Search results for: nasopharynx lymphomas

Authors: Jiajia Peng, Jianqing Qiu, Jianjun Ren, Yu Zhao

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Background: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity, nasopharynx and paranasal sinuses, which are always categorized as one sinonasal type. Methods: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from the SEER database were included. We identified these patients based on histological types and anatomical sites and subsequently conducted univariate and multivariate Cox regression and Kaplan–Meier analyses to examine cancer-special survival (CSS) outcomes. Results: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the CSS outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (HR:3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of the higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in those with NKT-NHL in the nasopharynx site. However, chemotherapy has only been beneficial for CSS in patients with B-NHL in paranasal sinuses (HR: 0.42) since 2010, rather than in other types of B-NHL or NKT-NHL. Conclusions: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinic demographics and prognoses are largely different and should be treated and studied as distinct diseases.

Keywords: B-cell non-Hodgkin lymphomas, NKT-cell non-Hodgkin lymphomas, nasal cavity lymphomas, nasal sinuses lymphomas, nasopharynx lymphomas

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Authors: Jiajia Peng, Danni Cheng, Jianqing Qiu, Yufang Rao, Minzi Mao, Ke Qiu, Junhong Li, Fei Chen, Feng Liu, Jun Liu, Xiaosong Mu, Wenxin Yu, Wei Zhang, Wei Xu, Yu Zhao, Jianjun Ren

Abstract:

Background: Currently, primary B-cell non-Hodgkin lymphoma (B-NHL) and T/NK-cell non-Hodgkin lymphoma (NKT-NHL) originated from the nasal cavity (NC), nasopharynx (NP) and nasal sinus (NS) distinguished unclearly in the clinic. Objective: We sought to compare the clinical and survival differences of B-NHL and NKT-NHL that occurred in NC, NP, and NS, respectively. Methods: Retrospective data of patients diagnosed with nasal cavity lymphoma (NCL), nasopharyngeal lymphoma (NPL), and nasal sinus lymphoma (NSL) between 1975 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were collected. We identified the B/NKT-NHL patients based on the histological type and performed univariate, multivariate, and Kaplan-Meier analyses to investigate the survival rates. Results: Of the identified 3,101 B-NHL and 738 NKT-NHL patients, those with B-NHL in NP were the majority (43%) and had better cancer-specific survival than those in NC and NS from 2010 to 2017 (5-year-CSS, NC vs. NP vs. NS: 81% vs. 83% vs. 82%). In contrast, most of the NKT-NHL originated from NC (68%) and had the highest CSS rate in the recent seven years (2010-2017, 5-year-CSS: 63%). Additionally, the survival outcomes of patients with NKT-NHL-NP (HR: 1.34, 95% CI: 0.62-2.89, P=0.460) who had received surgery were much worse than those of patients with NKT-NHL-NC (HR: 1.07, 95% CI: 0.75-1.52, P=0.710) and NKT-NHL-NS (HR: 1.11, 95% CI: 0.59-2.07, P=0.740). NKT-NHL-NS patients who had radiation performed (HR: 0.38, 95% CI: 0.19-0.73, P=0.004) showed the highest survival rates, while chemotherapy performed (HR: 1.01, 95% CI: 0.43-2.37, P=0.980) presented opposite results. Conclusions: Although B-NHL and NKT-NHL originating from NC, NP and NS had similar anatomical locations, their clinical characteristics, treatment therapies, and prognoses were different in this study. Our findings may suggest that B-NHL and NKT-NHL in NC, NP, and NS should be treated as different diseases in the clinic.

Keywords: nasopharyngeal lymphoma, nasal cavity lymphoma, nasal sinus lymphoma, B-cell non-Hodgkin lymphoma, T/NK-cell non-Hodgkin lymphoma

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Authors: A. S. El Naas, K. S. Ganghish, A. O. Booker, O. Elwaer

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10 out of 40 camels examined at Tripoli slaughter places were infected with the camel nasal bot fly Cephalopenia titillator. The larvae occurred mainly in the nasopharynx and occasionally the larvae were found embedded between turbinated bones. The nasal cavity was congested and filled with mucus in which some larvae were entangled. This work is undertaken to determine the Prevalence of Cephalopenia titillator of camel slaughtered in Tripoli-Libya.

Keywords: Cephalopenia titillator, camels, Libya, larvae, nasopharynx

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Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

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Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: Laila Seada, Nouf Al Gharbi, Shaimaa Dawa

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Although skin cancers are prevalent worldwide, it is uncommon in Ha’il region in the Kingdom of Saudi Arabia, mostly non-melanoma sub-type. During a 4-year period from 2014 to 2017, out of a total of 120 cases of skin lesions, 29 non-melanoma cancers were retrieved from histopathology files obtained from King Khalid Hospital. As part of the study, all cases of skin cancer diagnosed during 2014 -2017 have been revised and the clinicopathological data recorded. The results show that Basal cell carcinoma (BCC) was the most common neoplasm (36%), followed by cutaneous lymphomas (mostly mycosis fungoides 25%), squamous cell carcinoma (SCC) (21%) and dermatofibrosarcoma protuberans (DFSP) (11%). Only one case of metastatic carcinoma was recorded. BCC nodular type was the most prevalent, with a mean age 57.6 years and mean size 2.73 cm. SCC was mostly grade 2, with mean size 1.9 cm and an older mean age of 72.3 cm. Increased size of lesion positively correlated with older age (p = 0.001). Non-melanoma skin cancer in Ha’il region is not frequently encountered. BCC is the most frequent followed by cutaneous T-cell lymphomas and SCC. The findings in this study were in accordance with other parts of, but much lower than other parts of the world.

Keywords: non melanoma skin cancer, Hail Region, histopathology, BCC

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: Laila Seada, Hanan Oreiby, Fawaz Al Rashid, Ashraf Negm

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Background and Objective: In most areas of the world, the incidence of thyroid cancer has been increasing over the last decade, mostly due to a combination of early detection of the neoplasm resulting from sensitive procedures and increased population exposure to radiation and unrecognized carcinogens. Methods: Cases of thyroid cancer have been retrieved from the cancer registry at King Khalid Hospital during the period from August 2012 to April 2016. Age, gender and histopathologic types have been recorded. Results: Thyroid carcinoma ranked as the second most common malignancy in females (25%) after breast cancer (31%). It constituted 20.8% of all newly diagnosed cancer cases. As for males, it ranked the 4^th type of malignancy after gastrointestinal cancer, lymphomas and soft tissue sarcomas. Mean age for females and males was 38.7 +/- 13.2 and 60.25 +/- 11.5 years, respectively, and the difference between the two groups was statistically significant (p value = 0.0001). Fifty-five (82%) were papillary carcinomas including 10 follicular variant of papillary (FVPC), and eight papillary micro carcinomas (PMC) and two tall cell/oncocytic variants. Follicular carcinomas constituted two (3.1%), while two (3.1%) were anaplastic, and two (3.1%) were medullary. Conclusion: Thyroid cancer incidence in Hail is ranking as the 2^nd most common female malignancy similar to other regions in the Kingdom. However, this high incidence contrasts with much lower rates worldwide.

Keywords: thyroid, hail, papillary, microcarcinoma

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Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez

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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.

Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis

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Authors: Adam M. Pitz, Gillian L. Phillipson, Jayant E. Khanolkar, Andrew M. Middleton

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New emerging evidence suggests that the nose is the predominant route for entry of the SARS-CoV-2 virus into the host. A virucidal suspension test (conforming in principle to the European Standard EN14476) was conducted to determine whether a commercial liquid gel intranasal spray containing 1% of the mucoadhesive hydroxypropyl methylcellulose (HPMC) could inhibit the cellular infectivity of the SARS-CoV-2 coronavirus. Virus was added to the test product samples and to controls in a 1:8 ratio and mixed with one part bovine serum albumin as an interfering substance. The test samples were pre-equilibrated to 34 ± 2°C (representing the temperature of the nasopharynx) with the temperature maintained at 34 ± 2°C for virus contact times of 1, 5 and 10 minutes. Neutralized aliquots were inoculated onto host cells (Vero E6 cells, ATCC CRL-1586). The host cells were then incubated at 36 ± 2°C for a period of 7 days. The residual infectious virus in both test and controls was detected by viral-induced cytopathic effect. The 50% tissue culture infective dose per mL (TCID50/mL) was determined using the Spearman-Karber method with results reported as the reduction of the virus titer due to treatment with test product, expressed as log10. The controls confirmed the validity of the results with no cytotoxicity or viral interference observed in the neutralized test product samples. The HPMC formulation reduced SARS-CoV-2 titer, expressed as log10TCID50, by 2.30 ( ± 0.17), 2.60 ( ± 0.19), and 3.88 ( ± 0.19) with the respective contact times of 1, 5 and 10 minutes. The results demonstrate that this 1% HPMC gel formulation can reduce the cellular infectivity of the SARS-CoV-2 virus with an increasing viral inhibition observed with increasing exposure time. This 1% HMPC gel is well tolerated and can reside, when delivered via nasal spray, for up to one hour in the nasal cavity. We conclude that this intranasal gel spray with 1% HPMC repeat-dosed every few hours may offer an effective preventive or early intervention solution to limit the transmission and impact of the SARS-CoV-2 coronavirus.

Keywords: hydroxypropyl methylcellulose, mucoadhesive nasal spray, respiratory viruses, SARS-CoV-2

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Authors: Saba Amreen Syeda, Summaiah Asim, Syeda, Hafsa, Essam Quraishi

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Mantle Cell Lymphoma (MCL) is a relatively uncommon type of lymphoma that comprises approximately 7 percent of non hodgkin's lymphomas (NHL), Classic MCL presents mostly in lymph nodes and occasionally in extranodal sites. About 26 % of MCL is present primarily in the Gastrointestinal tract. While both the upper GI tract and the lower GI tract could be involved, it is rare to present with concurrent upper and lower GI involvement with MCL. We present the case of a 51-year-old Asian Indian male that presented to our clinic with complaints of chronic diarrhea for the last one year, progressively worsening over the past three months. The Patient also reported black stool as well as bright red blood per rectum. Patient reported severe fatigue on minimal exertion. On a physical exam, the patient was noted to have matted lymphadenopathy in the neck. Patient was noted to be anemic with a hemoglobin to be 8 g/dl. Esophagogastroduodenoscopy and colonoscopy was performed. EGD showed a large 4 cm ulcer in the gastric antrum with thick heaped up edges. There was bleeding on contact. Colonoscopy showed a large 35 mm multilobulated polyp in the ascending colon, which was biopsied. The patient was also noted to have nodular proctitis in the mid rectum. This was localized and extended to about 5 cm. This area was biopsied as well. Biopsies from the stomach, colon, as well as the rectum, returned with findings of mantle cell lymphoma on pathology. Lymphoid cells in the biopsy were stained strongly positive for CD 20, cyclin D1, and CD 5. There was the absence of stain for CD 3 and CD 10. The IHC stain for CD 23 was negative. Biopsies from neck LAD were obtained and were also positive for MCL. The patient was referred to oncology for staging and treatment.

Keywords: mantle cell lymphoma, GI bleed, diarrhea, gastric ulcer, colon polyp

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Maximiliano Guerra, Lexi Frankel, Amalia D. Ardeljan, Sarah Ghali, Diya Kohli, Omar M. Rashid.

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Introduction/Background: Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of these bacteria throughout the body. This can result in a proinflammatory state and colonization particularly in the lungs. Recent studies have failed to determine a link between H. Influenzae colonization and prostate cancer, despite previous research demonstrating the presence of proinflammatory states in preneoplastic and neoplastic prostate lesions. Given these contradictory findings, the primary goal of this study was to evaluate the correlation between H. Influenzae infection and the incidence of prostate cancer. Methods: To evaluate the incidence of Haemophilus influenzae infection and the development of prostate cancer in the future we used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. We were afforded access to this database by Holy Cross Health, Fort Lauderdale for the express purpose of academic research. Standard statistical methods were employed in this study including Pearson’s chi-square tests. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 13, 691 patients in both the control and C. difficile infected groups, respectively. The two groups were matched by age range and CCI score. In the Haemophilus influenzae infected group, the incidence of prostate cancer was 1.46%, while the incidence of the prostate cancer control group was 4.56%. The observed difference in cancer incidence was determined to be a statistically significant p-value (< 2.2x10^-16). This suggests that patients with a history of C. difficile have less risk of developing prostate cancer (OR 0.425, 95% CI: 0.382 - 0.472). Treatment bias was considered, the data was analyzed and resulted in two groups matched groups of 3,208 patients in both the infected with H. Influenzae treated group and the control who used the same medications for a different cause. Patients infected with H. Influenzae and treated had an incidence of prostate cancer of 2.49% whereas the control group incidence of prostate cancer was 4.92% with a p-value (< 2.2x10^-16) OR 0.455 CI 95% (0.526 -0.754), proving that the initial results were not due to the use of medications. Conclusion: The findings of our study reveal a statistically significant correlation between H. Influenzae infection and a decreased incidence of prostate cancer. Our findings suggest that prior infection with H. Influenzae may confer some degree of protection to patients and reduce their risk for developing prostate cancer. Future research is recommended to further characterize the potential role of Haemophilus influenzae in the pathogenesis of prostate cancer.

Keywords: Haemophilus Influenzae, incidence, prostate cancer, risk.

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Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang

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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.

Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree

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Authors: Karthik Chamari, Vasudha Rudraraju, Gaurav Chaudhari

Abstract:

Background: Mantle cell lymphoma (MCL) is one of the mature B cell non-Hodgkin lymphomas (NHL). The course of MCL is moderately aggressive and variable, and it has median overall survival of 8 to 10 years. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, was approved by the United States (US) Food and Drug Administration in November of 2013 for the treatment of MCL patients who have received at least one prior therapy. In this study, we aimed to evaluate whether there has been a change in survival and patterns of second primary malignancies (SPMs) among the MCL population in the US after ibrutinib approval. Methods: Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-18, we conducted a retrospective study with patients diagnosed with MCL (ICD-0-3 code 9673/3) between 2007 and 2018. We divided patients into two six-year cohorts, pre-ibrutinib approval (2007-2012) and post-ibrutinib approval (2013-2018), and compared relative survival rates (RSRs) and standardized incidence ratios (SIRs) of SPMs between cohorts. Results: We included 9,257 patients diagnosed with MCL between 2007 and 2018 in the SEER-18 survival and SIR registries. Of these, 4,205 (45%) patients were included in the pre-ibrutinib cohort, and 5052 (55%) patients were included in the post-ibrutinib cohort. The median follow-up duration for the pre-ibrutinib cohort was 54 months (range 0 to 143 months), and the post-ibrutinib cohort was 20 months (range 0 to 71 months). There was a significant difference in the five-year RSRs between pre-ibrutinib and post-ibrutinib cohorts (57.5% vs. 62.6%, p < 0.005). Out of the 9,257 patients diagnosed with MCL, 920 developed SPMs. A higher proportion of SPMs occurred in the post-ibrutinib cohort (63%) when compared with the pre-ibrutinib cohort (37%). Non-hematological malignancies comprised most of all SPMs. A higher incidence of non-hematological malignancies occurred in the post-ibrutinib cohort (SIR 1.42, 95% CI 1.29 to 1.56) when compared with the pre-ibrutinib cohort (SIR 1.14, 95% CI 1 to 1.3). There was a statistically significant increase in the incidence of cancers of the respiratory tract (SIR 1.77, 95% CI 1.43 to 2.18), urinary tract (SIR 1.61, 95% CI 1.23 to 2.06) when compared with other non-hematological malignancies in post-ibrutinib cohort. Conclusions: Our study results suggest the relative survival rates have increased since the approval of ibrutinib for mantle cell lymphoma patients. Additionally, for some unclear reasons, the incidence of SPM’s (non-hematological malignancies), mainly cancers of the respiratory tract, urinary tract, have increased in the six years following the approval of ibrutinib. Further studies should be conducted to determine the cause of these findings.

Keywords: mantle cell lymphoma, Ibrutinib, relative survival analysis, secondary primary cancers

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Authors: J. Manuel Bello-López, Julieta Rojo-Medina

Abstract:

Introduction: The transplant of Umbilical Cord Blood Units (UCBU) are a therapeutic possibility for patients with oncohaematological disorders, especially in children. In Mexico, 48.5% of oncological diseases in children 1-4 years old are leukemias; whereas in patients 5-14 and 15-24 years old, lymphomas and leukemias represent the second and third cause of death in these groups respectively. Therefore it is necessary to have more registries of UCBU in order to ensure genetic diversity in the country; the above because the search for appropriate a UCBU is increasingly difficult for patients of mixed ethnicity. Objective: To estimate the genetic diversity (polymorphisms) of Human Leucocyte Antigen (HLA) Class I (A, B) and Class II (DRB1) in UCBU cryopreserved for transplant at Cord Blood Bank of the NCBT. Material and Methods: HLA typing of 533 UCBU for transplant was performed from 2003-2012 at the Histocompatibility Laboratory from the Research Department (evaluated by Los Angeles Ca. Immunogenetics Center) of the NCBT. Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity detected by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. A strict analysis of populations genetic parameters were done in 5 representative UCBU populations. Results: 46.5% of UCBU were collected from Mexico City, State of Mexico (30.95%), Puebla (8.06%), Morelos (6.37%) and Veracruz (3.37%). The remaining UCBU (4.75%) are represented by other states. The identified genotypes correspond to Amerindian origins (HLA-A*02, 31; HLA-B*39, 15, 48), Caucasian (HLA-A*02, 68, 01, 30, 31; HLA-B*35, 15, 40, 44, 07 y HLA-DRB1*04, 08, 07, 15, 03, 14), Oriental (HLA-A*02, 30, 01, 31; HLA-B* 35, 39, 15, 40, 44, 07,48 y HLA-DRB1*04, 07,15, 03) and African (HLA-A*30 y HLA-DRB1*03). The genetic distances obtained by Cavalli-Sforza analysis of the five states showed significant genetic differences by comparing genetic frequencies. The shortest genetic distance exists between Mexico City and the state of Puebla (0.0039) and the largest between Veracruz and Morelos (0.0084). In order to identify significant differences between this states, the ANOVA test was performed. This demonstrates that UCBU is significantly different according to their origin (P <0.05). This is shown by the divergence between arms at the Dendogram of Neighbor-Joining. Conclusions: The NCBT provides UCBU in patients with oncohaematological disorders in all the country. There is a group of patients for which not compatible UCBU can be find due to the mixed ethnic origin. For example, the population of northern Mexico is mostly Caucasian. Most of the NCBT donors are of various ethnic origins, predominantly Amerindians and Caucasians; although some ethnic minorities like Oriental, African and pure Indian ethnics are not represented. The NCBT is, therefore, establishing agreements with different states of Mexico to promote the altruistic donation of Umbilical Cord Blood in order to enrich the genetic diversity in its files.

Keywords: cord blood, genetic diversity, human leucocyte antigen, transplant

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

Abstract:

Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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