Clonal Origin and Lineage Ambiguity in Mixed Neuroendocrine Carcinoma of the Uterine Cervix.

Small-cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. This study established a panel of organoid lines from patients with SCNEC of the cervix and ultimately focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. Tracking single cells indicated the existence of cells with bipotential differentiation toward SCNEC and adenocarcinomas. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for keratin 19 expression, changes in the differentiation of each cell were shown to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state.

Dedifferentiation of neuroendocrine carcinoma of the uterine cervix in hypoxia.

Neuroendocrine carcinoma of small cell type (SCNEC) is a rare pathological subtype in cervical cancer, which has a worse prognosis than other histological cell types. Due to its low incidence and the lack of experimental platforms, the molecular characteristics of SCNEC in the cervix remain largely unknown. Using the cancer tissue-originated spheroid (CTOS) method-an ex vivo 3D culture system that preserves the differentiation status of the original tumors-we established a panel of CTOS lines of SCNEC. We demonstrated that xenograft tumors and CTOSs, respectively, exhibited substantial intra-tumor and intra-CTOS variation in the expression levels of chromogranin A (CHGA), a neuroendocrine tumor marker. Since hypoxia affects differentiation in various tumors and in stem cells, we also investigated how hypoxia affected neuroendocrine differentiation of SCNEC of the uterine cervix. In the CTOS line cerv21, hypoxia suppressed expression of the neuroendocrine markers CHGA and synaptophysin (SYP). Flow cytometry analysis using CD99 (a membrane protein marker of SCNEC) revealed decreased CD99 expression in a subset of cells under hypoxic conditions. These expression changes were attenuated by HIF-1α knockdown, and by a Notch inhibitor, suggesting that these molecules played a role in the regulation of neuroendocrine differentiation. The examined SCNEC markers were suppressed under hypoxia in multiple CTOS lines. Overall, our present results indicated that neuroendocrine differentiation in SCNEC of the uterus is a variable phenotype, and that hypoxia may be one of the factors regulating the differentiation status.

The efficacy of surgical treatment of recurrent or persistent cervical cancer that develops in a previously irradiated field: a monoinstitutional experience.

BACKGROUND: There are no guidelines about the selection of recurrent cervical cancer patients for salvage surgery. METHODS: Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery (the surgery group) or palliative care alone (the palliative group) were identified. Patient characteristics, treatment-related complications, and survival were retrospectively compared between the two groups. RESULTS: A total of 79 patients (surgery group, n = 51; palliative group, n = 28) were identified. In the surgery group, no intraoperative complications or treatment-related deaths occurred. Eleven patients (21.6%) experienced severe postoperative complications. After a median follow-up period of 41.5 months, 23 patients (45.1%) had developed recurrent disease, predominantly at distant sites, and 19 patients (37.3%) had died of disease progression. The estimated 3-year progression-free survival (PFS) and overall survival rates of the surgery group were 50.4 and 56.5%, respectively. In the palliative group, all of the patients died of disease progression. Positive surgical margins and lymph node metastasis were found to be independent prognostic factors for PFS in the surgery group. Among the patients with no or one poor prognostic factor, the patients in the surgery group survived significantly longer than those in the palliative group. However, among the patients with 2 poor prognostic factors, the surgery group and palliative group displayed similar survival periods. CONCLUSIONS: Salvage surgery is a curative treatment in recurrent or persistent cervical cancer patients. However, considering its high surgical complication rate, salvage surgery should only be offered to carefully selected patients.

Cervical varix complicated by placenta previa: A case report and literature review.

Uterine cervical varix is rare, and its clinical course is poorly understood. Therefore, we present a case report of cervical varix complicating placenta previa before describing our findings in the context of an electronic database search of relevant reports. In the case report, we describe the clinical course and imaging results of a 35-year-old woman who was diagnosed with cervical varix complicated by placenta previa. Investigation by magnetic resonance imaging, serial ultrasonography, and speculum confirmed the diagnosis, and a healthy baby was successfully delivered at 36 weeks of gestation by cesarean section. An electronic search identified nine previous cases of cervical varix complicated by placenta previa in the literature. Clinicians should be aware of cervical varices when managing placenta previa to avoid iatrogenic rupture or misdiagnosis of placenta accreta by magnetic resonance imaging.

Small microplastic ingestion by the calanoid Centropages furcatus in the Gulf of Thailand.

Microplastics could be ingested by many organisms, including zooplankton, involving bioaccumulation and biomagnification mechanisms a cross food webs. The information about microplastic ingestion by zooplankton keeps increasing worldwide. However, it is still limited for particle sizes under 300 µm (small microplastics, SMPs) and in areas such as Southeast Asia, which is considered one of the hotspots for plastic debris. This study aimed to characterize the size, shape, and polymer types of the SMPs ingested by the copepod Centropages furcatus in Si Chang Island (upper Gulf of Thailand). The study spans offshore and coastal waters, with data collected across wet, intermediate, and dry seasons. Using a semi-automated technique for micro-FTIR (Fourier-transform infrared) scanning spectroscopy for particle analysis, we found ingested SMPs in all samples. A total of 750 individuals of the calanoid Centropages furcatus were analyzed, finding 309 plastic particles and an average ingestion value of 0.41 ± 0.13 particles ind-1, one of the highest recorded values. All the particles were fragments, with a predominant size under 50 µm, and polymer types as Polypropylene (PP, 71 %), followed by Ethylene-Propylene-Diene-Monomer (EPDM, 16 %) and Polyethylene (PE, 7 %). Up to 470.2 particles m-3 were estimated to be retained by this calanoid species and potentially available for trophic transfer. The effect of rainfall on SMPs ingestion was inconclusive, with a non-significant observed tendency to higher ingestion values near the coastal area than offshore area, suggesting a decrease in particle exposure due to the runoff effect. Nevertheless, future studies should increase the frequency of surveys to arrive at better conclusions.

Microplastics on plankton samples: Multiple digestion techniques assessment based on weight, size, and FTIR spectroscopy analyses.

Digestion protocols are needed to determine microplastics abundance and features. This study assessed the organic matter (OM) digestion efficiency on plankton samples and the MPs' weight, size, and polymer changes under different digestion techniques. For this, 2-step (KOH and H2O2 + Fe2+) and 3-step (2-step and enzymes) digestion techniques were assessed under different duration and temperature conditions. The results obtained for OM digestion with 2-step and 3-step techniques were satisfactory. Weight changes were registered for polyethylene terephthalate (PET), polystyrene foam, polyvinyl chloride, and polycarbonate with 2-step digestion, but with inconsistent values. Significant size changes were registered only for PET applying 2-step digestion techniques at 60 °C. Using 40 °C for 72 h prevailed all polymers from size changes. Polyethylene weathered MPs were also preserved, including an enzymatic step. Polymer fingerprints were not affected by any digestion technique. Based on these results, any method applying high temperatures will damage MPs.

Heterogenous chemosensitivity of a panel of organoid lines derived from small cell neuroendocrine carcinoma of the uterine cervix.

Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare disease with a poor prognosis. The lack of established disease models has hampered therapy development. We generated a panel of cancer tissue-originated spheroid (CTOS) lines derived from SCNEC of the uterine cervix using a method based upon cell-cell contact throughout the preparation and culturing processes. Using 11 CTOS lines, we assessed the sensitivity of various drugs used in clinical practice. Drug sensitivity assays revealed significant heterogeneous inter-CTOS chemosensitivity. Microarray analyses were then performed to identify sensitivity-related gene signatures. Specific gene sets were identified which likely contribute to the sensitivity to the tested drugs. We identified a line (Cerv54) that was exceptionally sensitive to irinotecan. Cerv54 had increased levels of CES1, which catalyzes the conversion of irinotecan to the active form, SN38, although in Cerv54 cells, SN38 was undetectable, CES1 expression and activity were markedly low compared to the liver, and a CES1 inhibitor had no effect on irinotecan sensitivity. These results suggested a novel irinotecan mode of action in Cerv54. Our CTOS lines may be useful for understanding the variation and mechanism of drug sensitivity, contributing to the understanding and development of chemotherapeutic drugs.

Obstetric outcomes and acceptance of alternative therapies to blood transfusion by Jehovah's Witnesses in Japan: a single-center study.

We sought to investigate obstetric outcomes and acceptance rates for blood products or types of autotransfusion by Jehovah's Witnesses (JWs) at a single institution in Japan. We retrospectively reviewed cases of 84 pregnant JW patients and 95 deliveries from April 2001 to August 2017. We examined the acceptance rates of blood transfusions, blood products, and autotransfusion types in patients who experienced postpartum hemorrhage (PPH), and investigated estimated hemorrhage volume at delivery and PPH treatments. Of the 84 JW patients, none accepted blood transfusion; however, 75 patients (89.3%) accepted blood products, 57 (67.9%) accepted autotransfusion using intraoperative cell salvage, and four (4.8%) refused all alternatives to blood transfusion. Furthermore, PPH > 1000 mL occurred in 18 of the 95 (18.9%) deliveries. Of these 18 patients, four (22.2%) required blood products and three (16.7%) required supracervical hysterectomy to control PPH. No maternal deaths occurred. Approximately 95% of the patients observed accepted all or some alternatives to blood transfusion. To treat JW patients in a safer manner, understanding their individual acceptance of alternatives to blood transfusion is important for the strategic use of such alternatives.

[Examination of local alliances in clinical path (home parenteral nutrition)].

In revising compensation for medical treatment, shifts in home care systems such as management of lifestyle-related diseases, management of a patient within reach of a daily medical treatment, and an attempt to curtail hospitalization are suggested as concrete means of planning medical expenses to be appropriate. In doing this, it is getting more important that the medical institution pursue its purpose and must select the course of treatment and to solidify a medical cooperation among the institutions because a medical treatment is often not concluded at only one medical institution. Although a revision of compensation for medical treatment is getting more difficult due to three consecutive negative revisions in the past, a new clinical path for a local solidarity of femoral neck fracture has been found. Because of this revision, we think that it is necessary to make a system able to shift medical treatment and to care from hospital to facilities in the district and at home. We studied the clinical path in order to develop an effective and solidified cooperation with people of the district with regard to home parenteral nutrition, which is the most frequent medical treatment in case of a home care shift from that of our hospital's support for patients leaving the hospital.

Placenta accreta following hysteroscopic myomectomy.

Hardly any report exists on the influence of hysteroscopic myomectomy on subsequent pregnancy. Placenta accreta is most often associated with placenta previa in women with multiple prior cesarean sections. We report the first case of placenta accreta without placenta previa during the first pregnancy subsequent to hysteroscopic myomectomy.