SMARCA4-deficient undifferentiated cervical carcinoma is an extremely rare and aggressive malignancy, and effective treatment options are lacking. We experienced a rare case involving a patient with SMARCA4-deficient undifferentiated cervical carcinoma who was successfully managed in the long term. A woman in her 40s presented with a chief complaint of abnormal vaginal bleeding. A cervical biopsy revealed adenocarcinoma; thus, radical hysterectomy was performed with R0 tumour resection. Histopathological examination of the resected tumour showed rhabdoid features under (H&E) staining and negativity for SMARCA4 under immunohistochemical staining. Given the poor prognosis associated with SMARCA4-deficient carcinoma, adjuvant radiotherapy was added. Follow-up for more than a year revealed no evidence of recurrence. For undifferentiated cervical carcinoma with rhabdoid features on H&E staining, SMARCA4 immunostaining may be considered for risk classification and recurrence prevention. R0 resection and postoperative adjuvant radiotherapy may contribute to a good prognosis for patients with SMARCA4-deficient carcinoma.

Background:Optimal timing for treatment initiation in Mycobacterium avium complex pulmonary disease (MAC-PD) remains unclear due to lack of established rules for predicting treatment response. Methods:A retrospective observational study was conducted to develop a prediction model for treatment failure at 2 Japanese university hospitals between 2012 and 2023. Participants were 135 patients with MAC-PD who received macrolides and ethambutol-containing regimens over 1 year. Treatment failure was defined as nonachievement culture conversion at 1 year. We selected model components as cavity (categorized by diameter) and bronchiectasis (categorized by modified Reiff score) on pretreatment computed tomography. Their combinations of each category were scored based on number of lobes involved and compared by average areas under the curve calculated using k-fold cross-validation. Results:Forty-three (31.9%) of the 135 patients failed in treatment. Number of lobes with cavities > 2cm or bronchiectasis with varicose or cystic changes was designated as the prediction model, with an average area under the curve of 0.798, and was named the Bronchiectasis and Cavity Distribution score. The representative metrics were sensitivity of 0.907 at the cutoff of 2 and specificity of 0.913 at the cutoff of 4 points. The patients were stratified into low-risk (0-1 points), intermediate-risk (2-3 points), and high-risk (4-6 points) groups. The treatment failure rates were 8.0%, 35.6%, and 69.2% in the respective groups. Conclusions:With simple assessment of computed tomography findings, the Bronchiectasis and Cavity Distribution score predicted treatment failure. Although validation studies are warranted, this score may provide guidance for treatment of MAC-PD.

Obstructive sleep apnea syndrome (OSAS) is characterized by cycles of decreased blood oxygen saturation followed by reoxygenation due to transient apnea. Cognitive dysfunction is a complication of OSAS, but its mechanisms remain unclear. Eight-week-old C57BL/6J mice were exposed to intermittent hypoxia (IH) to model OSAS, and cognitive function and hippocampal gene expression were analyzed. Three groups were maintained for 28 days: an IH group (oxygen alternating between 10 and 21% in 2 min cycles, 8 h/day), sustained hypoxia group (SH) (10% oxygen, 8 h/day), and control group (21% oxygen). Behavioral tests and RNA sequencing (RNA-seq) analysis were performed. While Y-maze test results showed no differences, the IH group demonstrated impaired memory and learning in passive avoidance tests compared to control and SH groups. RNA-seq revealed coordinated suppression of mitochondrial function genes and oxidative stress response pathways, specifically in the IH group. RT-qPCR showed decreased Lars2, Hmcn1, and Vstm2l expression in the IH group. Pathway analysis showed the suppression of the KEAP1-NFE2L2 antioxidant pathway in the IH group vs. the SH group. Our findings demonstrate that IH induces cognitive dysfunction through suppression of the KEAP1-NFE2L2 antioxidant pathway and downregulation of mitochondrial genes (Lars2, Vstm2l), leading to oxidative stress and mitochondrial dysfunction. These findings advance our understanding of the molecular basis underlying OSAS-related cognitive impairment.

The clinical outcomes of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely influenced by nutritional status. However, specific nutritional intervention strategies for NTM-PD have not been established, making management challenging. This narrative review summarizes the immunopathology associated with mycobacterial infection and the effects of malnutrition on immune responses. It further examines the clinical impact of malnutrition and the nutritional characteristics of patients with NTM-PD, highlighting the significance of nutritional intervention. Additionally, we review the current knowledge on nutritional therapy for NTM-PD, drawing insights from approaches used in related conditions. Although nutritional support may improve patient outcomes and is clearly needed, evidence regarding its effectiveness remains limited. Consequently, incorporating nutritional assessment and individualized intervention into comprehensive care currently represents the best clinical practice.

Uterine myomas can cause infertility. Studies are attempting to determine the indications for myomectomy. However, the multiplicity and localization of myomas complicate this issue. We aimed to develop a visualization tool to aid patients with infertility in their decision-making for myomectomy. We included 191 women with uterine myoma attending an outpatient infertility clinic, of whom 124 patients underwent myomectomy. Of these, 65 (52.4%) patients became pregnant within 17.6 months after surgery, and 54 (83.1%) of them had a live birth. A logistic regression model predicting the pregnancy rate (area under the curve, 0.82; 95% confidence interval, 0.74-0.89; validation value, 74.6%) was generated using the leave-one-out cross-validation method. This model incorporated five factors: age, maximum level of infertility intervention following myomectomy, presence of submucosal myoma, maximum diameter of the myoma, and type of myomas (multiple or single). We successfully visualized the degree of involvement of each factor in the pregnancy rate by developing a nomogram based on this model. We expanded the data from the preoperative magnetic resonance images and applied machine learning using a convolutional neural network. The classification accuracy was 71.4% for sensitivity and 77.7% for specificity. Heatmap images, generated using gradient-weighted class activation mapping to show the classification results of this model, could distinguish between myomas that required enucleation and those that did not. Although a larger sample size is needed to further validate our findings, this innovative pilot study demonstrates the potential of machine learning to refine assessment criteria and improve patient decision-making.

Drainage of subdiaphragmatic abscesses is difficult due to its anatomical location and it can result in adverse events, including organ damage and the spread of infection. In recent years, endoscopic ultrasonography (EUS) guided drainage for upper abdominal abscesses has become available. We report a case of successful infection control using this procedure for a subdiaphragmatic cyst secondary to perforation of the sigmoid colon after cytoreductive surgery for advanced ovarian cancer. A Japanese woman in her 60s underwent laparotomy for ovarian cancer, and then developed sigmoid colon perforation 6 days after surgery. The emergency reoperation was performed, and a cyst suspected to be an antibiotic-resistant fungal abscess appeared under the left diaphragm in the postoperative period. We adopted an EUS-guided route for diagnostic and therapeutic drainage method, which enabled shrinkage of the cyst and did not concur further adverse events. This procedure was effective as a minimally invasive drainage route for subdiaphragmatic cysts.

Background:The emergence of the Omicron variant of severe acute respiratory syndrome coronavirus-2 has significantly altered the clinical features and severity of coronavirus disease 2019 (COVID-19). Objective:This study aims to evaluate whether the clinical factors that previously predicted COVID-19 remain valid following the emergence of the Omicron variant. Methods:This cross-sectional study was conducted at Showa University Fujigaoka Hospital from April 2022 to March 2023. A total of 576 patients with suspected COVID-19 were included, of which 258 (44.8%) were diagnosed with COVID-19 based on real-time reverse-transcription polymerase chain reaction tests. Clinical data were collected retrospectively, and multivariate logistic regression was used to analyze factors associated with a COVID-19 diagnosis. Results:Of the 258 patients diagnosed with COVID-19, 60% had mild disease, and the overall severity was lower than in previous reports prior to the emergence of the Omicron variant. In the multivariate analysis, only C-reactive protein (CRP) levels were significantly associated with COVID-19 (odds ratio, 0.3164; 95% confidence interval, 0.2077-0.4819), while factors such as age, sex, body mass index, lactate dehydrogenase, and comorbidities were not significantly associated. Non-COVID-19 cases were primarily bacterial infections, accounting for 57.2% of the non-COVID-19 diagnoses. Mortality rates did not differ significantly between the COVID-19 and non-COVID-19 groups. Conclusion:The clinical characteristics of COVID-19 have become less distinct since the emergence of the Omicron variant, with CRP being the primary marker associated with a COVID-19 diagnosis. As COVID-19 continues to transition towards a more common infectious disease, distinguishing it will become increasingly challenging.

Background:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), immediately became a pandemic. Therefore, nosocomial infection control is necessary to screen for patients with possible COVID-19. Objective:This study aimed to investigate commonly measured clinical variables to predict COVID-19. Methods:This cross-sectional study enrolled 1087 patients in the isolation ward of a university hospital. Conferences were organized to differentiate COVID-19 from non-COVID-19 cases, and multiple nucleic acid tests were mandatory when COVID-19 could not be excluded. Multivariate logistic regression models were employed to determine the clinical factors associated with COVID-19 at the time of hospitalization. Results:Overall, 352 (32.4%) patients were diagnosed with COVID-19. The majority of the non-COVID-19 cases were predominantly caused by bacterial infections. Multivariate analysis indicated that COVID-19 was significantly associated with age, sex, body mass index, lactate dehydrogenase, C-reactive protein, and malignancy. Conclusion:Some clinical factors are useful to predict patients with COVID-19 among those with symptoms similar to COVID-19. This study suggests that at least two real-time reverse-transcription polymerase chain reactions of SARS-CoV-2 are recommended to exclude COVID-19.

Port-site metastasis (PSM) is specific and challenging complication that occurs after laparoscopic surgery for malignant tumor. Few cases of isolated PSM in patients with early-stage endometrial cancer have been reported; the management and prognosis in this patient population is poorly understood.

Vaginoscopy has been mainly used diagnostically due to the lack of adequate equipment for performing complicated surgeries (Johary et al., 2015). However, herein, we report therapeutic vaginal endoscopic surgery (pneumovaginoscopy) for secondary malignant vaginal tumors using the vNOTES technique and devices (Kita et al., 2021, Yokoe et al., 2022). To our knowledge, this report and surgical video demonstrate the first case of successful fertility-sparing R0 tumor resection of a rare primary cervical clear cell adenocarcinoma using pneumovaginoscopy. A 12-year-old girl was referred to our outpatient clinic with a chief complaint of a genital tumor and possible clear cell carcinoma on biopsy. There was no history of diethylstilbestrol exposure. MRI and CT images suggested a polypoid cervical tumor without metastatic lesions. Therefore, we performed therapeutic pneumovaginoscopic surgery with diagnostic laparoscopy and hysteroscopy. The cervical tumor was resected completely, and hysteroscopy and laparoscopy revealed no abnormalities. The total surgical time was 123 min, and the blood loss volume was minimal. R0 resection was achieved microscopically. Postoperatively, we performed a partial cervical resection around the first surgical scar to confirm no residual tumor. There were no postoperative complications, and a 2-year follow-up revealed no recurrence. The standard treatment for early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. However, fertility-sparing minimally invasive surgery has recently been introduced for clear cell adenocarcinoma of the cervix (Su et al., 2020). Our report supports the possibility of this minimally invasive surgery under exceptional conditions. This study was approved by the ethics committee of Kansai Medical University. Written and signed informed consent was obtained from the patient's legal guardian.

OBJECTIVE:This study evaluated the feasibility and outcomes of pneumovaginoscopy-assisted radical hysterectomy (PVRH) for cervical cancer up to stage IIA using a bidirectional fascia-oriented and nerve-sparing surgical approach.METHODS:This retrospective observational cohort study examined the operative outcomes and prognoses of patients who underwent PVRH (n=59) for up to stage IIA cervical cancer. The basic procedure was Kyoto B2 (Viper Type II nerve-sparing) radical hysterectomy and pelvic lymphadenectomy through simultaneous vaginal and abdominal (open or laparoscopic) approaches. In all cases, pneumovaginoscopy (PV) was used to create a vaginal cuff and dissect the paracolpium and paracervical endopelvic fascia to minimize nerve damage.RESULTS:Thirty-eight (64.4%) patients had stage IB1 cancer. Seven (11.9%) had vaginal invasion (stage IIA1, n=4; IIA2, n=3). The abdominal approach was open in 38 cases and laparoscopic in 21. Adjuvant therapy was administered to 24 patients (41%); one patient received concurrent chemoradiotherapy for gastric-type adenocarcinoma. There were three (6.1%) intraoperative complications (CO2 gas embolism [n=1], sigmoid colon musculosa injury [n=1], and ureteral injury [n=1]) and 8 (14%) postoperative complications (lymphedema with cellulitis [n=4], vaginal cuff dehiscence [n=1], sub-ileus [n=1], symptomatic lymphocyst [n=l], and ureterovaginal fistula [n=1]). The median urination recovery period was 3 days. Microscopic R0 was achieved in all cases. The median follow-up was 44.5 (2-122) months, and no recurrence occurred.CONCLUSION:PVRH is a new fascia-oriented and nerve-sparing surgery for early-stage cervical cancer. Further, it has favorable operative outcomes and good prognoses, similar to those of adjacent pelvic surgery such as trans-anal total mesorectal excision and radical prostatectomy.

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients.

A woman in her 50s presented with lower abdominal pain. She had a diagnosis of multiple uterine myomas 3 years earlier, followed by menopause. CT showed a pelvic mass of 19.5×9.4×10.2 cm in size, containing a haemorrhagic component. It was assumed that the tumour was the previously diagnosed myoma, and that it had increased to 150% of the size noted 3 years ago. An emergent hysterectomy was performed, and the pathological diagnosis was a uterine leiomyoma, with no components suggestive of sarcoma or degeneration. We witnessed a rare case of acute abdomen caused by internodular bleeding of multiple myomas. We assumed that the source of bleeding was the vessels of the myoma pseudocapsule. These cases may be more likely to occur in patients with multiple myomas presenting around the commencement of menopause. For symptomatic relief, emergent hysterectomy is considered to be the best treatment.

Adjuvant chemotherapy combined with bevacizumab, an angiogenesis inhibitor, can improve the survival of advanced epithelial ovarian cancer (EOC), but relapse during bevacizumab maintenance therapy may occur. Despite poly adenosine ribose-polymerase (PARP) inhibitors were shown to achieve remission in the relapsed patients upon salvage chemotherapy and long-term maintenance, there is little evidence on their efficacy or criteria for selecting bevacizumab-resistant recurrent EOC patients who would benefit from PARP inhibitors. In this single-center, retrospective, case-series study, we evaluated the efficacy, safety and selection criteria for salvage chemotherapy followed by PARP inhibitors in bevacizumab-resistant EOC patients who recurred during bevacizumab maintenance. The primary endpoint was post-progression survival (PPS), and the secondary endpoints were progression-free survival (PFS) and safety. In all, the data of 49 EOC patients, most of whom were graded as stage III (91.8%) with high-grade serous histology (81.6%), were assessed. They were classified into three groups based on platinum-free interval (PFI) and response to salvage chemotherapy: platinum-based chemotherapy followed by PARP inhibitors, platinum-based chemotherapy followed by non-PARP inhibitors, and non-platinum-based chemotherapy. Survival analysis showed the median PFS and median PPS for the platinum-based chemotherapy followed by PARP inhibitors group were 326 and 771 days, which were significantly longer than the other groups. The highly platinum-sensitive relapse (PSR) group (PFI >12 months) achieved prolonged PPS, while there was no relationship between the clinical status on salvage chemotherapy and response to PARP inhibitors. Adverse events during PARP inhibitor led to withdrawal and dose reduction in >40% of patients; however, no patients discontinued the drugs. Altogether, the study results showed that maintenance therapy using PARP inhibitor was effective and feasible for patients selected based on platinum sensitivity from bevacizumab-resistant relapsed EOC. PFI after adjuvant chemotherapy could predict bevacizumab-resistant EOC patients’ response to PARP inhibitors, which might be effective despite therapeutically insufficient salvage chemotherapy.

Vaginal stump recurrence post-hysterectomy for gynecologic malignancies occurs in 2%-3% of cases. Local excision has been recognized as the primary treatment of localized recurrence, in which precise surgical margin is critical. However, R0 resection is not always easy, given the deep and narrow operation field, as well as severe postoperative fibrosis or adhesion of the vaginal stump at times. Here, we report four cases of vaginal stump recurrence of gynecologic malignancies resected by bi-directional (laparoscopic and pneumovaginoscopic) endoscopy to overcome these difficulties. The primary tumors were uterine cancer in two cases and uterine cervical and ovarian cancer in one case each. The mean operating time was 199 (162-235) minutes, blood loss was minimal, and no perioperative complications were observed. Postoperative follow-up (7.0-19.4 months) revealed no recurrence. This combined procedure could be a therapeutic option for localized vaginal stump recurrence.

Introduction: and importance: Postpartum retroperitoneal hematomas are a potential complication of childbirth. The management of secondary infections of such hematomas has not been fully elucidated. We present a typical case of such management via laparoscopic surgery, and include a surgical video. Case presentation: A woman in her 20s experienced fever and right lower quadrant pain and distension on postpartum day 2. Pelvic examination revealed a hump on the vaginal wall on the right side of the uterine cervix, and ultrasonography revealed a hematoma. Contrast-enhanced computed tomography revealed no active extravasation into the hematoma. Conservative antibiotic treatment was started; however, on postpartum day 6, her pain increased and her C-reactive protein concentration and white blood cell count were high. Magnetic resonance imaging revealed a paravaginal/upper vaginal wall hematoma (80 x 70 x 63 mm) located to the right of the uterus and bladder. Hence, laparoscopic drainage was performed on postpartum day 7. The retroperitoneal hematoma was incised and drained. The source of bleeding was the right vaginal vein, and bleeding was halted via electrocoagulation. The patient's symptoms improved immediately, and the postoperative course was uneventful. Clinical discussion: The laparoscopic approach enabled immediate hemostasis and identification of the source of bleeding. The drainage route was cleaner than would be possible via a vaginal approach, possibly preventing postoperative retrograde re-infection. Conclusion: Laparoscopic surgery for postpartum retroperitoneal hematoma with infection was useful for both drainage and hemostasis.

Preeclampsia, characterized by high blood pressure and proteinuria during pregnancy, causes serious complications in both the mother and the fetus. Although there have been several studies on the causes of preeclampsia, the detailed mechanism of this disease remains unclear. Moreover, a few reports have focused on the causes of preeclampsia in number of weeks at onset. The present study aimed to elucidate the differences between early‑ and late‑onset preeclampsia. This study enrolled patients with preeclampsia from January 2014 to December 2020. They were classified into early‑ (<34 weeks) and late‑onset (≥34 weeks) preeclampsia groups. The expression profiles of 770 immune‑related genes were studied in the placental tissue from five patients each in the early‑ and late‑onset groups. The expression of CD200 in the trophoblasts of the placenta of 26 and 27 patients in early‑ and late‑onset groups, respectively, was also analyzed using immunostaining. Analysis of extracted RNA indicated that CD200 was significantly upregulated in the early‑onset group compared with late‑onset group and normal control. Immunostaining for CD200 demonstrated a significantly increased expression in the early‑onset group compared with the late‑onset group. The present study demonstrated that upregulation of CD200, which belongs to the immunoglobulin superfamily and is recognized as a molecule that acts in immune tolerance via inhibition of classical macrophage activation, may be associated with early‑onset preeclampsia, although it remains unknown whether upregulation of CD200 expression is a cause or effect of the development of early‑onset preeclampsia. Early‑onset preeclampsia might have a different mechanism from that of late‑onset; thus, further studies are needed to clarify the mechanism of these conditions for adequate treatment.

Background: Ovarian carcinosarcoma (OCS) is a rare, highly aggressive, and treatment-resistant tumor. Some important advances in chemotherapy have been reported, including an anti-vascular endothelial growth factor antibody, bevacizumab (Bev)-containing regimen, and a poly-ADP ribose polymerase (PARP) inhibitor, olaparib. Olaparib is specifically a treatment option for OCSs with breast cancer gene (BRCA) mutations, and the clinical study on the combination of olaparib and Bev was reported for homologous recombination deficient epithelial ovarian cancer. However, there are no reports on treating advanced OCS with BRCA mutations by olaparib plus Bev effectively. In this study, to the best of our knowledge, we report the first case of successful management of multiple liver and para-aortic metastases of OCS with a BRCA mutation using olaparib plus Bev. Case: A 75-year-old woman presented to the hospital with complaints of abdominal distension. A staging laparotomy and histological analysis revealed a primary OCS. She received platinum doublet regimens as adjuvant chemotherapy. As myChoice (R) CDx test of the surgical specimen revealed a BRCA2 mutation, the combination regimen of olaparib (400 mg daily) plus Bev (15 mg/kg every three weeks) was chosen as the maintenance therapy. After four months of this chemotherapy, a computed tomography scan revealed significant shrinkage of both the liver metastases and para-aortic lymph nodes. Progression-free survival has been noted for over 14 months. Conclusions: The combination therapy of olaparib plus Bev could be a potential therapeutic option for advanced OCS.

BACKGROUND:The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone.OBJECTIVES:The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD.METHODS:This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD.RESULTS:Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively.CONCLUSIONS:Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.