Successful surgical treatment of postmyomectomy uterine diverticulum: a case report.

BACKGROUND: Uterine diverticulum is classified into congenital and acquired types. The acquired type is caused by caesarean scar syndrome, which occurs after caesarean section. There are no detailed reports on diverticulum after enucleation of uterine fibroids. Most cases are treated with hysteroscopy or laparoscopy, but a management consensus is lacking. We treated a patient with a uterine diverticulum that had formed after uterine fibroid enucleation by combining hysteroscopic and laparoscopic treatments. CASE PRESENTATION: The patient was a 37-year-old Japanese woman, G1P0. A previous doctor had performed abdominal uterine myomectomy for a pedunculated subserosal uterine fibroid on the right side of the posterior wall of the uterus near the internal cervical os. Menstruation resumed postoperatively, but a small amount of dark-red bleeding persisted. MRI two months after the myomectomy revealed a diverticulum-like structure 3 cm in diameter, communicating with the uterine lumen, on the right side of the posterior wall of the uterus. Under suspicion of uterine diverticulum after uterine fibroid enucleation, the patient sought treatment at our hospital approximately four months after the myomectomy. Through a flexible hysteroscope, a 5-mm-diameter fistula was observed in the posterior wall of the uterus, and a contrast-enhanced pocket, measuring approximately 3 cm, was located behind it. Uterine diverticulum following enucleation of a uterine fibroid was diagnosed, and surgery was thus deemed necessary. The portion entering the fistula on the internal cervical os side was resected employing a hysteroscope. Intra-abdominal findings included a 4-cm mass lesion on the posterior wall on the right side of the uterus. The mass was opened, and the cyst capsule was removed. A 5-mm fistula was detected and closed with sutures. Resuturing was not performed after dissection of the right round ligament due to tension. The postoperative course has been good to date, with no recurrence. CONCLUSION: Uterine diverticula after myomectomy may be treated with a combined laparoscopic and hysteroscopic approach, similar to caesarean scar syndrome.

Multiple Immunofluorescence Imaging Analysis Reveals Differential Expression of Disialogangliosides GD3 and GD2 in Neuroblastomas.

BACKGROUND: Peripheral neuroblastic tumors (pNTs) are the most common childhood extracranial solid tumors. There are several therapeutic strategies targeting disialoganglioside GD2. Disialoganglioside GD3 has become a potential target. However, the mechanism by which pNTs express GD3 and GD2 remains unclear. We investigated the combined expression status of GD3 and GD2 in pNTs and delineated their clinicopathological values. METHODS: GD3 and GD2 expression was examined in pNT tissue samples (n = 35) using immunohistochemistry and multiple immunofluorescence imaging. RESULTS: GD3 and GD2 expression was positive in 32/35 and 25/35 samples, respectively. Combinatorial analysis of GD3 and GD2 expression in neuroblastoma showed that both were heterogeneously expressed from cell to cell. There were higher numbers of GD3-positive and GD2-negative cells in the low-risk group than in the intermediate-risk (P = 0.014) and high-risk (P = 0.009) groups. Cases with high proportions of GD3-positive and GD2-negative cells were associated with the International Neuroblastoma Staging System stage (P = 0.004), Children's Oncology Group risk group (P = 0.001), and outcome (P = 0.019) and tended to have a higher overall survival rate. CONCLUSION: We demonstrated that neuroblastomas from low-risk patients included more GD3-positive and GD2-negative cells than those from high-risk patients. Clarifying the heterogeneity of neuroblastoma aids in better understanding the biological characteristics and clinical behavior.

Adrenal cytomegaly with elevated serum androgen levels in a patient with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is infrequently associated with adrenocortical carcinoma (ACC) or non-hormone-producing adrenal cytomegaly, but we recently, encountered a single case of adrenal cytomegaly in a patient with BWS, which was difficult to distinguish from androgen-producing adrenocortical carcinoma (ACC). Here, we describe the case of a 4-month-old female who presented with clitoromegaly, hemihypertrophy, and an adrenal mass identified during the prenatal period. The mass was located in detected at the left suprarenal region and detected at 20 weeks of gestational age. At birth, she also presented with clitoromegaly and elevated serum levels of 17α-hydroxyprogesterone, dehydroepiandrosterone, and testosterone at birth and experienced hyper-insulinemic hypoglycemia, which improved following diazoxide therapy. We initially suspected androgen-producing ACC with metastasis and the left adrenal mass was resected accordingly when the patient reached 4 months of age. However, histological examination revealed adrenal cytomegaly. Genetic analysis revealed paternal uniparental disomy, and the patient was finally diagnosed as having BWS. Resection of the left adrenal gland restored the serum androgen levels to normal physiological levels without any recurrence. While it is reasonably well known that BWS is sometimes accompanied by virilization due to androgen-producing ACC, our findings are among the first to suggest that adrenal cytomegaly can also increase androgen hormone production. Thus, we propose that adrenal cytomegaly should be considered one of the differential diagnoses when accompanied with hyperandrogenism in BWS patients.

Fatal Embolic ST-Elevation Myocardial Infarction Secondary to Healed-Phase Mitral Valve Infective Endocarditis.

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.

[A Case of Advanced Gastric Cancer with Bone Marrow Metastasis Treated with Low-Dose Combination Chemotherapy Containing S-1 and Docetaxel].

A 77-year-old woman was admitted to our hospital with complaints of lumbago. Based on MRI, bone marrow biopsy, and upper endoscopy, she was diagnosed as having advanced gastric cancer accompanied by bone marrow metastasis and multiple bone metastases. She underwent combination chemotherapycontaining S-1 and docetaxel(TXT). However, during the first course of chemotherapy, she developed Grade 4 neutropenia and sepsis, and her ADL worsened. The anticancer agent doses were reduced drasticallyto 40% of the initial dose from the next course of chemotherapy. She was able to continue treatment without developing severe adverse events, and the disease did not progress for 11 months. However, during the 6 course of chemotherapy, she developed Grade 4 neutropenia and sepsis again, and it became difficult to continue treatment. Subsequent S-1 monotherapywas not efficacious, and she died 17 months after diagnosis. From the view of persistence and efficacy, we believe that low-dose combination chemotherapycontaining S-1 and TXT maybe a suitable regimen for advanced gastric cancer with bone marrow metastasis.

Overexpression of PGC1α and accumulation of p62 in apocrine carcinoma of the breast.

Apocrine carcinoma is categorized as a special type of breast carcinoma because of its specific morphological features. To clarify the characteristics of apocrine carcinoma from the point of view of the mitochondrial profile, we conducted a comparative study between apocrine and non-apocrine carcinomas. The expressions of mitochondrial related factors (PGC1α, Nrf1, Nrf2, mtTFA and COX4) were examined in a testing set of breast cancer tissue. Apocrine carcinomas showed a clear tendency towards higher mRNA expression levels of PGC1α than non-apocrine carcinomas. The expression of the selected factor, PGC1α, as well as that of p62 was further examined. The results revealed that apocrine carcinomas showed a higher immunohistochemical positivity rate for PGC1α (21.3% vs. 3.2%; P = 0.008), and that the mRNA expression level of PGC1α was significantly higher in apocrine carcinoma than in non-apocrine carcinoma (P = 0.007). The immunohistochemical positivity rate for p62 protein was also higher in apocrine carcinomas (44.7% vs. 21.0%; P = 0.015), although no significant difference in the p62 mRNA expression level was detected between the two types of carcinoma (P = 0.633). In conclusion, this study revealed that apocrine carcinoma overexpressed PGC1α contributing to mitochondrial biogenesis, and also p62 protein accumulation.

Case report: Anti-N-methyl-D-aspartate receptor antibody-associated autoimmunity triggered by primary central nervous system B-cell lymphoma.

Background: We herein detail our experience with a unique patient with a primary central nervous system (PCNS) B-cell lymphoma concomitant with anti-N-methyl-d-aspartate receptor (NMDAR) antibodies that satisfied the criteria of "probable anti-NMDAR encephalitis (ProNMDARE)" based on the Graus criteria 2016. Case presentation: A 73-year-old Japanese woman presented with acute pyrexia, agitation, and disturbance of consciousness. She gradually developed a reduction in speech frequency and truncal dystonia causing abnormal posture. Brain magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the bilateral frontal lobes, and her cerebrospinal fluid revealed mild pleocytosis. She was diagnosed with acute encephalitis and treated with acyclovir and intravenous dexamethasone; however, no improvement was observed. She was transferred to our hospital 6 weeks after the onset of her symptoms, and anti-NMDAR antibodies were identified in her cerebrospinal fluid through indirect immunolabeling with rat brain frozen sections and cell-based assays with NR1/NR2 transfected HEK cells. Follow-up MRI showed enlargement of the lesions in the right frontal lobe with gadolinium enhancement, suggesting a brain tumor. Stereotactic surgery was implemented, with subsequent pathological examination revealing that the tumor was consistent with diffuse large B-cell lymphoma (DLBCL) without evidence of systemic satellite lesions. Stereotactic irradiative therapies were then added to her treatment regimen, which partly improved her neurological symptoms with only mild cognitive dysfunction still remaining. A decrease in anti-NMDAR antibody titer was also confirmed after immunotherapy and tumor removal. Conclusions: We herein report our experience with a novel case of PCNS-DLBCL masquerading as anti-NMDAR encephalitis that satisfied the diagnostic criteria of "proNMDARE." Treatment, including tumor removal, ameliorated disease severity and antibody titers of the patient. Our findings suggest that anti-NMDAR antibody-associated autoimmunity can be triggered by PCNS B-cell tumors, although primary brain tumors need to be excluded before establishing a diagnosis of autoimmune encephalitis.

Clinical impact of central nervous system-directed therapies on intravascular large B-cell lymphoma: A single institution's experience.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS-directed therapy or standard therapy alone. CNS-directed therapy was associated with a significantly better 2-year CNS-free survival (100% vs. 63%, p = 0.0191), despite no significant effects on progression-free or overall survival. Further studies should assess CNS-focused treatment in patients with IVLBCL with or without primary CNS involvement.

Tissue Thickness Interferes With the Estimation of the Immunohistochemical Intensity: Introduction of a Control System for Managing Tissue Thickness.

CONTEXT AND OBJECTIVE: The conversion of immunohistochemical (IHC) results from 3-dimensional tissue to a 2-dimensional visual image without considering tissue thickness poses a considerable risk of misleading IHC intensities. The present study aimed to clarify whether tissue thickness interferes with the estimation of IHC staining intensity and to introduce a control system to manage it. DESIGN: We prepared cell lines that are used as controls for human epidermal growth factor receptor 2 (HER2) IHC (MDA-MB-231, MDA-MB-175VII, MDA-MV-453, and SK-BR-3), a polyclonal antibody for HER2, an interferometry to measure the tissue thickness of formalin-fixed paraffin-embedded sections, a microscope with a Halogen or an LED light source, a complementary metal-oxide semiconductor camera in which the output signal can be corrected to γ=1, and a program to estimate color elements (hue, saturation, and luminance). It was examined whether tissue thickness interferes with the experimental scoring systems and practical classification of the routine HER2 scoring system. RESULTS: A noncellular control was shown to be better than a cellular control for managing tissue thickness. The IHC intensity for HER2 was correlated with tissue thickness (R2=0.8094), even under the less-standardized condition, but this correlation was better under the improved standardized condition using corrected γ=1 (R2=0.9282). Discrepancies in practical HER2 scores were increased in sections with thicknesses <2 and >5 µm. A control system to manage tissue thickness was introduced. CONCLUSIONS: Tissue thickness interferes with the estimation of the IHC intensity of HER2 in both experimental and practical scoring systems. A control system for managing tissue thickness is essential to increase the benefits of IHC as a standardized assay for clinical applications.

Mixed ductal-lobular carcinoma: an analysis of CDH1 DNA copy number variation and mutation.

BACKGROUND: Mixed ductal-lobular carcinoma (MDL) of the breast is poorly understood. Dysfunction of E-cadherin, a cell adhesion protein encoded by the CDH1 gene located on 16q22.1, causes loss of cell adhesion and cellular polarity in lobular carcinoma (LC). This study focuses the aberrations of CDH1 in LC, ductal carcinoma (DC), and MDL to investigate the pathogenesis of MDL. METHODS: The CDH1 DNA value (ratio of CDH1 copy number to the reference gene, RNase P) was calculated by digital polymerase chain reaction analysis of a total of 113 breast carcinoma cases (51 LCs, 54 DCs, and 8 MDLs). CDH1 gene mutation assay was performed for 20/51 LCs, 8/54 DCs, and 8 MDLs cases. RESULTS: The CDH1 DNA values were lower in LCs (average: 0.664) than in DCs (average: 1.296) (p < 0.000). In MDL, The CDH1 DNA values were significantly lower in LC areas (average: 0.58), compared to that of DC areas (average: 1.08) (p = 0.004), and there is no significant difference between the intermingled areas (average: 1.05) and DC areas (p = 0.775). Moreover, CDH1 mutations occurred more frequently in MDLs than in pure LCs and DCs. In one MDL case, the identical CDH1 mutation was found in LC and DC areas. CONCLUSION: Our study presented that MDL had more frequent CDH1 mutations. There were two possible processes for cancer cells in LC areas: one process was via DC areas with a common ancestor, and another was an independent process from DC areas.

Bladder mucosa-associated lymphoid tissue lymphoma progressed from chronic cystitis along with a comparative genetic analysis during long-term follow-up: a case report.

The pathogenesis of bladder marginal zone/mucosa-associated lymphoid tissue (MALT) lymphoma, which is the most common type of primary bladder lymphoma, has not been clarified. There are no reports that described histological and molecular time course of MALT lymphoma occurring in the bladder and the importance of the score on the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale during and after radiation therapy (RT). We present a case of MALT lymphoma with long-term comparative genetic analysis. A 77-year-old Japanese woman with hematuria and severe perineal pain was found to have a tumor-like lesion in the bladder trigone. She was diagnosed with cystitis based on the results of pathological examination and immunostaining after transurethral resection of the lesion. The second transurethral resection procedure was performed approximately 4 years after the first procedure because of recurrence of the hematuria and enlargement of a lesion in the left bladder wall. Postoperative pathologic examination confirmed a diagnosis of MALT lymphoma. Genetic analysis of immunoglobulin heavy chain (IGH) gene rearrangements showed more clonal progression from the first biopsy to the second. The patient then underwent RT, during which her perineal pain was exacerbated by radiation cystitis but finally decreased to a level less severe than that before treatment. The PUF patient symptom scale was useful to monitor her pain throughout the clinical course. No recurrence was detected more than 2 years after completion of RT.

Altered Immunohistochemical Expression Patterns of HLA Class I during the Clinical Course of Cervical Intraepithelial Neoplasia.

It is unclear how immunohistochemical expression patterns of HLA class I in the pre-malignant phase of cervical intraepithelial neoplasia (CIN) alter during the clinical follow-up period. The present study aimed to demonstrate the correlation between the immunohistochemical expression pattern of HLA class I and the CIN grade through repeated examinations during the clinical course. Expression patterns of HLA class I, p16INK4a, and PD-L1 were immunohistochemically examined using formalin-fixed paraffin-embedded (FFPE) sections of biopsy or conization samples that were obtained from 20 patients diagnosed with CIN. The mRNA expression levels of HLA class I were analyzed by real-time reverse transcription polymerase chain reaction using FFPE sections of 14 patients, who were examined metachronously during the follow-up period. HLA class I expression was limited to the lower part of the epithelial thickness (M1 pattern) in more than half of CIN1 cases, and was present throughout the epithelial thickness (M2 pattern) in one fourth of CIN1 and CIN2 cases approximately. Heterogeneous expression (H pattern) was detected in half of CIN2 and CIN3 cases and in the all of squamous cell carcinoma cases. Metachronous examinations revealed that these immunohistochemical patterns altered more frequently than the CIN grade. The rate of change of HLA class I mRNA expression level was higher in cases with a progressed immunohistochemical pattern compared to those with regressed immunohistochemical pattern. In conclusion, the immunohistochemical pattern of HLA class I expression is associated with the CIN grade, and it is alterable during the clinical course, especially in CIN2.

Magnetic resonance elastography-based prediction of hepatocellular carcinoma recurrence after curative resection.

BACKGROUND: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma. METHODS: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed. RESULTS: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001). CONCLUSION: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma.

Computed Tomography of Lymph Node Metastasis Before and After Radiation Therapy: Correlations With Residual Tumour.

BACKGROUND: Computed tomography (CT) performed after radiation therapy (RT) is used to detect residual lymph node (LN) metastasis. Here, we investigated which LN parameters on pre- and post-RT CT images correlated with residual tumour in patients with head and neck cancer. PATIENTS AND METHODS: We enrolled 23 patients who received RT. A total of 50 LNs were evaluated. Correlations between quantitative and qualitative findings and residual tumours were evaluated. RESULTS: The median patient age was 61 years. Thirty-one LNs were histologically confirmed to contain residual tumour. LNs with residual tumour had significantly longer short and long axes on post-RT CT images. A new finding of obscured margins after RT were significantly associated with the presence of residual tumour by univariate and multivariate analyses. CONCLUSION: Comparison of qualitative, LN parameters on pre- and post-RT CT images may improve the detection of residual tumour in patients with suspected residual or recurrent LN metastasis.

Partial chest wall radiation therapy for positive or close surgical margins after modified radical mastectomy for breast cancer without lymph node metastasis.

AIM: Whole-breast radiation therapy after breast-conserving surgery can control local recurrence with a long-term survival rate equivalent to that of radical mastectomy for patients with early breast cancer. However, the significance of radiation therapy for patients with positive/close margins after mastectomy remains controversial. Following radical mastectomy, no residual breast parenchyma remains, and thus radiation therapy of the entire chest wall may represent overtreatment in the patients, especially those without lymph node metastasis (N0). We therefore implemented partial chest wall radiation therapy for patients with N0 breast cancer and positive and/or close margins after mastectomy. METHODS: A total of 22 patients with N0 status but positive/close margins underwent partial chest wall radiation therapy to irradiate the predetermined clinical target volume, which had margins of at least 2 cm medial, lateral, superior, and inferior to the primary tumor bed. With reference to chest wall thickness, 4-10-MV photons or 5-8-MeV electrons with/without a bolus were delivered. The total dose was 50-66 Gy. We compared the results with those from 18 nonradiation therapy patients using Pearson's χ2 test. RESULTS: All patients in the partial chest wall radiation therapy group achieved good local control despite having a significantly higher proportion of positive margins (77.3%) compared with the nonradiation therapy group (27.8%) (P = 0.002). Both groups showed 100% recurrence- and disease-free survival. CONCLUSION: Partial chest wall radiation therapy may offer recurrence- and disease-free survival without local recurrence in N0 mastectomy patients with positive/close surgical margins.

Conjunctival lymphomas in Japanese monozygotic twins: A case report.

An individual with a twin who has developed leukemia or non-Hodgkin lymphoma (NHL) has an increased risk of developing the same disease, particularly with monozygotic twins. The few reported pairs of twins who developed NHL had similar primary sites and pathological subtypes. Here, we present the first reported cases of primary conjunctival NHL in both female monozygotic twins. Twin 1 was diagnosed with an extranodal marginal zone lymphoma (EMZL; Ann Arbor stage IE) in the right conjunctiva at 25 years old and a subsequent tumor in the left conjunctiva at 39 years, and was also histopathologically diagnosed as EMZL. No infiltration of other organs was detected and both lesions were surgically excised. At the age of 40 years, Twin 2 was diagnosed with an EMZL (Ann Arbor stage IE) in the right conjunctiva without infiltration of other organs and was treated with external beam radiation therapy rather than surgery. Complete remission was achieved in both twins; neither developed conjunctival recurrences. This study highlights the importance of examining the other, apparently healthy twin when one twin develops conjunctival lymphoma.

Changes in the Ki-67 labeling index between primary breast cancer and metachronous metastatic axillary lymph node: A retrospective observational study.

BACKGROUND: The Ki-67 labeling index (LI) is a well-known prognostic factor for primary breast cancer, but its clinical significance for metachronous axillary lymph node (ALN) recurrence has not been well documented. METHODS: Ki-67 expression in primary tumors (PTs) and ALN metastases (ALNMs) was evaluated in 21 patients and quantified to investigate the relationship between Ki-67 LIs in PTs and metachronous ALNMs. RESULTS: The median Ki-67 LIs in the PTs and ALNMs were 25.2% (range: 2.3-80.2%) and 70% (range: 10.4-97.4%), respectively. A majority of patients had higher Ki-67 LIs in ALNMs than in PTs (76.2%, 16/21). Disease-specific survival was significantly better in patients with a lower-than-median ALNM Ki-67 LI (P = 0.019, log-rank test). Receiver operating characteristic curves showed a PT Ki-67 LI of 62.8% as the optimal cutoff value and an ALNM Ki-67 LI of 65.1%. Accordingly, we divided the patients into four groups: PT Ki-67 LI lower than 62.8%/ALNM Ki-67 LI lower than 65.1%, PT Ki-67 LI lower/ALNM Ki-67 LI higher, PT Ki-67 LI higher/ALNM Ki-67 LI higher, and PT Ki-67 LI higher/ALNM Ki-67 LI lower. Disease-specific survival was significantly better in patients with Ki-67 LI lower/ALNM Ki-67 LI lower than in the other groups. CONCLUSION: This is the first study to show that the Ki-67 LI in metachronous ALNM is a prognostic factor for patients with metachronous ALN recurrence of breast cancer.