Propensity of the tight mid-flexion and loose flexion gap despite the adjustment of extension and flexion gaps in Oxford unicompartmental knee arthroplasty: retrospective study.

PURPOSE: A well-balanced joint gap is necessary in Oxford unicompartmental knee arthroplasty (OUKA) to prevent mobile-bearing dislocation. While the gaps between 20° (extension) and 100° (flexion) are precisely adjusted using the incremental mill system, there has been insufficient evaluation of gaps in other angles. We hypothesized that the gap is not always the same in other angles. This retrospective study aimed to evaluate the gap in full-extension (0°), mid-flexion (60°) and deep flexion (130°) for comparison with those in extension and flexion gaps. METHODS: We evaluated 119 knees in 83 patients (51 females, 31 males, aged 71.9 years). The full-extension and mid-flexion gaps were compared with the extension gap, and the deep flexion gap was contrasted with the flexion gap. Each gap was classified into isometric, tight or loose, for evaluation of contributing factors. RESULTS: Although the full-extension gap tended to be isometric (45%), the mid-flexion tended to be tight (48%), whereas the deep-flexion was loose in most knees (84%) (P = 0.002). The tight mid-flexion and loose deep flexion gap pattern accounted for 44% of the total knees, especially so with smaller femoral components (P = 0.004). CONCLUSION: Our results highlight the propensity of tight mid-flexion and loose flexion gap despite the adjustment of extension and flexion gaps in OUKA. Although the effect of such a minor gap imbalance is still unknown, the pattern was more prevalent in patients with smaller-sized femoral components. Use of a larger femoral component may equalize the gap throughout the motion arc.

Half-value layer measurements using solid-state detectors and single-rotation technique with lead apertures in spiral computed tomography with and without a tin filter.

Solid-state detectors (SSDs) may be used along with a lead collimator for half-value layer (HVL) measurement using computed tomography (CT) with or without a tin filter. We aimed to compare HVL measurements obtained using three SSDs (AGMS-DM+ , X2 R/F sensor, and Black Piranha) with those obtained using the single-rotation technique with lead apertures (SRTLA). HVL measurements were performed using spiral CT at tube voltages of 70-140 kV without a tin filter and 100-140 kV (Sn 100-140 kV) with a tin filter in increments of 10 kV. For SRTLA, a 0.6-cc ionization chamber was suspended at the isocenter to measure the free-in-air kerma rate ( K ˙ air ) values. Five apertures were made on the gantry cover using lead sheets, and four aluminum plates were placed on these apertures. HVLs in SRTLA were obtained from K ˙ air decline curves. Subsequently, SSDs inserted into the lead collimator were placed on the gantry cover and used to measure HVLs. Maximum HVL differences of AGMS-DM+ , X2 R/F sensor, and Black Piranha with respect to SRTLA without/with a tin filter were - 0.09/0.6 (only two Sn 100-110 kV) mm, - 0.50/ - 0.6 mm, and - 0.17/(no data available) mm, respectively. These values were within the specification limit. SSDs inserted into the lead collimator could be used to measure HVL using spiral CT without a tin filter. HVLs could be measured with a tin filter using only the X2 R/F sensor, and further improvement of its calibration accuracy with respect to other SSDs is warranted.

Risk factors predicting pathological degradation after cervical excision in cervical intraepithelial neoplasia grade II P16-positive patients over 25 years old: a cross-sectional study.

Background: Cervical intraepithelial neoplasia (CIN) is a collective term for pre-cancerous lesions associated with cervical invasive carcinoma. Treatment options depend on the development and progression of the disease. Especially for patients with CINII grade who are aged 25 years and older and have fertility requirements, it is a clinical challenge to determine whether to proceed with conservative or excisional treatment. Excisional treatment increases the risk of overtreatment outcomes, such as cervical insufficiency, preterm labor, miscarriage, and premature rupture of membranes, in young women with childbearing potential. P16 immunohistochemical staining has greatly improved the consistency of CINII patient's diagnosis. The aim of this study was to analyze the risk factors predicting pathological degradation after cervical excision in cervical intraepithelial neoplasia grade II P16-positive patients over 25 years old, and to provide information to help optimize clinical treatments patients with CINII disease. Methods: Single-factor and logistic regression models were used to analyze the risk factors for pathological downgrading in the CINII/P16-positive (+) group. The predicted probability of pathological downgrading in the CINII/P16(+) group of patients was calculated according to the logistic regression model to generate a new variable multi-indicator association for receiver operating characteristic (ROC) curve plotting to determine the predictive ability. Results: A total of 248 women who met the inclusion and exclusion criteria were included. Statistical analysis showed that the CINII/P16(+) group had a higher pathological downgrading rate compared with the CINIII group after cold knife conization (CKC) (χ2=6.26, P=0.012). Univariate factors showed that the differences were statistically significant when comparing age, number of biopsy-involved quadrants, menopausal status, and involvement of glands, respectively (P<0.05). In contrast, the differences were not statistically significant when comparing cytological findings, type of transformation zone, high-risk human papilloma virus (HR-HPV) testing, abortion status, pregnancy frequency, time from diagnosis to CKC and Ki67 percentage between the two groups. Multifactorial logistic regression showed that the extent of biopsy CINII involvement [odds ratio (OR), 1.589], menopausal status (OR, 4.031), and glandular involvement (OR, 5.549) were all independent risk factors for pathological downgrading in the CINII/P16(+) patient group (P<0.05). The order of significance of the areas under the ROC curve (AUCs) was as follows: combined multiple indicators (AUC 0.716) > gland involvement (AUC 0.625) > biopsy CINII involvement extent (AUC 0.614) > menopausal status (AUC 0.565). Conclusions: A higher rate of pathological downgrading after CKC was found in CINII/P16-positive patients who were aged over 25 years. Overtreatment exists in patients with CINII/P16-positive diagnosis. Independent factors for pathological downgrading were identified by the factors including if the lesion involved the gland, the extent of CINII involvement on biopsy, and menopausal status.

Restricted Kinematically Aligned Total Knee Arthroplasty Following Failed Oxford Unicompartmental Knee Arthroplasty.

In this report, we describe how to revise a failed Oxford unicompartmental knee arthroplasty to kinematically aligned total knee arthroplasty (TKA). Its benefits are the maintenance of the native joint line along with the avoidance of supplemental parts, such as metal augments and stems. This can be applied to patients whose medial tibial cortex is well preserved. The distal cutting plane and rotation alignment are decided before the removal of the femoral component. The tibial cutting plane is up to 12 mm below the lateral joint surface and the varus is up to 5° below the extramedullary rod. Eventually, the native joint line and alignment along with the soft tissue envelope can be well maintained, similar to the restricted kinematically aligned TKA.

Characteristic of Endometrial Stromal Sarcoma by Algorithm of Potential Biomarkers for Uterine Mesenchymal Tumor.

The benign tumor uterine leiomyoma (UL) develops from the smooth muscle tissue that constitutes the uterus, whereas malignant tumor uterine sarcoma develops from either the smooth muscle tissue or stroma and is different from UL and endometrial cancer. Uterine sarcoma is broadly classified into three types: uterine leiomyosarcoma, endometrial stromal sarcoma (ESS), and carcinosarcoma. Although uterine leiomyosarcoma and ESS are both classified as uterine sarcoma, they significantly differ in terms of their sites of occurrence, symptoms, and treatment methods. Uterine leiomyosarcoma develops from the muscle tissue constituting the wall of the uterus and accounts for approximately 70% of all uterine sarcoma cases. In contrast, ESS develops from the stromal tissue beneath the endometrium and accounts for approximately 25% of all uterine sarcoma cases. ESS is classified as either low grade (LG) or high grade (HG). This case report aimed to highlight the importance of histopathologic examinations based on surgical specimens. Herein, we reported the case of a 45-year-old woman suspected of having submucosal leiomyoma of the uterus based on imaging results. Transvaginal ultrasonography and endometrial biopsy or partial dilation and curettage were performed. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 32-mm mass projecting from the posterior wall of the uterus into the uterine cavity. T2-weighted imaging revealed a low signal within the mass; thus, submucosal UL was suspected. Histopathologic examination of surgical specimens obtained from a patient suspected of having submucosal UL after contrast-enhanced MRI indicated that the patient had ESS. Despite the remarkable advancements in medical imaging technology, the accuracy of contrast-enhanced MRI for detecting uterine mesenchymal tumors is limited. Therefore, histopathologic diagnosis based on surgical specimens should be performed when medical grounds for diagnosing a benign tumor on contrast-enhanced MRI are lacking.

Histopathological Findings of Ectopic Pregnancy in Contraceptive-Wearing Woman.

In normal pregnancy, the egg is fertilized in the fallopian tube. It later moves into the uterus, where it implants into the uterine endometrium. Therefore, implantation of the fertilized egg into the endometrium is not observed in many women using contraceptives. However, if the fallopian tubes are diseased or abnormal, the fertilized egg cannot travel to the endometrium. Thus, the fertilized egg is implanted in tissues other than the uterus, resulting in an ectopic pregnancy. In most cases of ectopic pregnancy, the fertilized egg is implanted into the left or right fallopian tube or in tissues other than the fallopian tubes such as the ovary. With laparoscopic surgery, the scars are small, and the pain and physical burden are also much lesser than those with open surgery; thus, the patient can be rehabilitated immediately. Laparoscopic surgery is preferred for the termination of ectopic pregnancies because the patients recovered quickly physically after surgery and can be discharged in a short period. This paper presents our experience in treating a 37-year-old woman who had a tubal pregnancy despite using a contraceptive. Contrast-enhanced magnetic resonance imaging showed a gestational sac within the right fallopian tube. Laparoscopic surgery was performed to resect the right fallopian tube. Pathological examination suggested that the ectopic pregnancy occurred at the organogenesis stage 9 weeks after fertilization. The pathological findings revealed subpopulations of cells from the ectoderm that were separated from other cells and more specifically formed spinal and ovarian structures. The implantation of the fertilized egg into the endometrium is not observed in many women using contraceptives. However, in rare cases, ectopic pregnancy occurs in women using contraceptives; thus, caution is necessary in diagnosis and treatment. This report presents valuable surgical pathological findings from such a rare case of ectopic pregnancy to understand the differentiation into each tissue during organogenesis.

Familial Gastrointestinal Stromal Tumor Associated with Zebra-like Pigmentation.

Purpose: According to clinical studies, gastrointestinal stromal tumors (GISTs) are predominantly sporadic. GISTs associated with familial syndromes are very rare, and most patients exhibit wild-type KIT and platelet-derived growth factor alpha (PDGFRA). To date, GISTs associated with germline KIT pathogenic variants have been observed in only 30 kindreds worldwide. The efficacy of imatinib, a multityrosine kinase inhibitor, in patients with GIST presenting germline KIT variants has been poorly reported, and the efficacy in clinical trials of treatments with tyrosine kinase inhibitors remains unclear. Therefore, imatinib is not yet recommended for treating GIST patients with germline KIT variants. Experimental Design: We performed cancer genomic testing on samples from a 32-year-old male patient with advanced GISTs throughout the upper stomach and cutaneous hyperpigmentation to determine diagnosis and treatment strategies. Results: We detected a germline W557R pathogenic variant of KIT. The patient was diagnosed with familial multinodular GIST based on the clinical findings and familial history of malignant tumors. Treatment with imatinib resulted in long-term regression of GISTs. Conclusions: Pathogenic variants detected by cancer genome testing can be used to diagnose malignant tumors and select new therapeutic agents for patients with advanced malignancies.

Energy-based Hp(3) measurement using solid-state detector.

This study aimed to develop an energy-based Hp(3) measurement method using a solid-state detector (SSD). Incident and entrance surface air kerma were measured using an ionization chamber placed free-in-air and in front of an anthropomorphic or slab phantom. Subsequently, three SSDs were placed free-in-air, and half-value layer and readings were obtained. After measurements, an X-ray beam quality correction factor $\left ({{k}}_{{Q},{{Q}}_{\mathbf{0}}}^{{SSD}}\right)$, backscatter factor (BSF) and conversion factor from incident air kerma to Hp(3) (C3) were determined. Then, the incident air kerma by SSD $\left ({{K}}_{{a},{i}}^{{SSD}}\right )$, Hp(3) and Hp(3)/${{K}}_{{a},{i}}^{{SSD}}$ were calculated. The ${{k}}_{{Q},{{Q}}_{\mathbf{0}}}^{{SSD}}$ was almost consistent for all SSDs. The C3 and BSF were found to increase as tube potential increased. The Hp(3)/${{K}}_{{a},{i}}^{{SSD}}$ calculated with the anthropomorphic and slab phantoms were consistent within 2.1% and 2.6% for all SSDs, respectively. This method improves the energy dependence of Hp(3) measurement and can estimate the Hp(3) measurement error for dedicated Hp(3) dosemeters.

Molecular Histopathology for Establishing Diagnostic Method and Clinical Therapy for Ovarian Carcinoma.

Ovarian carcinoma (OC) is considered the deadliest gynecological malignancy. It is typically diagnosed in the advanced stages of the disease, with metastatic sites widely disseminated within the abdominal cavity. OC treatment is challenging due to the high rate of disease recurrence, which is further complicated by acquired chemoresistance caused by the reversion of the pathological variant. Therefore, more effective treatments are still being sought. Histologically, OC is classified into serous, mucinous, endometrioid, clear cell, and transitional cell carcinomas and malignant Brenner tumor. Recent clinicopathological and molecular biological studies demonstrated that these subtypes differ in histogenesis and anti-tumor agent sensitivity. In Japan, the incidence rates of the histological types of OC, namely, serous carcinoma, mucinous carcinoma, endometrioid carcinoma, and clear cell adenocarcinoma, are 39%, 12%, 16%, and 23%, respectively. Serous carcinoma is classified as high or low grade, with the former accounting for the overwhelming majority. In this study, the molecular pathological classification of OC has been described based on the characteristics of the two types of OC, types 1 and 2. Compared with Europe and the United States, Japan has a higher prevalence of type 1 OC and a lower prevalence of type 2 OC. The prevalence of each type of OC varies by race. It has been elucidated that the prevalence rate of each type of ovarian cancer in Asian countries is similar to that in Japan. Thus, OC is a heterogeneous disease. Furthermore, OC has been attributed to molecular biological mechanisms that vary among tissue subtypes. Therefore, it is necessary to conduct treatment based on accurate diagnoses of each tissue type and establish an optimal treatment strategy, and now is the transition period.

Treatment With Antitumor Agents Recommended by Cancer Genome Panel for Uterine Leiomyosarcoma.

To date, cancer genomic medicine, using cancer gene panel covered by health insurance from June 2019, has been performed for advanced malignant tumors under public medical insurance. In gynecology, the first-line treatment for uterine leiomyosarcomas, which is a mesenchymal uterine tumor, is surgery. In uterine leiomyosarcoma cases, recurrence is observed within 2 years postoperatively; however, to date, clinical trials have not shown efficacy with existing antitumor agents. We noted efficacy in two cases with advanced/recurrent uterine leiomyosarcoma using an antitumor agent selected on the basis of cancer gene panel testing results. Following uterine leiomyosarcoma diagnosis, they underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy as standard surgical treatment. After the surgical treatment, the imaging test revealed recurrent tumors; subsequently, they were treated with doxorubicin alone or doxorubicin combined with Gemzar. However, cancer genome gene panel test was performed because the malignant tumor worsened. Based on the cancer genome gene panel test results, the two cases with advanced uterine leiomyosarcoma were associated with increased tumor mutational burden (TMB) or pathogenic variants (PVs) of AKT serine/threonine kinase 1 (AKT1). Therefore, treatment with pembrolizumab, which is a drug covered by insurance for patients with TMB-high, or treatment with kinase inhibitors for patients with PVs in AKT, was considered. Cancer genomic medicine using cancer gene panel provides a new treatment strategy for intractable malignant tumors. This study aimed to discuss the usefulness of cancer genomic medicine by cancer gene panel testing using the cases of advanced and recurrence uterine leiomyosarcoma and the latest findings.

A Novel High-Throughput Screening Method for a Human Multicentric Osteosarcoma-Specific Antibody and Biomarker Using a Phage Display-Derived Monoclonal Antibody.

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen-antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody-drug conjugate targeting of these specific proteins may be promising for clinical applications.

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer.

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.

Appropriate Amounts and Activity of the Wilms' Tumor Suppressor Gene, wt1, Are Required for Normal Pronephros Development of Xenopus Embryos.

The Wilms' tumor suppressor gene, wt1, encodes a zinc finger-containing transcription factor that binds to a GC-rich motif and regulates the transcription of target genes. wt1 was first identified as a tumor suppressor gene in Wilms' tumor, a pediatric kidney tumor, and has been implicated in normal kidney development. The WT1 protein has transcriptional activation and repression domains and acts as a transcriptional activator or repressor, depending on the target gene and context. In Xenopus, an ortholog of wt1 has been isolated and shown to be expressed in the developing embryonic pronephros. To investigate the role of wt1 in pronephros development in Xenopus embryos, we mutated wt1 by CRISPR/Cas9 and found that the expression of pronephros marker genes was reduced. In reporter assays in which known WT1 binding sequences were placed upstream of the luciferase gene, WT1 activated transcription of the luciferase gene. The injection of wild-type or artificially altered transcriptional activity of wt1 mRNA disrupted the expression of pronephros marker genes in the embryos. These results suggest that the appropriate amounts and activity of WT1 protein are required for normal pronephros development in Xenopus embryos.

Characteristic of Concurrent Uterine Lipoleiomyoma and Hemangioma by Algorithm of Candidate Biomarkers for Uterine Mesenchymal Tumor.

(1) Background/Aim: In clinical practice, uterine lipoleiomyomas are variants of uterine leiomyomas that are often found incidentally and do not require surgical treatment unless the patient is symptomatic. Therefore, these should be clinically differentiated from lesions that need surgical treatment. Conversely, hemangiomas, or blood vessel benign tumors, rarely develop in the uterus; however, many clinical complications such as abdominal pain and excessive vaginal bleeding result from a uterine hemangioma. Hemangiomas can occur at any age and primarily affect pregnant women. (2) Materials and Methods: The oncological properties of uterine lipoleiomyoma and hemangioma in adults were investigated using molecular pathological examination on tissue excised from patients with a uterine tumor. (3) Results: Through molecular pathological studies, which included potential biomarkers for uterine mesenchymal tumors, a differential diagnosis was established for a case of mesenchymal tumor. Herein, we report a 54-year-old non-pregnant woman who presented with vaginal bleeding and underwent hysterectomy after detection of a 140 × 100 mm intramural mass diagnosed as a concurrent uterine hemangioma and lipoleiomyoma after molecular histopathologic examinations. (4) Conclusion: As far as we know, our case is the first patient of concurrent uterine hemangioma and lipoleiomyoma. Hence, the possibility of several types of mesenchymal tumors must be considered in the differential diagnosis of patients with abnormal vaginal bleeding. As such, molecular pathological examination and close monitoring of the MRI results should be conducted by medical staff while considering the patient's desire for pregnancy, including surgical treatment options for uterine hemangioma.

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics.

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Reducing stray radiation with a novel detachable lead arm support in percutaneous coronary intervention.

BACKGROUND: Placing radioprotective devices near patients reduces stray radiation during percutaneous coronary intervention (PCI), a promising technique for treating coronary artery disease. Therefore, lead arm support may effectively reduce occupational radiation dose to cardiologists. PURPOSE: We aimed to estimate the reduction of stray radiation using a novel detachable lead arm support (DLAS) in PCI. MATERIALS AND METHODS: A dedicated cardiovascular angiography system was equipped with the conventional 0.5-mm lead curtain suspended from the table side rail. The DLAS was developed using an L-shaped acrylic board and detachable water-resistant covers encasing the 0.5-, 0.75-, or 1.0-mm lead. The DLAS was placed adjacent to a female anthropomorphic phantom lying on the examination tabletop at the patient entrance reference point. An ionization chamber survey meter was placed 100 cm away from the isocenter to emulate the cardiologist's position. Dose reduction using the L-shaped acrylic board, DLAS, lead curtain, and their combination each was measured at five heights (80-160 cm in 20-cm increments) when acquiring cardiac images of the patient phantom with 10 gantry angulations, typical for PCI. RESULTS: Median dose reductions of stray radiation using the L-shaped acrylic board were 9.0%, 8.8%, 12.4%, 12.3%, and 6.4% at 80-, 100-, 120-, 140-, and 160-cm heights, respectively. Dose reduction using DLAS with a 0.5-mm lead was almost identical to that using DLAS with 0.75- and 1.0-mm leads; mean dose reductions using these three DLASs increased to 16.2%, 45.1%, 66.0%, 64.2%, and 43.0%, respectively. Similarly, dose reductions using the conventional lead curtain were 95.9%, 95.5%, 83.7%, 26.0%, and 19.6%, respectively. The combination of DLAS with 0.5-mm lead and lead curtain could increase dose reductions to 96.0%, 95.8%, 93.8%, 71.1%, and 47.1%, respectively. CONCLUSIONS: DLAS reduces stray radiation at 120-, 140-, and 160-cm heights, where the conventional lead curtain provides insufficient protection.