Early treatment with Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes) ameliorates post-partum hemorrhage with coagulopathy caused by amniotic fluid embolism in rabbits.

BACKGROUND: Amniotic fluid embolism is an unpredictable and sometimes lethal complication of childbirth. Fibrinogen γ-chain peptide-coated, ADP-encapsulated Liposomes (H12-(ADP)-liposomes), which were developed as a platelet substitute, may be useful to control postpartum hemorrhage with consumptive coagulopathy. OBJECTIVE: This study aimed to establish a hemodynamically stable amniotic fluid embolism animal model and evaluate the efficacy of H12-ADP-liposome infusion in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism-involved coagulopathy. STUDY DESIGN: Pregnant New Zealand white rabbits (28th day of pregnancy or normal gestation period of 29-35 days) underwent cesarean delivery, followed by intravenous administration of amniotic fluid (a total of 3.0 mL administered in 4 doses over 9 minutes). Thereafter, uncontrolled postpartum hemorrhage was induced by transecting the right midartery and concomitant vein in the myometrium. After initial bleeding for 5 minutes, rabbits received isovolemic fluid resuscitation through the femoral vein with an equivalent volume of blood loss every 5 minutes for 60 minutes. The transfusion regimens included platelet-rich plasma, platelet-poor plasma, and a bolus administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion (8 rabbits per group). Moreover, 60 minutes after initiation of bleeding, rabbits received surgical hemostasis by ligation of bleeding vessels, except in cases with spontaneous hemostasis. RESULTS: The administration of amniotic fluid caused thrombocytopenia (56±3 × 103/µL) and prolonged both clotting time (before administration: 130.0±3.0 to 171.0±5.0 seconds) and prothrombin time (4.5±0.1 to 4.7±0.1 seconds). After the initial 5-minute bleeding in the rabbits, the mean arterial pressure fell to 43±2 mm Hg. Platelet-poor plasma transfusion alone further prolonged clotting time and prothrombin time at 60 minutes (192.0±10.0 and 5.2±0.1 seconds, respectively) with decreasing mean arterial pressure to <40 mm Hg. By contrast, the administration of H12-ADP-liposomes followed by platelet-poor plasma transfusion reduced the prolonged clotting time (153.0±5.0 seconds) and prothrombin time (4.9±0.1 seconds) similar to platelet-rich plasma transfusion (154.0±11.0 and 4.9±0.1 seconds, respectively) at 60 minutes. These rabbits maintained a mean arterial pressure of >45 mm Hg throughout the experiment. H12-ADP-liposome infusion and platelet-poor plasma transfusion and platelet-rich plasma transfusion yielded spontaneous hemostasis in 4 of 8 rabbits, whereas platelet-poor plasma transfusion did not stop bleeding in any of the rabbits. The total blood loss was 59±17 mL in the H12-ADP-liposomes and platelet-poor plasma group, which was half of that in the platelet-poor plasma group (124±10 mL). CONCLUSION: H12-ADP-liposome infusion may be effective in the initial management of postpartum hemorrhage complicated with amniotic fluid embolism, resulting in mitigation of consumptive coagulopathy.

Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.

α-Actinin4 (ACTN4), an isoform of non-muscular α-actinin, is involved in enhancing cell motility and promoting cancer infiltration and metastasis in various cancers. However, information remains limited regarding the pathological significance of ACTN4 expression in upper urinary tract urothelial carcinomas (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who were treated with nephroureterectomy or partial ureterectomy, and analyzed the expression of the ACTN4 protein and the amplification of ACTN4 using immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed ACTN4 protein overexpression and 25 (15%) showed copy number gain (≥4 copies per cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly correlated with ACTN4 protein overexpression and several adverse clinicopathological factors, including higher pathological T stage, lymphovascular invasion, lymph node metastasis, positive surgical margin, concomitant subtype histology, and non-papillary gross finding. Cox univariate regression analyses revealed that both copy number gain of ACTN4 and ACTN4 protein overexpression were significant risk factors for extraurothelial recurrence and death (each p < 0.0001), but multivariate analysis revealed that only copy number gain of ACTN4 was an independent risk factor for extraurothelial recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, respectively). This is the first study demonstrating the aberrant expression status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic indicator in patients with UUTUC.

Composite pheochromocytoma-ganglioneuroma: a case with two distinct components radiographically.

Composite pheochromocytoma is an extremely rare tumor that comprises a pheochromocytoma and an embryologically related neurogenic tumor, such as ganglioneuroma, ganglioneuroblastoma, neuroblastoma, or peripheral nerve sheath tumor. A 46-year-old male with hypertension, elevated plasma catecholamine levels, and suspected pheochromocytoma presented to the National Defense Medical College Hospital. CT and MRI showed two adjacent masses in the left adrenal gland; one was a 6 cm cephalic lesion and the other was a 1.5 cm caudal lesion. Only the 1.5 cm caudal mass showed uptake on 123I-metaiodobenzylguanisine single photon emission CT/CT. Pheochromocytoma was suspected and a left adrenalectomy was performed. Pathology confirmed that the 6 cm mass was a ganglioneuroma and the 1.5 cm mass a pheochromocytoma, with cellular intermingling at their border. The two masses were diagnosed as a composite pheochromocytoma-ganglioneuroma. This is the first report in which the two components of a composite pheochromocytoma can be clearly distinguished in the pre-operative images. If a patient with clinically suspected pheochromocytoma has different components from a typical pheochromocytoma, composite pheochromocytoma should be considered.

Development of intravascular large B-cell lymphoma during prophylactic antibiotic treatment for anti-interferon-gamma autoantibody syndrome: A case report.

Anti-interferon (IFN)-γ autoantibody-positive syndrome is one of the acquired non-HIV cellular immunodeficiencies, caused by abnormalities in the IFN-γ/interleukin (IL)-12 pathways. It is often diagnosed alongside the onset of disseminated mycobacterium infection, and requires continuous antimycobacterial chemotherapy; however, the detailed pathological mechanisms underlying this syndrome, including its prognosis, are not known. To the best of our knowledge, this is the first reported case of intravascular large B-cell lymphoma complicated by anti-IFN-γ autoantibody syndrome, presented in an 82-year-old woman. The patient had been diagnosed with anti-IFN-γ autoantibody immunodeficiency ten years ago. She had repeated subacute fever of undetermined origin for 13 months that made us suspect infections, such as disseminated mycobacterium disease and other viral and fungal infections, despite receiving prophylactic antimycobacterial chemotherapy with rifampicin and clarithromycin. However, all the screenings performed showed no evidence of infectious diseases; thus, she was finally diagnosed with intravascular large B-cell lymphoma via a random skin biopsy. Unfortunately, the patient debilitated rapidly and died. Evidence supporting a correlation between anti-IFN-γ autoantibody syndrome and carcinogenesis is still lacking, although it is known that patients with anti-IFN-γ autoantibody syndrome are at risk of persistent viral infection-related and T-cell lineage-related carcinogenesis. This case demonstrated that patients with anti-IFN-γ autoantibody syndrome are also at risk of developing B-cell lymphoma, such as intravascular lymphoma. This emphasizes that caution should be paid to increased risk of developing malignancy during the long-term management of anti-IFN-γ autoantibody syndrome with cellular immunodeficiency.

Intraepithelial lymphocytes are indicators of better prognosis in surgically resected endometrioid-type endometrial carcinomas at early and advanced stages.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear. METHODS: Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The "TIL score" was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses. RESULTS: By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low "TIL score" were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low "TIL score" (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low "TIL score", and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68+ or CD163+ TAMs were not correlated with prognosis in any patients. CONCLUSIONS: Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.

Laryngeal schwannoma with extralaryngeal extension mimicking a thyroid tumour.

Objective: A schwannoma is a common benign tumour that can arise anywhere in the body. When it occurs in an unusual location such as the larynx, its differentiation from other tumours can be challenging. Herein, we report a case of a laryngeal schwannoma with extralaryngeal extension that mimicked a thyroid tumour, focusing on its characteristic features on MRI. Methods: A 19-year-old male presented with a mass in the left side of the neck and hoarseness for 2 years. Endoscopy showed a submucosal mass in the laryngeal region. MRI found a well-defined solid mass in the thyroid gland, extending to the larynx through the lower edge of the thyroid cartilage. T 2 weighted MRI showed slightly low signal intensity at the central part of the tumour and high signal intensity at the peripheral part of the tumour. Pre-operative imaging suggested that the tumour originated in the thyroid gland. Left thyroidectomy with tumour excision was performed; the tumour was diagnosed as a laryngeal schwannoma with extralaryngeal extension, compressing the thyroid gland. In retrospect, features such as the dumbbell-shape and known as 'target sign' on T 2 weighted MRI were typical features of schwannoma. Additionally, the tumour's extension pattern was similar to previous reports of laryngeal schwannomas with extralaryngeal extension. Conclusion: A large laryngeal schwannoma may extend outside the larynx with significant compression of the thyroid gland. Understanding the pattern of extension and familiarity with the features on MRI can improve the preoperative diagnosis accuracy.

Chronic lymphocytic leukemia and concurrent seminoma in the same testis.

A 59-year-old man presented with a painless testicular mass and underwent a radical orchiectomy. The resected specimen showed a 5-cm-sized, white-yellow and homogenous solid mass in the testicular parenchyma. Histologically, the central part of the tumor exhibited typical features of seminoma. The peripheral part of the tumor exhibited diffuse infiltration of small, monotonous lymphoid cells involving the tunica albuginea. The monotonous lymphoid cells were immunoreactive for CD20, CD79a, CD5, and CD23, and negative for CD3, CD10, and cyclin D1. Kappa light chain restriction was detected on flow cytometry using the resected specimen. Considering the circulating lymphoid cell count of >5.0×103/µL, we diagnosed the peripheral component of the tumor as an infiltration of chronic lymphocytic leukemia. This extremely rare combination of seminoma and lymphoid neoplasm should be considered in the differential diagnosis of classic seminoma with extensive lymphoid reaction in tumors arising in elderly patients.

Co-expression of mesothelin and CA125/MUC16 is a prognostic factor for breast cancer, especially in luminal-type breast cancer patients.

The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox's multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer.

Expression of L-Type Amino Acid Transporter 1 is a Predictive Biomarker of Intravesical Recurrence in Patients with Non-Muscle Invasive Bladder Cancer.

PURPOSE: L-type amino acid transporter 1 (LAT1), a Na+-independent amino acid transporter, is highly expressed in various cancer types. We evaluated the prognostic value of LAT1 expression in non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We retrospectively reviewed 119 consecutive patients who underwent initial transurethral resection of bladder tumor. Of these, 75 patients with NMIBC were included in this study. Patients were classified into two groups according to the proportion of LAT1-positive cells, as determined by immunohistochemistry. Associations between LAT1 expression and clinicopathological factors were analyzed. Cox multivariate analyses were performed to identify independent predictors of intravesical recurrence (IVR). The LAT1 integrated risk model was compared with the European Organization for Research and Treatment of Cancer (EORTC) risk model to evaluate the predictive ability for IVR based on the c-index. RESULTS: The median follow-up was 37 months. Twenty-eight patients (37.3%) had IVR. LAT1 expression was not correlated with any other clinicopathological factors. Patients with high LAT1 expression had a worse IVR-free survival than that of patients with low LAT1 expression (P = 0.038). Cox multivariate analyses indicated that tumor multiplicity and high LAT1 expression were independent predictors of IVR. The LAT1 integrated risk model had a significantly improved performance over the EORTC model for assessing recurrence risk (c-index: 0.695, improvement: 0.091, P = 0.001). When patients were stratified into three groups according to the score calculated by the LAT1 integrated risk model, the 2-year IVR-free survival rates were 93.3% in patients with 0 points, 66.9% for those with 2 points, and 37.5% for those with 4 points. CONCLUSION: High LAT1 expression was an independent predictor of IVR in patients with NMIBC. The LAT1 integrated risk model had good predictability for IVR.

Prognostic similarity between ovarian mucinous carcinoma with expansile invasion and ovarian mucinous borderline tumor: A retrospective analysis.

ABSTRACT: There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.

MicroRNA-21 expression in cancer cells is an independent biomarker of progression-free survival of endometrioid endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in almost all human cancer types, and it might be a useful clinical biomarker and therapeutic target. However, its precise localization and significance in endometrial carcinoma have not been clarified. This study aimed to examine miR-21 expression in endometrial carcinoma and reveal its clinicopathological importance. We investigated miR-21 expression by in situ hybridization (ISH) using locked nucleic acid (LNA)-modified probes in 230 endometrial carcinoma patients. We evaluated miR-21 expression in cancer cells and stroma separately. High miR-21 expression in cancer cells was significantly associated with higher histological grade and lymph node metastasis. In Kaplan-Meier analysis, high miR-21 expression in cancer cells was significantly associated with poor progression-free survival. In particular, in endometrioid carcinoma, high miR-21 expression in cancer cells was an independent prognostic factor associated with poor progression-free survival, as well as older age and higher International Federation of Gynecology and Obstetrics (FIGO) stage.

Tumor budding in upper urinary tract urothelial carcinoma: a putative prognostic factor for extraurothelial recurrence and overall survival.

Tumor budding, defined as a single cancer cell or clusters of fewer than five cancer cells observed at the tumor invasion front, has been reported to be associated with poor prognosis in various types of cancers. However, limited information regarding the pathological and prognostic significance of tumor budding in upper urinary tract urothelial carcinoma (UUTUC) is available. We investigated 135 consecutive patients with newly diagnosed invasive UUTUCs (73 with renal pelvic cancers and 62 with ureteral cancers) treated with nephroureterectomy or partial ureterectomy between 1999 and 2018 in our hospital. Under a × 200 magnification, tumors with 10 or more budding foci were defined as "high tumor budding". The median follow-up period was 53.6 months. Among the 135 patients, 41 (30%; 16 with renal pelvic cancers and 25 with ureteral cancers) showed high tumor budding. High tumor budding was related to adjuvant chemotherapy status, higher pathological T stage, lymphovascular invasion, lymph node metastasis, tumor location, concomitant variant histology, and non-papillary gross finding. The multivariate Cox analysis revealed that LVI and high tumor budding were independent predictors for extraurothelial recurrence (P = 0.039 and 0.014, hazard ratio = 2.50 and 2.88, respectively), and high tumor budding was an independent predictor for overall survival (P = 0.024, hazard ratio = 2.33). Tumor budding can be easily introduced in clinical practice with no need for immunohistochemical analysis, may be an important clinicopathological factor of UUTUC, and is suggested to be useful as a novel predictive prognostic factor of patients with invasive UUTUC.

Zosteriform skin metastasis caused by retrograde lymphatic migration of metastatic squamous cell lung carcinoma.

BACKGROUND: Zosteriform skin metastasis (ZSM) is rare, and its etiology is not well understood. ZSM is possibly derived from the retrograde movement of cancer cells through the lymphatic vessels during disease development. However, it has been difficult to demonstrate it, as no specific findings have been observed. CASE PRESENTATION: A 68-year-old man presented to our department with neck lymphadenopathy. After detailed examinations, squamous cell lung carcinoma (cT2aN3M1c) was diagnosed. Although cisplatin combined with gemcitabine was administered, his cancerous lymphangiopathy was exacerbated, and ZSM was observed on his right chest. Pembrolizumab was initiated as a second-line chemotherapy; however, the patient died 7 months after the initial presentation. In this case, fluorodeoxyglucose-positron emission tomography indicated the presence of skin metastasis and cancerous lymphangiopathy. Similarly, after performing an autopsy, tumor-cell filled lymph ducts were observed in the right subclavian and the cutaneous lymphatic vessel from the right hilar lymph nodes. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that the localization of ZSM in the cutaneous lymphatics was caused by the retrograde movement of cancer cells through the lymphatic vessels, using radiographical and pathological analysis. In addition, fluorodeoxyglucose-positron emission tomography may help predict skin metastasis induced by cancerous lymphangiopathy.

Membrane mesothelin expression positivity is associated with poor clinical outcome of luminal-type breast cancer.

Mesothelin is expressed in various types of malignant tumors. The present study immunohistochemically investigated mesothelin expression and its clinicopathological significance in each subtype of breast cancer, with special reference to its cellular localization, in particular, membrane mesothelin expression. Using tissue specimens from 482 patients with breast cancer, immunohistochemistry was used to study mesothelin expression and help classify its localization as membrane or cytoplasmic expression. Mesothelin expression was detected in 77 (16.0%) cases and was the highest in triple-negative breast cancer (31/75; 41.3%), followed by human epithelial growth factor receptor type 2 type (6/33, 18.2%) and luminal type (36/374; 9.6%). Among the 482 cases, membrane mesothelin expression was detected in 73 cases and was significantly associated with a negative hormone receptor status, higher Ki-67 labeling index, nuclear grade 3 and a lower relapse-free survival rate. Cytoplasmic mesothelin expression was not significantly associated with a lower relapse-free survival rate (P=0.058). In the 343 cases of luminal type, the membrane mesothelin expression-positive group had significantly worse prognosis than the membrane mesothelin-expression-negative group (P=0.042). There was no significant difference in the relapse-free survival rate according to the membrane mesothelin expression status in the triple-negative type and other types. It was suggested that membrane mesothelin expression in luminal type breast cancer is associated with a lower rate of relapse-free survival.

Comparison between AJCC 8th prognostic stage and UICC anatomical stage in patients with primary breast cancer: a single institutional retrospective study.

BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC) proposed a prognostic stage (PS), which included not only anatomical factors, but also biological factors. We aimed to investigate the clinicopathological significance of the PS and to compare PS and anatomical stage (AS) that has been established by the Union for International Cancer Control (UICC). METHODS: Between 2002 and 2017, 800 patients were included in the study. Patients were classified using pathological UICC AS and pathological AJCC PS. The usefulness of PS in comparison with AS was validated using the Akaike information criterion (AIC) and Harrell concordance index (C-index). RESULTS: A total of 401 (50.1%) patients had pathological AS I, 324 (40.5%) had AS II, and 75 (9.4%) had AS III. Meanwhile, 535 (66.8%) had pathological PS I, 163 (20.4%) had PS II, and 102 (12.8%) had PS III. The number of AS II cases was 1.99-fold higher than that of PS II cases. For each stage, these survival curves were almost similar between AS and PS classification. Therefore, many patients to be classified into stage I and stage III were included in AS II group, while many patients to be classified into stage II were included in AS I group. To trichotomize the survival groups, PS appeared to be more specific than AS, and AIC and C-index confirmed the speculation. CONCLUSION: For the prognostication of primary breast cancer patients, AJCC PS appeared to be able to stratify the cases more appropriately than UICC AS.

Aquaporin 3 Expression in Endometrioid Carcinoma of the Uterine Body Correlated With Early Stage and Lower Grade.

Aquaporins (AQPs) are a family of transmembrane water channel proteins distributed in various human tissues. Recent studies revealed that AQPs play important roles in cancer biology. Few studies have documented the relationship between the prognosis, stage, and histological grade of uterine endometrioid carcinoma, with AQP expression. Hence, the present study aimed to investigate this relationship between uterine endometrioid carcinoma and AQP expression. We retrospectively reviewed records of the patients who underwent surgery for uterine body cancer between 1990 and 2010 at the National Defense Medical College Hospital, Saitama, Japan. In 241 cases of endometrioid carcinoma, we immunohistochemically examined the expression of AQP 1, 2, 3, 4, and 5, and their relationship with clinicopathological parameters and the patients' prognosis. We investigated the relationship between the clinicopathological parameters and AQP3 expression, and found that as the FIGO stage and histological grade progressed, the percentage of AQP3 expression tends to decrease. Furthermore, we analyzed progression-free survival/overall survival (PFS/OS) using the log-rank test, and found that the AQP3-positive group had a better prognosis than AQP3-negative group (PFS: P < 0.001, OS: P = 0.002, respectively). Using Cox's univariate proportional hazard model, we revealed that AQP3 had a low hazard ratio. However, according to Cox's multivariate proportional hazard model, AQP3 was not an independent prognostic factor. Among the endometrioid carcinoma patients, the AQP3-positive group was associated with early stage and lower grade compared to the AQP3-negative group. Therefore, AQP3 has the potential to serve as a predictor of prognosis, although further investigation is necessary to elucidate the biological mechanism of AQP3 in endometrioid carcinoma.

Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus.

The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in cancer cell growth and survival. To determine the significance of LAT1 in the prognosis of endometrial endometrioid carcinoma, we investigated LAT1 expression in 353 endometrioid carcinoma patients by immunohistochemical analysis using tissue microarray. The tumors in which stained tumor cells made up more than 25% of the tumor were graded as high expression. High expression of LAT1 was detected in 29 (8.2%) of patients. The ratio of high LAT1 expression did not significantly differ by age (< 60 vs. ≥ 60), FIGO stage (stage I/II vs. III/IV), histological grade (grade 1 vs. grade 2/3), or lymph node metastasis (positive vs. negative). However, high LAT1 expression in endometrioid carcinoma was associated with a poorer progression-free survival and overall survival, as per the results of the log-rank test (P = 0.0263 and 0.0404, respectively). Cox univariate and multivariate analyses revealed that high LAT1 expression is an independent marker of poor progression-free survival (hazard ratio = 2.598, P = 0.0137), in addition to a higher age (≥ 60 years vs. < 60 years), FIGO stage (stage III/IV vs. I/II), and histological grade (grade 2/3 vs. grade 1). In conclusion, we demonstrate that LAT1 is associated with a poor prognosis of endometrioid carcinoma of the uterine corpus.

Different Prognostic Implications of Aquaporin-1 and Aquaporin-5 Expression among Different Histological Types of Ovarian Carcinoma.

The aquaporins (AQPs) are a family of transmembrane water channel proteins that are distributed in various human tissues. Recent studies have suggested that AQP expression correlates with various aspects of cancer biology that determine the aggressiveness of different cancers. Ovarian carcinoma is one of the most lethal gynecological cancers. Some studies have suggested that AQPs are expressed in ovarian carcinoma, and are associated with cancer cell growth and migration. In this study, we immunohistochemically evaluated the expression of AQP1, 3, 5, and 9 in a total of 300 ovarian carcinomas using tissue microarrays. In our analyses of correlations between aquaporin expression and overall survival, high AQP5 expression was significantly associated with poorer prognosis (P = 0.029). For AQP1, the low expression group trended towards poorer prognosis than the high expression group, but the difference was not statistically significant. When ovarian carcinomas were divided by histological types, high AQP5 expression correlated with poorer prognosis in serous carcinoma (P = 0.015), and low AQP1 expression correlated with poorer prognosis in clear cell carcinomas (P = 0.0055). By contrast, high AQP1 expression correlated with poorer prognosis in mucinous carcinoma (P = 0.0001) and endometrioid carcinoma (P = 0.021). Our studies suggest that AQPs can be useful prognostic markers in ovarian carcinoma, but their correlation with prognosis depends on the histological type of ovarian carcinoma.

Fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca: an autopsy case report.

CASE: We describe a rare case of antibiotic-associated fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca. A 79-year-old man with a history of antibiotic therapy was admitted to our emergency department, complaining of consciousness disturbance. Initially, we suspected septic shock and diabetic ketoacidosis caused by intestinal infection. Although we administered sufficient extracellular fluid, his blood pressure was not elevated and his abdomen gradually swelled. OUTCOME: The patient died of shock and abdominal compartment syndrome. Autopsy revealed widespread jejunal necrosis in conjunction with colitis, suggesting fulminant pseudomembranous enterocolitis caused by K. oxytoca infection. CONCLUSION: As the clinical features of pseudomembranous enterocolitis caused by K. oxytoca resemble the features of colitis caused by Clostridium difficile, conservative therapy is applied first. However, fulminant pseudomembranous enterocolitis is a lethal disease, necessitating early operation for resection of the necrotic lesion. This report highlights the need for better surgical criteria at an early stage.

Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma.

L-type amino acid transporter 1 (LAT1) is a Na+-independent neutral amino acid transporter that plays a key role in cancer cell growth and survival. To determine the significance of LAT1 in prognosis and resistance to chemotherapy in ovarian carcinoma, we investigated the LAT1 expression in 245 ovarian carcinoma patients by immunohistochemistry using tissue microarray. High expression of LAT1 was detected in 85 (34.7%) patients. The ratio of high expression of LAT1 was significantly high in clear cell carcinoma and low in serous carcinoma compared to other histological types (P < 0.0001). High expression of LAT1 in ovarian carcinoma was associated with poorer prognosis as per log-rank test (P = 0.008). Cox's univariate and multivariate analysis revealed that high expression of LAT1 is an independent marker indicating poor prognosis (hazard ratio = 2.810, P < 0.0001) as well as the FIGO stage III/IV (vs. I/II) and suboptimal surgery. High LAT1 expression was also found to be associated with resistance to chemotherapy (P = 0.016) notably in clear cell carcinoma. In conclusion, we demonstrate that LAT1 is not only associated with poor prognosis of ovarian carcinoma, but also associated with chemoresistance in ovarian carcinoma.