Mixed Goblet Cell Carcinoid-Adenocarcinoma: A Case Series

INTRODUCTION: Mixed goblet cell carcinoid-adenocarcinoma (GCC) tumors are a group of rare heterogenous neoplasms of the appendix accounting for \u3c 5% of all primary appendiceal tumors. They are characterized as an intermediate between classic carcinoid tumors and appendiceal adenocarcinomas, exhibiting both neuroendocrine and glandular/mucinous morphology that most commonly presents in Caucasian females in the fifth and sixth decades. We present three cases of mixed GCC presenting as acute appendicitis. CASE PRESENTATION: Case #1 A 65-year-old male presented with RLQ pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed perforated appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid, signet ring type extending through the muscularis propria into the mesoappendix measuring \u3e3cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a right hemicolectomy and partial omentectomy. Pathology revealed normal ileal, omental, and colonic tissue without evidence of carcinoma. 0/12 nodes were positive. Case #2 A 49-year-old male presented with periumbilical pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade, poorly differentiated, adenocarcinoma ex goblet cell carcinoid invading through the muscularis propria into the periappendiceal soft tissue measuring 1.5cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a laparoscopic right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/14 nodes were positive. Case #3 A 70-year-old female presented with periumbilical pain. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid extending through the muscularis propria into the mesoappendix measuring 4cm. Patient then underwent an exploratory laparotomy with a right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/21 nodes were positive. CONCLUSION: Mixed GCC tumors are rare tumors that tend to present at an advanced stage and most commonly spread via direct extension. Surgical resection with a right hemi-colectomy after an appendectomy has been shown to improve the prognosis. HIPEC and adjuvant chemotherapy are other therapeutic options, but have not been shown to improve survival. In the current age of increasing rates of managing acute appendicitis non-operatively we strongly encourage surgical appendectomy in patients older than 45 years of age to avoid missing this important diagnosis and the opportunity to treat it in a timely manner

Endometrial Thinning after Ovarian Stimulation using Letrozole or Clomiphene Citrate: A Randomized Trial

Objective: To compare endometrial thickness after three consecutive cycles of ovulation induction with clomiphene citrate versus letrozole. Methods: Eighty-four women with normal menstrual interval who attended the university infertility clinic from June 2016 to March 2017 were eligible for the study. After the endometrial thickness of baseline cycle was recorded, all participants were randomized into two groups of clomiphene citrate or letrozole treatment for three consecutive cycles. Endometrial thickness and estradiol level were measured when at least one follicle reached 17 mm in diameter. The differences in endometrial thickness relative to baseline of the two groups were compared. Results: A total of 62 patients completed three cycles of ovarian stimulation. Both drugs resulted in significantly thinner endometrium compared with the baseline cycle thickness. The mean endometrial thickness was significantly decreased in the clomiphene citrate group compared with letrozole group (7.46 ± 1.71 vs 8.88 ± 2.34 mm, p = 0.029). Estradiol level on the day of induced ovulation was significantly higher in the clomiphene citrate group than in the letrozole group (706.0 (207.9, 2209.0) vs 168.7 (30.0, 401.8), p < 0.001). The number of the follicles reaching 17 mm on the day of induced ovulation was higher in the clomiphene citrate group (1.9 ± 0.8 vs 1.4 ± 0.5, p = 0.002). Conclusion: Letrozole had less effect on endometrium thinning after three consecutive cycles of induced ovulation compared with clomiphene citrate

Obstetric and Perinatal Outcomes of Singleton Pregnancies After in-vitro Fertilization in Siriraj Hospital, A Matched Case-Control Study

Objective: To compare obstetric and perinatal outcomes between singletons born after IVF and natural conception. Methods: A total of 141 singleton pregnancies conceived by IVF were included. Another 141 singleton pregnancies conceived naturally were randomly selected as comparison group, matched by age. Data were retrospectively extracted from medical records, including baseline characteristics and delivery data. Various characteristics, including pregnancy and neonatal outcomes were compared between groups. Results: Women in IVF group were more likely to be nulliparous and had previous miscarriage (88.7% vs. 76.6%, 0=0.003; and 26.2% vs. 14.8%, p=0.018, respectively). Underlying diseases and complications during pregnancy were comparable between the 2 groups. Mean gestational age was lower in IVF group (37.9 ± 2.0 vs. 38.4 ± 1.6, p=0.008), but without clinical significance. Primary cesarean section was significantly more common among women in IVF group (74.4% vs. 54.6%, p<0.001) and the majority were elective cases (61.9% vs. 23.4%, p<0.001). There were no significant differences in terms of rates of preterm labor, birth weight, low birth weight, small for gestational age, neonatal intensive care unit admissions, and perinatal mortality. Conclusion: Singleton pregnancies after IVF were not associated with higher risks of adverse obstetric and perinatal outcomes, compared with naturally conceived group, but IVF pregnancies are associated with a high rate of cesarean sections

Non-invasive real-time imaging of reactive oxygen species (ROS) using auto-fluorescence multispectral imaging technique: a novel tool for redox biology

Detecting reactive oxygen species (ROS) that play a critical role as redox modulators and signalling molecules in biological systems currently requires invasive methods such as ROS -specific indicators for imaging and quantification. We developed a non-invasive, real-time, label-free imaging technique for assessing the level of ROS in live cells and thawed cryopreserved tissues that is compatible with in-vivo imaging. The technique is based on autofluorescence multispectral imaging (AFMI) carried out in an adapted fluorescence microscope with an expanded number of spectral channels spanning specific excitation (365 nm-495 nm) and emission (420 nm-700 nm) wavelength ranges. We established a strong quantitative correlation between the spectral information obtained from AFMI and the level of ROS obtained from CellROX staining. The results were obtained in several cell types (HeLa, PANC1 and mesenchymal stem cells) and in live kidney tissue. Additioanly,two spectral regimes were considered: with and without UV excitation (wavelengths > 400 nm); the latter being suitable for UV-sensitive systems such as the eye. Data were analyzed by linear regression combined with an optimization method of swarm intelligence. This allowed the calibration of AFMI signals to the level of ROS with excellent correlation (R = 0.84, p = 0.00) in the entire spectral range and very good correlation (R = 0.78, p = 0.00) in the limited, UV-free spectral range. We also developed a strong classifier which allowed us to distinguish moderate and high levels of ROS in these two regimes (AUC = 0.91 in the entire spectral range and AUC = 0.78 for UV-free imaging). These results indicate that ROS in cells and tissues can be imaged non-invasively, which opens the way to future clinical applications in conditions where reactive oxygen species are known to contribute to progressive disease such as in ophthalmology, diabetes, kidney disease, cancer and neurodegenerative diseases.Abbas Habibalahi, Mahdieh Dashtbani Moghari, Jared M. Campbell, Ayad G. Anwer, Saabah B. Mahbub, Martin Gosnell, Sonia Saad, Carol Pollock, Ewa M. Goldy

Pandemic potential of highly pathogenic avian influenza clade 2.3.4.4 A(H5) viruses

The panzootic caused by A/goose/Guangdong/1/96-lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human-to-human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human-to-human transmissibility and impact on human health should such human-to-human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts

Eureka and beyond: mining's impact on African urbanisation

This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

Defining remission in childhood-onset lupus:PReS-endorsed consensus definitions by an international task force

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score &lt; 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P <.001) and grade III to IV acute GVHD (RR, 1.93; P =.006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P =.008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit