool for determining prognosis and eligibility for molecularly targeted therapy in patients with endometrial cancer.

Utility of the revised FIGO2023 staging with molecular classification in endometrial cancer.

OBJECTIVES: Molecular classification was introduced in endometrial cancer staging following the transition of the International Federation of Gynecology and Obstetrics (FIGO) 2008 to FIGO2023. In the early stages, p53 abnormal endometrial carcinoma with myometrial involvement was upstaged to stage IICm, in addition to the downstaging of POLE mutation endometrial cancer to stage IAm. This study compared the goodness of fit and discriminatory ability of FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023m); no study has been externally validated to date. METHODS: The study included 265 patients who underwent initial surgery at the National Cancer Center Hospital between 1997 and 2019 and were pathologically diagnosed with endometrial cancer. The three classification systems were compared using Harrell's concordance index (C-index), Akaike information criterion (AIC), and time-dependent receiver operating characteristic (ROC) curves. A higher C-index score and a lower AIC value indicated a more accurate model. RESULTS: Among the three classification systems, FIGO2023m had the lowest AIC value (FIGO2023m: 455.925; FIGO2023: 459.162; FIGO2008: 457.901), highest C-index (FIGO2023m: 0.768; FIGO2023: 0.743; FIGO2008: 0.740), and superior time-dependent ROC curves within 1 year after surgical resection. In the stage IIIC, patients with p53 abnormalities had considerably lower 5-year overall survival than those with a p53 wild-type pattern (24.3% vs. 83.7%, p = 0.0005). CONCLUSIONS: FIGO2023m had the best discriminatory ability compared with FIGO2008 and FIGO2023. Even in advanced stages, p53 status was a poor prognostic factor. When feasible, molecular subtypes can be added to the staging criteria to allow better prognostic prediction in all stages.

Endometrioid Endometrial Carcinoma With NKX3.1 Expression in a Transgender Man: A Case Report.

Endometrial cancer in transgender men is rare, and its histopathologic features remain unknown. A 30-yr-old transgender man with an intrauterine tumor, an ovarian mass, and a 2-yr history of testosterone use was referred to us for treatment. The presence of the tumors was confirmed via imaging, and the intrauterine tumor was identified as an endometrial endometrioid carcinoma via endometrial biopsy. The patient underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection. Pathologic examination revealed grade 3 endometrioid endometrial carcinoma, and the synchronous endometrial and ovarian tumors were collectively characterized as primary endometrial carcinoma. Metastatic carcinomas were discovered in both ovaries and the omentum, pelvic peritoneum, and a para-aortic lymph node. On immunohistochemistry, the tumor cells diffusely expressed p53, retained expression of PTEN, ARID1A, PMS2, and MSH6, and focally expressed estrogen receptors, androgen receptors, and NKX3.1. NKX3.1 was also expressed in glandular structures within the exocervical squamous epithelium. Prostate-specific antigen and prostatic acid phosphatase were focally positive. In conclusion, we describe a transgender man with NKX3.1-expressing endometrioid endometrial carcinoma who provides valuable suggestions regarding the effects of testosterone on endometrial cancer and appropriate gynecological care for transgender men.

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma.

To identify prognostic factors in patients with grade 3 (high-grade) endometrial endometrioid carcinoma, we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. Seventy-five Japanese patients with grade 3 endometrial endometrioid carcinoma, who underwent a potentially curative resection procedure between 1997 and 2018 at the National Cancer Center Hospital, were included. We classified the patients into four risk groups of the disease based on the Proactive Molecular Risk Classifier for Endometrial Cancer. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence-free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild-type CTNNB1 (p = 0.006 and p = 0.004, respectively). Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset (p = 0.01 and p = 0.01, respectively). The tendency for recurrence-free survival in the POLE exonuclease domain mutation group was better than that in the TP53 mutation and mismatch repair-deficient groups (p = 0.08 and p = 0.07, respectively), consistent with the Proactive Molecular Risk Classifier for Endometrial Cancer risk classifier definition. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with grade 3 endometrial endometrioid carcinoma, and prognosis classification using Proactive Molecular Risk Classifier for Endometrial Cancer may help screen Japanese patients with the disease.

Gross mucinous multinodular appearance aids in the identification of ovarian metastases in low-grade appendiceal mucinous neoplasms during intraoperative consultation.

Ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMNs) show grossly abundant nodular mucous cells, with a gross mucinous multinodular appearance and a histological resemblance to primary ovarian mucinous tumors (POMTs). This study aimed to elucidate the utility of gross features including the gross mucinous multinodular appearance and available clinical information at the time of intraoperative consultation, in distinguishing the ovarian metastases of LAMNs from POMTs or the ovarian metastases of colorectal cancer (CRC). In total, 776 patients with primary ovarian tumor and 68 patients with ovarian metastases underwent intraoperative consultation during 1998-2018. Of the total cases, 4 ovarian metastases of LAMNs, 19 ovarian metastases of CRC, and 50 POMTs (36 borderline tumors and 14 carcinomas) were identified. The gross features including the gross mucinous multinodular appearance were analyzed based on the gross photographs obtained before formalin fixation and the available clinical information collected during intraoperative consultation. The analysis indicated that the ovarian metastases of LAMNs significantly presented with gross mucinous multinodular appearance (4/4 vs. 0/50, P < 0.0001), extraovarian disease (4/4 vs. 2/50, P < 0.0001), ovarian surface involvement (3/4 vs. 2/50, P = 0.0016), and abnormal appendix (4/4 vs. 0/50, P < 0.0001) as compared to POMT. Moreover, the gross mucinous multinodular appearance was a distinguishable feature between the ovarian metastases of LAMNs and ovarian metastases of CRC (4/4 vs. 0/19, P = 0.0001). Based on these results, we proposed an algorithm to diagnose ovarian tumors using the gross mucinous multinodular appearance. Thus, recognizing unique gross features including the gross mucinous multinodular appearance would be useful for both pathologists and surgeons to accurately diagnose ovarian metastases of LAMNs during intraoperative consultation.

Relationship between Energy Intake and Changes in Thigh Echo Intensity during the Acute Phase of Stroke in Older Patients with Hemiplegia.

OBJECTIVE: The aim of this study was to investigate the relationship between energy intake and changes in thigh echo intensity (TEI) during the acute phase of stroke in older patients with hemiplegia. SUBJECTS AND METHODS: Older hemiplegic inpatients with stroke were enrolled in this post hoc analysis of a prospective observational study. Patients were divided into 2 groups according to energy intake during the 7 days after admission as follows: energy sufficient (ES) and energy insufficient (EIS) groups. The outcome was the rate of changes in TEI of the paralyzed and nonparalyzed sides between admission and after 4 weeks. A decrease in skeletal muscle quality is defined as an increase in intramuscular adipose tissues, which shows as an increase in echo intensity. RESULTS: The study included 44 males and 39 females (median age 81 years). The rate of change of TEI in each group was as follows: +4.5% in the ES/paralyzed group, +6.7% in the EIS/paralyzed group, -0.9% in the ES/nonparalyzed group, and +4.4% in the EIS/nonparalyzed group. The univariate analyses showed no significant difference in the rate of change in TEI between ES and EIS groups in both paralyzed side (p = 0.190) and nonparalyzed side (p = 0.183). Multivariate analysis showed that higher energy intake was associated with a smaller increase in the rate of change in TEI on the nonparalyzed side (B = -4.115, 95% confidence interval, -7.127 to -1.103). CONCLUSIONS: Higher energy intake during 7 days after admission was associated with a smaller increase in the rate of change in TEI on the nonparalyzed side upon admission and after 4 weeks.

Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients.

OBJECTIVE: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance. METHODS: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay. RESULTS: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029). CONCLUSIONS: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.

Novel classification of ovarian metastases originating from colorectal cancer by radiological imaging and macroscopic appearance.

BACKGROUND: Diagnosis of secondary ovarian tumors originating from colorectal cancer has previously been based upon history of malignancy and radiological findings of bilateral masses with a "stained glass appearance." The purpose of this study was to perform a detailed investigation of the radiological and macroscopic features of ovarian metastases originating from colorectal cancer, which remain to be fully characterized. METHODS: Study participants were 48 consecutive patients with ovarian metastases from colorectal cancer who underwent resection of ovarian tumors at the National Cancer Center Hospital between August 1998 and January 2019. Ovarian tumors were classified into subgroups using computed tomography (CT), magnetic resonance imaging (MRI), and macroscopic appearance. RESULTS: CT/MRI findings and macroscopic appearance were classified into the following four types: type 1 (oval, homogeneous-solid) (n = 5); type 2 (heterogeneous-solid, small in size with multinodular surface) (n = 3); type 3 (solid-cystic, predominantly solid) (n = 18); and type 4 (cystic-solid, multilocular with solid components) (n = 22). Type 1 mimics Krukenberg tumors, type 2 mimics ovarian metastases from breast cancer, type 3 mimics primary ovarian endometrioid cancer, and type 4 mimics primary ovarian mucinous cancer, with a "stained glass appearance". Twenty-eight (58%) patients had bilateral metastases. Eleven patients (23%) underwent hysterectomy and/or pelvic lymph node dissection in addition to ovarian resection. CONCLUSION: We introduced a novel classification system for ovarian metastases originating from colorectal cancer, which may be beneficial for assessing ovarian metastases from colorectal cancer and avoiding unnecessary surgery due to misdiagnosis of primary ovarian tumors.

Feasibility of initial treatment in elderly patients with ovarian cancer in Japan: a retrospective study.

PURPOSE: The purpose of this study was to evaluate the real world situation and clarify the problem in initial treatment for elderly patients with ovarian cancer in Japan. METHODS: We used the ovarian cancer database, containing all patients diagnosed and treated with International Federation of Gynecology and Obstetrics Stage I-IV ovarian cancer at the National Cancer Center Hospital in Japan from June 2008 to April 2013. Patients were stratified into two groups based on age: an elderly group, aged 70 years or older, and a younger group, aged below 70 years. We retrospectively assessed the rate of receiving standard therapy, and the feasibility and safety of chemotherapy compared with younger patients. RESULTS: In total, 244 patients (elderly group, 36 patients; younger group, 208 patients) were analyzed. A significantly lower proportion of elderly patients than younger patients received standard therapy (15.7% vs. 32.5%, p = 0.026). Even for the elderly group, 95% patients underwent surgery in our institution. Conversely the rate of patients receiving nonstandard chemotherapy in the elderly group was significantly higher than in the younger group (30.5% vs. 9.6%, p = 0.01). CONCLUSIONS: This study clarified the type of treatment being performed in the field, and the proportion of elderly ovarian cancer patients receiving standard therapy compared with younger patients in Japan. In addition, the actual situation of elderly patients in Japan might be different from that in Western countries. We need to evaluate the appropriate treatment for elderly patients in Japan.

[Effects of a fall intervention program for elderly patients with dementia based on person-centered care on care staff].

AIM: This study aimed to clarify the effects of a fall prevention intervention that focused on the characteristics of falls among elderly patients with dementia and was based on person-centered care in geriatric facilities on care staff. METHODS: This study was conducted between May 2016 and January 2017, and the subjects were classified into two groups: the intervention group, consisting of members who had participated in a three-month education training program, and the control group, consisting of members who provided the usual care. The study period was nine months divided as follows: training period (three months), fall prevention practice (three months), and follow-up period (three months). The quality of care was measured using the Nursing Quality Indicator for Preventing Falls (NQIPFD), and the assessment scale of health care professionals' recognition of the successful Interdisciplinary Team Approach in Health Care Facilities for the Elderly was also used. In total, the care staff members were evaluated four times: once to obtain baseline values before training, and again after the training period, after the fall prevention practice, and after the follow-up period. The results were analyzed using an analysis of variance (fixed factors = group and time, random factor = subjects, and covariance = years of experience working at the geriatric facility and type of job). RESULTS: There were 50 care staff subjects in the intervention group and 69 people in the control group. The results of the analysis of variance indicated that there was a significant difference in the NQIPFD between baseline 68.60 (±9.09) and follow-up 70.02 (±9.88) in the intervention group. With regard to the differences by intervention, the effect size of the dementia knowledge scale scores was 0.243 higher than the others, which was significant (p<0.01). CONCLUSIONS: The results showed that the participation of care staff in a fall intervention program to support elderly patients with dementia based on person-centered care significantly improved the NQIPFD and other measured factors. These findings suggest that the program fostered positive effects among the care staff.

Development of the salt-reduction and efficacy-maintenance program in Indonesia.

We conducted a randomized, controlled trial to examine the effects of a salt-reduction and efficacy-maintenance program on the improvement and maintenance of self-care and self-efficacy in reducing the salt intake of older people with high blood pressure. A total of 51 participants with hypertension/prehypertension in Indonesia were randomly assigned to a control group or one of two intervention groups: salt-reduction training or salt-reduction and efficacy-maintenance. The salt-reduction and efficacy-maintenance group received educational training and a maintenance meeting; the participants' knowledge, attitudes, self-care practices, and self-efficacy significantly improved after training and were maintained after the maintenance meeting. Participants in the salt-reduction training group showed significant effects for the same variables; however, their food salt concentrations rebounded after the maintenance meeting. No significant improvement was found in the control group. The salt-reduction and efficacy-maintenance group participants reported positive effects of salt reduction and different practices based on who prepared their meals. The salt-reduction and efficacy-maintenance group program was effective in improving and maintaining knowledge, attitudes, and self-efficacy of salt-reduction practices and could be applied with community-dwelling older people with high blood pressure.

Wechsler Adult Intelligence Scale-III profile in the early stages of Alzheimer's disease: performance in subtests sensitive to and resistant to normal decline with ageing.

AIM: This study examined the significance of age-related subtest scores from the Japanese version of the Wechsler Adult Intelligence Scale-III in patients in the early stages of Alzheimer's disease (AD). METHODS: The subjects of this study included 58 elderly Japanese persons classified into two groups: AD group (n = 29) and control group (n = 29). These groups did not differ in age, years of education, gender ratio, Hasegawa's Dementia Scale-Revised score, or Full-Scale IQ score. No subject scored below the cut-off point on Hasegawa's Dementia Scale-Revised, a frequently used dementia screen test in Japan. RESULTS: At the index score level, General Ability Index scores were the only scores that differed significantly between the groups, with the AD group scoring significantly lower than the control group (P < 0.05, Hedges' g = 0.54). At the subtest level, information scores were the only scores that differed significantly between the groups, with the AD group significantly lower than the control group (P < 0.01, Hedges' g = 0.74). CONCLUSION: The General Ability Index is a composite score that deducts components of working memory and processing speed, which are sensitive to decline with normal ageing, from the Full-Scale IQ. It also served as a subtest measuring crystallized intelligence, especially of acquired knowledge of general and factual information. Therefore, the results of this study seem to suggest that Wechsler Adult Intelligence Scale-III profile of very early AD may be characterized by weak performance on subtests normally resistant to decline with ageing.

CD8⁺ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma.

Tumor-infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non-treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan-Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log-rank test. Patients with higher numbers of CD8(+) TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis-free period. The total number of primary TILs (CD4 plus CD8) and CD8(+) primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8(+) effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8(+) T cells producing IFN-γ in PBMC were significantly higher in patients with angiosarcoma (n = 10) compared not only with that of healthy controls (n = 20) but also patients with advanced melanoma (n = 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.

Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.

The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52-81%), followed by HRAS (7-26%), CDKN2A (21-24%), and PIK3CA (5-10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.

Laparoscopic Posterior Pelvic Exenteration with Radical Vulvectomy for Intestinal-type Vulvar Adenocarcinoma.

Vulvar intestinal adenocarcinoma is a rare malignancy. The most significant predictor of advanced vulvar cancer is achieving complete resection, although determining the optimal treatment for this rare histologic type remains uncertain. We report the case of a 63-year-old woman with a primary vulvar tumor suspected of having rectal invasion and inguinal lymph node metastases based on preoperative magnetic resonance imaging and computed tomography scans. To achieve complete resection of stage IIIC intestinal-type vulvar adenocarcinoma, we performed a laparoscopic posterior pelvic exenteration (PPE) and radical vulvectomy, along with bilateral inguinal lymph node dissection. This case report highlights the use of a novel hybrid procedure that combines laparoscopic PPE with radical vulvectomy and bilateral inguinal lymph node dissection for vulvar adenocarcinoma of the intestinal type. Laparoscopic PPE can be considered a minimally invasive approach for vulvar tumor when complete resection is achievable with an appropriate safety margin.

Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report.

Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology.

Ovarian Mesonephric-Like Adenocarcinoma With Recurrent Liver Metastases: A Case Report with Analysis of Therapeutic Molecular Targets.

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare cancer subtype. We describe a patient with ovarian MLA wherein liver metastases developed 1 month after surgery. A phenotypic analysis of the tumor was performed to identify molecular therapeutic targets. A 53-year-old woman, without any symptoms, underwent uterine cancer screening. Transvaginal ultrasonography revealed an ovarian mass, and subsequent pelvic magnetic resonance imaging showed a 13 × 10 cm multicystic ovarian lesion with a solid part. No extra ovarian lesions were observed and a staging laparotomy was performed. Pathological examination revealed an MLA of the left ovary (stage IC1). The tumor comprised tumor cells in a tubular pattern with intraluminal eosinophilic material, as well as mixed glandular and papillary, cord-like, and solid patterns. Endometriosis was also observed. Immunohistochemically, the tumor cells were positive for PAX8, GATA3 (focal), TTF1 (focal), and CD10 (luminal) and negative for the estrogen receptor, progesterone receptor, and WT1. One month after surgery, computed tomography revealed multiple liver metastases. Additional immunohistochemistry for therapeutic targets revealed that the tumor cells were weakly positive for human epidermal growth factor receptor 2 (focal; score 1+), pan-tropomyosin receptor kinase-negative, programmed death-ligand 1-negative, and PMS2 and MSH6 intact. The companion homologous recombination deficiency test (MyChoice®) showed homologous recombination repair proficiency. These findings suggest that poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors may not be effective treatment options. A literature review revealed that data on therapeutic targets in MLA are scarce. In summary, we report a patient with ovarian MLA showing an aggressive clinical course and the phenotypic analysis of the tumor may contribute to the identification of therapeutic targets for MLA.

[Survey of the preoperative smoking cessation in patients for elective surgery in a university hospital].

BACKGROUND: In 2006, we reported the smoking status of surgical patients, and the factors relating to preoperative abstinence from cigarettes. Recently implementation of smoke-free policies has increased in Japan. Therefore we performed preoperative interview of 1,124 patients scheduled for elective surgery in 2011 (during 6 months), and compared the results with those of the same interview of 1,968 patients in 2006 (during 12 months). METHODS: Anesthesiologists interviewed all patients using a standardized questionnaire regarding: medical history, smoking history, and awareness of the risks of perioperative smoking. RESULTS: Current smoking rate was not different between 2006 (7%) and 2011 (7%). It was more difficult to quit smoking preoperatively for female patients in 2011 (P = 0.030), and those with benign disease in both 2006 (P = 0.006) and 2011 (P = 0.050) [smoker vs ex-smoker (< three months)]. There was no improvement in awareness of the perioperative risk of smoking between 2006 and 2011. CONCLUSIONS: At present, the importance of perioperative smoking cessation has not been sufficiently well-known for the surgical patients. Health care workers should be more aware of the importance of informing patients that preoperative abstinence from cigarettes may decrease perioperative complications.

Reconsideration of Sharp Dissection in Gynecological Surgery.

In surgical fields, sharp dissection is a basic surgical technique, and the prognosis and oncological outcomes are known to be affected by the technique of dissection. Even in gynecologic surgery, we believe that the basic surgical technique is sharp dissection. We herein present our technique and discuss its significance. Sharp dissection should entail the removal of a single thin line between the residual tissue and the excised tissue. If this line becomes multiple or thicker, it is not sharp dissection but blunt dissection. The accumulation of this thin line of sharp dissection can form surgical layers. What is important is moderate tissue tension and how to use monopolar. One can sharply cut the loose connective tissue assisted by moderate tissue tension. With regard to the use of monopolar, it is essential that it not be applied directly to the tissue, but rather be used with or without touching the tissue. Inadvertent blunt dissection should be minimized, as most surgical procedures can be performed with sharp dissection. We usually perform sharp dissection for open surgery as well as minimally invasive surgery. We obstetricians and gynecologists should reconsider the significance of sharp dissection and practice it in gynecological surgery.