The association of histopathologic features after neoadjuvant chemo-immunotherapy with clinical outcome: Sub-analyses from the randomized double-blinded, placebo-controlled, Phase III IMagyn050/GOG3015/ENGOT-ov39 study.

OBJECTIVE: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes. METHODS: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes. RESULTS: The predefined population had 243 evaluable NACT patients, with 48.1% tumors being PD-L1-positive. No statistically significant differences in PFS (16.9 months vs. 19.2 months, p = 0.21) or OS (41.5 months vs. 45.1 months, p = 0.67) between treatment arms were seen. Substantial residual tumor (RT) (3+) was identified in 26% atezolizumab vs. 24% placebo arms (p = 0.94). Most showed no (1+) necrosis (82% vs. 96%, respectively, p = 0.69), moderate (2+) to severe (3+) fibrosis (71% vs. 75%, respectively, p = 0.82), and extensive (2+) inflammation (53% vs. 47% respectively, p = 0.48). No significant histopathologic differences were identified by tissue site or by arm. Multivariate analyses showed increased risk for progression with moderate and substantial RT (13.6 mon vs. 21.1 mon, hazard ratio 2.0, p < 0.01; 13.6 mon vs. 21.1 mon, HR 1.9, p < 0.01, respectively); but decreased risk for death with extensive inflammation (46.9 mon vs. 36.3 mon, HR 0.65, p = 0.02). Inflammation also correlated with greater likelihood of response to NACT/bevacizumab plus immunotherapy (odds ratio 2.9, p < 0.01). Modeling showed inflammation as a consistent but modest predictor for OS. CONCLUSIONS: Detailed histologic assessment of ICS specimens appear to identify characteristics, such as inflammation and residual tumor, that may provide insight to certain clinical outcomes. Future work potentially leveraging emerging tools may provide further insight into outcomes.

Leishmania donovani Infection with Atypical Cutaneous Manifestations, Himachal Pradesh, India, 2014-2018.

We conducted a molecular study of parasite sequences from a cohort of cutaneous leishmaniasis patients in Himachal Pradesh, India. Results revealed atypical cutaneous disease caused by Leishmania donovani parasites. L. donovani variants causing cutaneous manifestations in this region are different from those causing visceral leishmaniasis in northeastern India.

A case report of pulmonary alveolar microlithiasis with pulmonary tuberculosis.

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterised by the deposition of calcium phosphate microliths in the alveoli. PAM has been reported in all continents and there is often a familial history. There is clinical-radiological dissociation as there is often a paucity of symptoms in contrast to the imaging findings. Patients often remain asymptomatic until the third or fourth decade of life, and dyspnea is the most common symptom. PAM is caused by a mutation within the solute carrier family 34 member 2 gene (the SLC34A2 gene) located on chromosome 4p15.2, which encodes a sodium/phosphate co-transporter. The imaging appearance of the disease is quite pathognomic with the high-resolution computed tomography (HRCT) demonstrating a diffuse micronodular appearance. Transbronchial lung biopsy also confirms the diagnosis. There is no effective therapy at present except lung transplantation. We herein, present a case of PAM along with clinical history, imaging study, histopathological study and genetic study of a 43-year-old female adult patient along with genetic analysis.

Complex neurocysticercosis lesions on imaging: Explained through correlative histomorphology.

OBJECTIVES: Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish radio-histo-morphological equivalents of early events in degeneration of the parasite to explain such imaging phenotypes. METHODS: We compared patterns of degeneration in 23 randomly selected complex NCC on MRI with histo-morphology in 30 cysts obtained from an unrelated post mortem brain. RESULTS: The anatomy of the parasite and the degenerative patterns of the scolex (hydropic changes, calcification, evagination, and fragmentation) and the cyst wall (undulation, accessory loculi, and frank disruption) were well demonstrated on both. The intact scolex remarkably resembled head of intestinal Taenia. The complex lesions were conglomeration of multiple communicating cysts with a single parent cyst and multiple daughter cysts. The parent cysts contained a solitary variably degenerated scolex, had thicker walls and associated chronic inflammation. The remaining cysts of the lesion complex contained no scolex, had poorly organized walls, turbid contents, and florid perilesional enhancement with leakage of contrast. Three lesions assumed a multi-cystic pseudo-tumorous pattern, of which two resolved into solitary calcific remnants on follow up. CONCLUSION: Complex lesion in NCC result from degeneration of solitary parasite with perilesional gliosis, surrounded by multiple non-larval daughter cysts inciting acute intra and perilesional inflammation due to enhanced antigenic challenge. Possibly, attempted abortive asexual reproduction by the cellulose cyst as a preterminal event results in a "limited Racemose like transition." Correct interpretation has diagnostic and therapeutic implications as active lesions and their fibrocalcific residue may have greater epileptogenic potential.

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39).

PURPOSE: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). METHODS: This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations. RESULTS: Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). CONCLUSION: Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.

Quality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival.

BACKGROUND: There is a critical need to identify patient characteristics associated with long-term ovarian cancer survival. METHODS: Quality of life (QOL), measured by the Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI), including physical, functional, and ovarian-specific subscales, was compared between long-term survivors (LTS) (8+ years) and short-term survivors (STS) (<5 years) of GOG 218 at baseline; before cycles 4, 7, 13, 21; and 6 months post-treatment using linear and longitudinal mixed models adjusted for covariates. Adverse events (AEs) were compared between survivor groups at each assessment using generalized linear models. All P values are 2-sided. RESULTS: QOL differed statistically significantly between STS (N = 1115) and LTS (N = 260) (P < .001). Baseline FACT-O-TOI and FACT-O-TOI change were independently associated with long-term survival (odds ratio = 1.05, 95% confidence interval = 1.03 to 1.06 and odds ratio = 1.06, 95% confidence interval = 1.05 to 1.07, respectively). A 7-point increase in baseline QOL was associated with a 38.0% increase in probability of LTS, and a 9-point increase in QOL change was associated with a 67.0% increase in odds for LTS. QOL decreased statistically significantly with increasing AE quartiles (cycle 4 quartiles: 0-5 vs 6-8 vs 9-11 vs ≥12 AEs, P = .01; cycle 21 quartiles: 0-2 vs 3 vs 4-5 vs ≥6 AEs, P = .001). Further, LTS reported statistically significantly better QOL compared with STS (P = .03 and P = .01, cycles 4 and 21, respectively), with similar findings across higher AE grades. CONCLUSIONS: Baseline and longitudinal QOL change scores distinguished LTS vs STS and are robust prognosticators for long-term survival. Results have trial design and supportive care implications, providing meaningful prognostic value in this understudied population.

Ziehl-Neelsen sputum smear microscopy image database: a resource to facilitate automated bacilli detection for tuberculosis diagnosis.

Ziehl-Neelsen stained microscopy is a crucial bacteriological test for tuberculosis detection, but its sensitivity is poor. According to the World Health Organization (WHO) recommendation, 300 viewfields should be analyzed to augment sensitivity, but only a few viewfields are examined due to patient load. Therefore, tuberculosis diagnosis through automated capture of the focused image (autofocusing), stitching of viewfields to form mosaics (autostitching), and automatic bacilli segmentation (grading) can significantly improve the sensitivity. However, the lack of unified datasets impedes the development of robust algorithms in these three domains. Therefore, the Ziehl-Neelsen sputum smear microscopy image database (ZNSM iDB) has been developed, and is freely available. This database contains seven categories of diverse datasets acquired from three different bright-field microscopes. Datasets related to autofocusing, autostitching, and manually segmenting bacilli can be used for developing algorithms, whereas the other four datasets are provided to streamline the sensitivity and specificity. All three categories of datasets were validated using different automated algorithms. As images available in this database have distinctive presentations with high noise and artifacts, this referral resource can also be used for the validation of robust detection algorithms. The ZNSM-iDB also assists for the development of methods in automated microscopy.

Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study.

PURPOSE: The primary objective was to establish noninferiority of laparoscopy compared with laparotomy for recurrence after surgical staging of uterine cancer. PATIENTS AND METHODS: Patients with clinical stages I to IIA disease were randomly allocated (two to one) to laparoscopy (n = 1,696) versus laparotomy (n = 920) for hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The primary study end point was noninferiority of recurrence-free interval defined as no more than a 40% increase in the risk of recurrence with laparoscopy compared with laparotomy. RESULTS: With a median follow-up time of 59 months for 2,181 patients still alive, there were 309 recurrences (210 laparoscopy; 99 laparotomy) and 350 deaths (229 laparoscopy; 121 laparotomy). The estimated hazard ratio for laparoscopy relative to laparotomy was 1.14 (90% lower bound, 0.92; 95% upper bound, 1.46), falling short of the protocol-specified definition of noninferiority. However, the actual recurrence rates were substantially lower than anticipated, resulting in an estimated 3-year recurrence rate of 11.4% with laparoscopy and 10.2% with laparotomy, or a difference of 1.14% (90% lower bound, -1.28; 95% upper bound, 4.0). The estimated 5-year overall survival was almost identical in both arms at 89.8%. CONCLUSION: This study previously reported that laparoscopic surgical management of uterine cancer is superior for short-term safety and length-of-stay end points. The potential for increased risk of cancer recurrence with laparoscopy versus laparotomy was quantified and found to be small, providing accurate information for decision making for women with uterine cancer.

Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer: gynecologic oncology group trial 129-P.

PURPOSE A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)-supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. PATIENTS AND METHODS Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m(2) as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). CONCLUSION In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.

Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.

PURPOSE: The objective was to compare laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer. PATIENTS AND METHODS: Patients with clinical stage I to IIA uterine cancer were randomly assigned to laparoscopy (n = 1,696) or open laparotomy (n = 920), including hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The main study end points were 6-week morbidity and mortality, hospital length of stay, conversion from laparoscopy to laparotomy, recurrence-free survival, site of recurrence, and patient-reported quality-of-life outcomes. RESULTS: Laparoscopy was initiated in 1,682 patients and completed without conversion in 1,248 patients (74.2%). Conversion from laparoscopy to laparotomy was secondary to poor visibility in 246 patients (14.6%), metastatic cancer in 69 patients (4.1%), bleeding in 49 patients (2.9%), and other cause in 70 patients (4.2%). Laparoscopy had fewer moderate to severe postoperative adverse events than laparotomy (14% v 21%, respectively; P < .0001) but similar rates of intraoperative complications, despite having a significantly longer operative time (median, 204 v 130 minutes, respectively; P < .001). Hospitalization of more than 2 days was significantly lower in laparoscopy versus laparotomy patients (52% v 94%, respectively; P < .0001). Pelvic and para-aortic nodes were not removed in 8% of laparoscopy patients and 4% of laparotomy patients (P < .0001). No difference in overall detection of advanced stage (stage IIIA, IIIC, or IVB) was seen (17% of laparoscopy patients v 17% of laparotomy patients; P = .841). CONCLUSION: Laparoscopic surgical staging for uterine cancer is feasible and safe in terms of short-term outcomes and results in fewer complications and shorter hospital stay. Follow-up of these patients will determine whether surgical technique impacts pattern of recurrence or disease-free survival.