Lymph Node Metastasis and Patterns of Recurrence in Vulvar Carcinoma: 10 Years' Single Center Experience.

Vulvar carcinoma is a relatively rare malignancy and there is a paucity of data, especially from India and other developing countries regarding the prognostic factors impacting recurrence and survival. A retrospective observational study was conducted in the Department of Gynecologic Oncology at a tertiary care, regional cancer institute, including all patients with carcinoma vulva who underwent surgery between 2009 and 2018. Demographic profile, surgical-pathological information, details of neo-adjuvant chemotherapy, adjuvant radiation and chemotherapy, and peri-operative complications were analyzed. Long-term follow-up data was gathered, with an evaluation of various prognostic factors impacting recurrence and overall survival outcome. Forty-five cases with mean age of 56.2 years (range 29-82) were treated during the study period. Surgery was the initial treatment modality in 41 (91.1%) cases. Neo-adjuvant chemotherapy prior to surgery was given to four cases. After complete surgico-pathological staging, most patients had stage I disease (26 cases, 57.8%) and 22.2% had stage II disease. Owing to microscopic lymph node involvement, seven cases (15.6%) belonged to FIGO stage III disease. Two cases had stage IVA disease with fixed groin nodes. Adjuvant chemotherapy in the form of 5-fluoro uracil and cisplatin was administered to four out of the nine patients with nodal involvement. The remaining five were advised adjuvant groin radiation. At a median follow-up of 34 months (range 2-114 months), 12 cases (26.7%) experienced a recurrence and one case with stage IVA disease progressed during adjuvant chemotherapy. The 5-year overall survival was 76.6% and the 5-year disease-free survival was 69.6%. There were a total number of 10 deaths, of which seven were due to disease recurrence or progression and the remaining 30% of deaths were due to medical co-morbid conditions. Overall survival was negatively impacted by increasing age (age > 60 years), number of positive nodes, presence of perinodal spread, and stage of the disease. Recurrence-free survival was significantly reduced in those with the presence of peri-nodal spread and lympho-vascular space invasion. The incidence of lymph node metastasis was found to be higher in patients with age > 60 years, increasing tumor size, presence of lympho-vascular space invasion and the number of lymph nodes removed. In carcinoma vulva, treatment should be individualized with multidisciplinary cooperation. In our series, we found that the stage of disease, nodal positivity, and nodal positivity with extra-capsular spread were significant prognostic factors impacting survival on analysis. Lymph nodal positivity was associated with increasing tumour size, presence of lympho-vascular invasion, and patient age.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

Phase II Trial on the Feasibility of Single-Dose Intraoperative Intraperitoneal Carboplatin in Advanced Epithelial Ovarian Cancer Following Optimal Cytoreductive Surgery.

To evaluate the feasibility administering single-dose intraoperative intraperitoneal carboplatin (IP) in advanced epithelial ovarian cancer (EOC) after optimal primary or interval debulking surgery. A phase II non-randomized prospective study conducted at a regional cancer institute from January 2015 to December 2019. The advanced high-grade epithelial ovarian cancer FIGO stage IIIB-IVA was included. A total of 86 consented patients with optimal primary and interval cytoreductive surgeries received single-dose intraoperative IP carboplatin. The immediate (< 6 h), early (6-48 h), and late (48 h-21 days) perioperative complications were recorded and analyzed. The severity of adverse events was graded on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). A total of 86 patients received single-dose intra-operative IP carboplatin during the study period. The 12 (14%) patients underwent primary debulking surgery and 74(86%) interval debulking surgery (IDS). The 13 (15.1%) patients underwent laparoscopic/robotic IDS. All the patients tolerated the intraperitoneal carboplatin well with no or minimal adverse events. Three cases (3.5%) needed resuturing for the burst abdomen, three cases (3.5%) had paralytic ileus for 3-4 days, one case (1.2%) underwent re-explorative laparotomy for hemorrhage, and one case (1.2%) mortality due to due late sepsis. The 84 (97.7%) of 86 cases received scheduled IV chemotherapy on time. Single-dose intraoperative IP carboplatin is a feasible procedure with no or minimal manageable morbidity. The procedure is user friendly combining the prognostic benefits of IP chemotherapy with assurance of earliest timely administration of chemotherapy in advanced EOC. Our study is a hypothesis generating for the future clinical trials comparing single-dose NIPEC versus HIPEC in advanced EOC.

Clinico-Pathological Characteristics, Management, and Prognostic Factors of Patients with Uterine Carcinosarcoma: a Retrospective Analysis.

Uterine carcinosarcoma is a rare, highly aggressive, rapidly progressing neoplasm associated with a poor prognosis. It comprises 1-5% of all uterine malignancies but accounts for 16.4% of all deaths caused by uterine malignancies. There is a definite paucity of data available from the Indian subcontinent. Hence, we retrospectively conducted this study to analyze the clinical and pathological characteristics and outcomes of women with uterine carcinosarcoma in the past 10 years managed at the tertiary care center. This is a retrospective study of women with histologically proven uterine carcinosarcoma treated at a tertiary cancer center in South India between August 2009 and April 2019. Inpatient and outpatient records were reviewed; clinicopathological data were collected; and follow-up and survival data were ascertained. Over a period of 10 years, 20 patients were diagnosed with uterine carcinosarcoma. The majority of patients were postmenopausal (80%). Post-menopausal bleeding was the main presenting complaint in about 80% of patients. More than two-thirds of patients presented in the early stage (stage I, 55%; stage II, 20%). All patients underwent staging laparotomy. Patients with good performance status (85%) received adjuvant concurrent chemoradiotherapy and chemotherapy. At a median follow-up of 40 months, 7 (35%) patients were alive, out of which 6 are disease-free and 1 had a recurrence. The event-free survival at a median follow-up of 40 months was 40% and the overall survival was 48.5%. The outcome did not significantly differ based on the age, tumor histology (heterologous versus homologous), stage, and depth of myometrial invasion. Uterine carcinosarcoma, though rare, needs to be recognized as a distinct entity, and treated aggressively. Surgery is the cornerstone of therapy. Adjuvant concurrent chemoradiation and chemotherapy improve local control and may delay recurrence, but have shown little survival advantage. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on this tumor.

Outcomes of Cancer Surgery During the COVID-19 Pandemic: Preparedness to Practising Continuous Cancer Care.

The COVID-19 pandemic has placed unprecedented pressure on healthcare services. Deprioritisation of nonemergency clinical services and growing concerns of adverse outcomes of COVID-19 in cancer patients is having a deleterious impact across oncologic practice. We report cancer surgery outcomes taking into account the acuity of the COVID-19 situation. A prospectively maintained database of the Department of Surgical Oncology was analysed from 1st May to 30th June, 2020, to evaluate the perioperative outcomes, morbidity and mortality following major surgical procedures. A total of 359, preoperatively, tested negative for COVID-19 underwent surgery. Median age was 52 years with 26.7% (n = 96) above the age of 60 years. Sixty-one percent (n = 219) patients were American Society of Anaesthesiology grades II-III. As per surgical complexity grading, 36.8% (n = 132) cases were lower grades (I-III) and 63.2% (n = 227) were complex surgeries (IV-VI). 5.3% (n = 19) had ≥ grade III Clavien-Dindo complication, and the postoperative mortality rate was 0.27% (n = 1). Major complication rates in patients > 60 years were 9.3% in comparison to 4.1% in < 60 years (p = 0·63). The median hospital stay was 1-10 days across subspecialties. Postoperatively, repeat COVID 19 testing in 2 suspected patients were negative. Our study showed that after screening, triaging and prioritisation, asymptomatic cases may undergo cancer surgeries without increased morbidity during COVID-19 pandemic.

Impact of Optimal Therapy and Prognostic Factors in Malignant Germ Cell Tumors of Ovary: 20 Years' Institutional Experience.

The objective of this study is to analyze the impact of clinicopathological and treatment-related factors on survival in patients with malignant ovarian germ cell tumor. A total of 253 patients of ovarian germ cell malignancy were retrospectively reviewed during 2000-2019. Out of these, 111 had primary treatment at our institute, which is a dedicated regional cancer center. The remaining 142 were operated elsewhere and were referred to us for adjuvant chemotherapy or with recurrent disease. The clinicopathological and treatment-related characteristics were analyzed for association with tumor persistence/recurrence or death. Among them, 107 were dysgerminomas; 60 had endodermal sinus tumor, 53 mixed germ cell tumors, and 31 immature teratoma; and one each had embryoma and primitive germ cell tumor. The median follow-up period was 19 months (range 0-214). Median time to recurrence or progression was 5 months. Forty-nine patients (19.4%) had a recurrence and there were 16 (6.3%) deaths. Five-year disease-free-survival was 71.3% and 5-year overall survival rate was 88.1%, for the entire cohort. Disease-free-survival was 90.4% and overall survival was 92.1% for patients entirely treated at the reporting institute. Sub-group analysis based on treatment adequacy showed that survival rate was 91.0% in patients who had timely and complete initial treatment versus 78.3% in patients where treatment was incomplete or delayed (p = 0.032). Factors affecting relapse were tumor histology, absence of surgical staging, presence of residual disease, inadequate response to chemotherapy, treatment outside reporting institute, and incomplete/delayed chemotherapy. Significant factors adversely affecting survival were presence of post-operative residual disease, tumor histology, incomplete response to chemotherapy, and inadequate/delayed treatment at primary setting. There was no statistically significant difference based on disease stage and whether fertility-sparing surgery or non-fertility-sparing surgery was performed. Prognosis of ovarian germ cell malignancies is excellent with timely, optimal treatment. The outcome improves significantly if managed adequately in the primary setting, involving dedicated gynecologic oncologists.

Metabolic Reprogramming and Lipophagy Mediates Survival of Ascites Derived Metastatic Ovarian Cancer Cells.

OBJECTIVE: The study was aimed at understanding the survival of metastatic ovarian cancer spheroids in the malignant ascites microenvironment. METHODS: All the assays were performed using aseptically collected patient samples. The cells were characterized for the expression of ovarian and cancer stem cell markers using immunocytochemistry. The presence of lipid in the primary metastatic cancer spheroids were confirmed by neutral fat staining using Oil Red-O and transmission electron microscopy. The mRNA expression of autophagy and lipid metabolism genes was analyzed using RT-PCR. The lipid content was analyzed using lipidomics analysis. Etomoxir and chloroquine were used to study the effect of inhibition of autophagy in the metastatic cells. The data were analyzed using appropriate statistical tools and a p-value <0.05 was considered to be statistically significant. RESULTS: Metastatic ovarian cancer spheroids exhibit cancer stem like properties and undergo a metabolic reprogramming when they disseminate from the primary tumor. We report here the accumulation of numerous cytoplasmic lipid droplets and lipophagic vesicles in the metastatic cells in contrast to their primary tumors. In addition we also report that these cells depend on lipophagy for the utilization of lipids rather than the conventional lipolytic pathway. The lipidomics analysis data reveals that the metastatic cells possess high levels of unsaturated fatty acids. We have also reported the occurrence of distinct accumulation of multiple nuclei in the patient derived metastatic cells. Inhibition of beta-oxidation and autophagic machinery using etomoxir and chloroquine resulted in cell death suggesting a potential mode to suppress metastatic cancer cells. CONCLUSION: Metabolic reprogramming is a characteristic feature of the metastatic ovarian cancer cells that are persisting in the malignant ascites. Targeting of the metastatic by gaining an insight into the various metabolic and molecular changes that occur in the metastatic niche provides a promising therapeutic approach in management of the disease.

Low-grade Neuroendocrine Tumor of the Cervix: Report of 3 Cases of a Rare Neoplasm With Review of the Literature.

Neuroendocrine neoplasms are uncommon in the cervix with almost all representing neuroendocrine carcinomas (NECs), either small cell or large cell type. Cervical low-grade neuroendocrine tumors (NETs) are extremely rare with few recent reports using contemporary modern diagnostic criteria. We report 3 cases of cervical NET in patients aged 32 to 57 yr and undertake a review of the literature. The first case was a pure grade 2 NET with pelvic lymph node metastasis (FIGO stage IIIC1). In the second case, a grade 1 NET was associated with high-grade squamous intraepithelial lesion, adenocarcinoma in situ and human papillomavirus (HPV)-associated adenocarcinoma and was FIGO stage IA1. The third patient underwent chemoradiotherapy following a biopsy diagnosis of a high-grade NEC which was radiologically FIGO stage IIIC1 and salvage hysterectomy revealed residual tumor with features of a grade 1 NET. In all cases, the NET was diffusely positive with at least 2 of the neuroendocrine markers chromogranin, synaptophysin, and CD56. The first tumor was p16 negative and the third exhibited block-type immunoreactivity. Molecular tests revealed high risk HPV types 18 and 51 in the third case but no HPV in the first case. p16 immunohistochemistry and HPV molecular testing was not available in the second case. The patients remain disease free with follow-up ranging from 2 to 8 yr. Since a combination of NET and NEC is extremely rare at all sites due to a different pathogenesis, we speculate that in the third case, the NET developed out of the NEC as a "maturation" phenomenon secondary to chemoradiotherapy.

Role of Salvage Surgery in Gestational Trophoblastic Neoplasia: a Regional Cancer Centre Experience.

Gestational trophoblastic neoplasia (GTN) is a curable cancer with chemotherapy. However, some develop chemoresistance to standard chemotherapy and surgery can be a useful option in them. Our study aimed to assess the role of salvage surgery in GTN with chemoresistance. It is a retrospective hospital-based study from 2000 to 2021. Case sheets of women who underwent salvage surgery for chemoresistance were reviewed and clinical parameters like preoperative hCG, antecedent pregnancy, WHO risk score, multiple chemotherapy regimens prior surgery, presence of > 1 disease site, and presence of residual choriocarcinoma that predicted the effect of surgery on serological response were assessed using Fisher's exact test. A total of 19 patients with high-risk GTN developed chemoresistance and underwent salvage surgery. Eight underwent hysterectomy, 3 underwent hysterectomy plus adnexal tumour resection, six received fertility-sparing surgery, and two underwent segmental resection of the lung. Histopathological examination revealed viable tumour in 7/19 patients, but significant fall in median hCG level from 161.5 mIU/ml (preoperatively) to 15.5 mIU/ml (postoperatively) was noted. Preoperative hCG < 100 mIU/ml (p = 0.019) was the most important determinant of complete response to surgery. All the patients who had disease confined to the uterus and/or lungs at the time of surgery achieved remission after completion of treatment. Our study concludes that in the case of chemoresistant high-risk GTN, carefully selected cases with low hCG levels and disease confined to the uterus and/or lungs get the most benefit of surgery. The use of postoperative chemotherapy after complete response is essential to maintain remission and prevent relapse.

Low-Grade Serous Ovarian Carcinoma: a Retrospective Study from a Tertiary Cancer Institute.

The aim of this study was to evaluate the clinico-pathological behaviour and treatment patterns of low-grade serous carcinomas (LGSC) of ovary treated at a regional cancer centre. A retrospective analysis was done for the histopathology-proven cases of low-grade serous ovarian carcinoma, treated at a tertiary cancer institute between January, 2010, and September, 2019. There were 28 patients identified from the medical records with low-grade serous ovarian carcinoma. Median age of the patients was 43 years [22-79 years]. Average BMI was 22.3 ± 4.0 kg/m2 [range 15.2-31.2]. Twenty-one (75%) were parous and 7 (25%) were non-parous women. Median CA125 level was 188 IU/ml [range 6-14,187 IU/ml]. Ten (35.7%) patients had primary surgery elsewhere and 8 (80%) out of these patients had to undergo repeat staging. Fertility sparing surgery (FSS) was offered to 4 (14.3%) patients. Five (17.8%) patients had received neoadjuvant chemotherapy for advanced disease and poor performance status. Almost 82.2% (23) of the patients had no macroscopic residual disease at the primary surgery. According to International Federation of Obstetrics and Gynaecologists (FIGO) stage for ovarian carcinoma, there were 7 (25%), 6 (21.4%), 13 (46.4%), and 2 (7.1%) patients in the stages I, II, III, and IV respectively. Post-operative adjuvant chemotherapy was offered to 7 (25%), hormonal therapy (anastrozole/tamoxifen) to 7 (25%), and rest of 14 (50%) patients were under surveillance. Median follow-up time for the study group was 36 months. Overall survival (OS) and disease-free survival (DFS) at 2 years was 96.4% and 89.1%, respectively. Low-grade serous carcinomas of ovary differ biologically from high-grade serous ovarian carcinoma. Surgery is the cornerstone of the treatment. Further research is needed to understand the behaviour of these tumours for effective treatment strategies in future.

Growing Teratoma Syndrome a Rare Clinical Entity: Two Decades Management Experience from the Regional Cancer Institute.

To study the clinical, biochemical, radiological, pathological characteristics, surgical treatment details, and follow-up of growing teratoma syndrome (GTS) patients. This is a retrospective study of GTS treated in the Department of Gynaecological Oncology at a regional cancer institute from March 2000 to March 2020. A total of 303 cases of germ cell ovarian cancers were treated, and 8 (2.6%) of 303 cases recurred as GTS during this period. The patients presenting with recurrent GTS were studied for clinical, radiological, tumor markers, surgical management, histopathology, and post-operative follow-up details that were analyzed retrospectively. The Kaplan-Meier curve was used for the survival analysis. The 8 out of 303 cases of germ cell ovarian cancers recurred as GTS and the incidence rate is 2.6% during this period. In the six (75%) of eight cases, the histopathology report was immature teratoma ovaries. The five cases (62.5%) were in advanced stage. All the eight recurrent GTS cases received optimal surgical cytoreduction. The overall disease-free survival is 85.7% and one patient has recurrence after the surgery for GTS at 23rd month of follow-up visit. All the patients are alive till date. The GTS represents a rare clinical and pathological phenomenon. Nevertheless, GTS should be considered as one of the differential diagnosis in young patients having normal tumor markers with recurrent carcinomatosis following the primary treatment germ cell tumors of ovaries. The optimal cytoreduction of recurrent GTS leads to prolonged survival and possible cure in young patients.

A Prospective Study on Metronomic Scheduling of Non-chemotherapeutic Drugs in Advanced Epithelial Ovarian Cancers.

The objectives of this study are to assess the role of non-chemotherapeutic combination of drugs as maintenance therapy, after standard treatment, for advanced epithelial ovarian cancers (EOC) and to determine the recurrence-free survival (RFS) and cancer-specific survival (CSS). One hundred women with advanced high-grade EOC who had completed standard treatment by primary/interval debulking surgery followed by adjuvant chemotherapy were randomised to either receive (study group) or not to receive (control group) the non-chemotherapeutic maintenance therapy (oral metformin, anastrozole, aspirin, atorvastatin, vitamin D, injection zoledronic acid). Both groups were followed up, and trends of RFS and CSS were analysed. One hundred patients were analysed. Median RFS was 18 months (95% CI: 13-24) in study group versus 16 (95% CI: 14-20) in the control group (P value = 0.57). Median CSS in the study group was lesser than that in the control group (47 months (95% CI: 31-68) versus 51 (95% CI: 32-66), P value = 0.76). Five-year CSS was not significantly different between the groups (47% study vs 40% control, P value = 0.51). The use of combination of non-chemotherapeutic drugs as maintenance therapy was found to have no significant impact on the survival or reduction of recurrences in patients with advanced epithelial ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01261-w.

PHO1 family members transport phosphate from infected nodule cells to bacteroids in Medicago truncatula.

Legumes play an important role in the soil nitrogen availability via symbiotic nitrogen fixation (SNF). Phosphate (Pi) deficiency severely impacts SNF because of the high Pi requirement of symbiosis. Whereas PHT1 transporters are involved in Pi uptake into nodules, it is unknown how Pi is transferred from the plant infected cells to nitrogen-fixing bacteroids. We hypothesized that Medicago truncatula genes homologous to Arabidopsis PHO1, encoding a vascular apoplastic Pi exporter, are involved in Pi transfer to bacteroids. Among the seven MtPHO1 genes present in M. truncatula, we found that two genes, namely MtPHO1.1 and MtPHO1.2, were broadly expressed across the various nodule zones in addition to the root vascular system. Expressions of MtPHO1.1 and MtPHO1.2 in Nicotiana benthamiana mediated specific Pi export. Plants with nodule-specific downregulation of both MtPHO1.1 and MtPHO1.2 were generated by RNA interference (RNAi) to examine their roles in nodule Pi homeostasis. Nodules of RNAi plants had lower Pi content and a three-fold reduction in SNF, resulting in reduced shoot growth. Whereas the rate of 33Pi uptake into nodules of RNAi plants was similar to control, transfer of 33Pi from nodule cells into bacteroids was reduced and bacteroids activated their Pi-deficiency response. Our results implicate plant MtPHO1 genes in bacteroid Pi homeostasis and SNF via the transfer of Pi from nodule infected cells to bacteroids.

Cytotoxicity and hemostatic activity of chitosan/carrageenan composite wound healing dressing for traumatic hemorrhage.

Hemorrhage remains a big threat to trauma patients, especially in combat fields. Therefore, we formulated a biocompatible and biopolymer based chitosan/carrageenan composite dressing. This dressing was fabricated using freeze-drying that will serve as a promising material to promote hemostasis and tissue growth required during hemorrhage. The efficacy of dressing was evaluated for its physiochemical analysis, surface morphology, and biodegradability. Further, human dermal fibroblast cells were seeded on dressing and demonstrated non-toxic effects on the cells by showing enhanced cell attachment and proliferation. In vitro hemostatic properties of the dressing were analyzed by human Thrombin-Antithrombin assay. The dressing formed showed steady blood coagulation implying red blood cells and platelet adhesion that helped in thrombin formation, which is responsible for enhancing wound healing. Thus, it is concluded that the composite dressing can be a potent combination to accelerate hemostatic activity against hemorrhage and promote tissue growth for effective wound healing.

A rare occurrence of accidental exposure to UV radiation among operating theatre personnel.

Ultraviolet (UV) lamps are commonly used in operation theatres for disinfection. Accidental exposure causes damage to superficial tissues especially the skin, the eyes and has the potential to cause various malignancies. Nine previously asymptomatic operation theaters (OT) personnel experienced, foreign body sensation with intense tearing of eyes and erythematous rash on exposed body parts 2 to 4 hours after leaving work. They required symptomatic treatment with oral and topical antihistaminics and lubricant eye drops. Two of the nine required intravenous steroids. UV exposure was diagnosed as diagnosis of exclusion. There is a lack of knowledge regarding presence UV radiation in OT and a lack of safety measures in place to prevent exposure. This case report emphasises the threats poses by UV exposure, the need to bring about awareness about the presence of UV lamps and adopting safety measures to avoid exposure among healthcare providers.

Cadmium versus Lanthanum Effects on Spontaneous Electrical Activity and Expression of Connexin Isoforms Cx26, Cx36, and Cx45 in the Human Fetal Cortex.

Electrical activity is important for brain development. In brain slices, human subplate neurons exhibit spontaneous electrical activity that is highly sensitive to lanthanum. Based on the results of pharmacological experiments in human fetal tissue, we hypothesized that hemichannel-forming connexin (Cx) isoforms 26, 36, and 45 would be expressed on neurons in the subplate (SP) zone. RNA sequencing of dissected human cortical mantles at ages of 17-23 gestational weeks revealed that Cx45 has the highest expression, followed by Cx36 and Cx26. The levels of Cx and pannexin expression between male and female fetal cortices were not significantly different. Immunohistochemical analysis detected Cx45- and Cx26-expressing neurons in the upper segment of the SP zone. Cx45 was present on the cell bodies of human SP neurons, while Cx26 was found on both cell bodies and dendrites. Cx45, Cx36, and Cx26 were strongly expressed in the cortical plate, where newborn migrating neurons line up to form cortical layers. New information about the expression of 3 "neuronal" Cx isoforms in each cortical layer/zone (e.g., SP, cortical plate) and pharmacological data with cadmium and lanthanum may improve our understanding of the cellular mechanisms underlying neuronal development in human fetuses and potential vulnerabilities.

Pneumothorax Following Bougie-guided Intubation in a Difficult Airway: A Report of Two Cases.

Patients coming for atlantoaxial dislocation surgery represent a unique subset of difficult intubation. In addition to having restricted neck movements, excessive movements at the neck joint during intubation must be avoided to avoid further compression. In view of the anticipated difficult intubation, adjuncts or introducers may be required to aid intubation, the most commonly used being bougies. Complications are known to occur with the use of bougies but fortunately the incidences are far and few. The most dreaded of these is pneumothorax, secondary to trauma by the bougie. The use of an adult bougie for pediatric intubations could possibly increase the risk of the same. Here, we report two incidences of pneumothorax after bougie-guided intubation.