Nasal Type Research Articles

Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?

Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive malignancy with significant racial and geographic variations worldwide. In addition to the formerly "nasal-type" initial description, these lymphomas are predominantly extranodal in origin and typically cause vascular damage and tissue destruction, and although not fully understood, Epstein-Barr virus (EBV) has an important role in its pathogenesis. Initial assessment must include a hematopathology review of representative and viable tumor areas without necrosis for adequate immunohistochemistry studies, including EBV-encoded small RNA (EBER) in situ hybridization (ISH). Positron emission tomography with 18-fluorodeoxyglucose (18F-FDG-PET/CT) for accurate staging is essential, and most patients will have localized disease (IE/IIE) at diagnosis. Apart from other T-cell malignancies, the best treatment even for localized cases is combined modality therapy (chemotherapy plus radiotherapy) with non-anthracycline-based regimens. For advanced-stage disease, l-asparaginase-containing regimens have shown improved survival, but relapsed and refractory cases have very poor outcomes. Nowadays, even with a better understanding of pathogenic pathways, up-front therapy is completely based on chemotherapy and radiotherapy, and treatment-related mortality is not low. Future strategies targeting signaling pathways and immunotherapy are evolving, but we need to better identify those patients with dismal outcomes in a pre-emptive way. Given the rarity of the disease, international collaborations are urgently needed, and clinical trials are the way to change the future.

Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive lymphoid malignancy with a poor prognosis and lacks standard treatment. Targeted therapies are urgently needed. Here we systematically investigated the druggable mechanisms through chemogenomic screening and identified that Bcl-xL-specific BH3 mimetics effectively induced ENKTL cell apoptosis. Notably, the specific accumulation of Bcl-xL, but not other Bcl-2 family members, was verified in ENKTL cell lines and patient tissues. Furthermore, Bcl-xL high expression was shown to be closely associated with worse patient survival. The critical role of Bcl-xL in ENKTL cell survival was demonstrated utilizing selective inhibitors, genetic silencing, and a specific degrader. Additionally, the IL2-JAK1/3-STAT5 signaling was implicated in Bcl-xL dysregulation. Invivo, Bcl-xL inhibition reduced tumor burden, increased apoptosis, and prolonged survival in ENKTL cell line xenograft and patient-derived xenograft models. Our study indicates Bcl-xL as a promising therapeutic target for ENKTL, warranting monitoring in ongoing clinical trials by targeting Bcl-xL.

Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma Recurrence at Penile Glans Masquerading Urinary Contamination on 18F-FDG PET/CT.

A 69-year-old man with a history of extranodal NK/T-Cell lymphoma, nasal type (ENKTL-NT) performed an interim 18F-FDG PET/CT for response evaluation. It showed an intense focal uptake at his penile glans, which was suspected as urinary contamination initially. However, he complained with redness and swelling of his penis during further history inquiry. After careful observation, the diagnosis of ENKTL-NT recurrence at penile glans was highly suspected. It was confirmed by percutaneous biopsy of the penile glans finally.

Extranodal Natural Killer/T-cell Lymphoma, Nasal Type, Misdiagnosed as Fungal Sinusitis.

Extranodal Natural Killer/T-cell Lymphoma, Nasal Type, Misdiagnosed as Fungal Sinusitis.

Disseminated Extranodal NK/T-Cell lymphoma, Presenting as an Orbital Mass.

An 84-year-old male patient presented with decreased vision of 20/300 in the right eye, with additional painless upper eyelid fullness, hypoglobus, severe limitation of ocular motility, and conjunctival chemosis of the right eye for several months duration (panel A). He was referred after failing to respond to a trial of oral corticosteroids for presumed orbital myositis. MRI revealed an enlarged enhancing lacrimal gland (arrow), extraocular muscles, and mucosal thickening of the ethmoid sinus (arrowhead) on the right side (panel B). Lacrimal gland biopsy demonstrated medium-sized atypical lymphocytes with irregular nuclear contours, scant-to-moderate amounts of cytoplasm, and brisk mitotic figures (arrow) (panel C, hematoxylin-eosin, ×630), which expressed cytotoxic and natural killer-cell markers CD56 (panel D, ×400), perforin, and T-cell intracellular antigen 1, and were CD4-positive and CD8-negative. Neoplastic cells were positive for Epstein–Barr virus-encoded RNA by in situ hybridization (panel E, ×400). Clinical, morphologic, and immunophenotypic findings were compatible with extranodal natural killer/T-cell lymphoma (natural killer/T-cell lymphoma, nasal type). Optical coherence tomography revealed diffuse choroidal thickening with an undulating anterior border (sea-sick choroid) (arrow), compatible with choroidal involvement by lymphoma (panel F). Positron emission tomography scan showed significantly increased activity in the regional and distal lymph nodes and in multiple bones, compatible with disseminated disease. The patient succumbed to disease shortly after diagnosis. This case highlights the importance of prompt and accurate diagnosis of natural killer/T-cell lymphoma, nasal type, which can present with orbital and ocular involvement simulating an inflammatory process.FIG

Preparation, structure characterization, and stability analysis of peptide-calcium complex derived from porcine nasal cartilage type II collagen.

Porcine nasal cartilage type II collagen-derived peptides (PNCPs) may be complexed with calcium to provide a highly bioavailable, low-cost, and effective calcium food supplement. However, the calcium-binding characteristics of PNCPs have not yet been investigated. In the present study, calcium-binding peptides were derived from porcine nasal cartilage type II collagen and the resulting PNCPs-Ca complex was characterized. The study reveals that the calcium-binding capacity of PNCPs is closely related to enzymatic hydrolysis conditions. The highest calcium-binding capacity of PNCPs was observed at a hydrolysis time of 4 h, temperature of 40 °C, enzyme dosage of 1%, and solid-to-liquid ratio of 1:10. Scanning electron microscopy and energy dispersive X-ray spectroscopy revealed that the PNCPs had a pronounced capacity for calcium binding, with the PNCPs-Ca complex exhibiting a clustered structure consisting of aggregated spherical particles. Fourier-transform infrared spectroscopy, fluorescence spectroscopy, X-ray diffraction, dynamic light scattering, amino acid composition, and molecular weight distribution analyses all indicated that the PNCPs and calcium complexed via the carboxyl oxygen and amino nitrogen atoms, leading to the formation of a β-sheet structure during the chelation process. In addition, the stability of the PNCPs-Ca complex was maintained over a range of pH values consistent with those found in the human gastrointestinal tract, facilitating calcium absorption. These research findings suggest the feasibility of converting by-products from livestock processing into calcium-binding peptides, providing a scientific basis for the development of novel calcium supplements and the potential reduction of resource waste. © 2023 Society of Chemical Industry.

EXTRANODAL NASAL TYPE T/NK CELL LYMPHOMA: CASE REPORT

Female patient, 33 years old, presenting asymptomatic swelling in the right maxilla with elevation of the nose wing, evolving from 30 days, without lymph node enlargement. Computed tomography showed an area of thickening and densification of the skin and subcutaneous tissue at the right nasolabial fold, with contrast enhancement, without a liquefied image and with poorly defined contours with approximately 3.3 cm. A histopathological examination showed fibroconnective tissue with a dense lymphomononuclear inflammatory infiltrate, which was inconclusive. A immunohistochemical study showed presence of lymphocytic infiltrate of small to medium cells with slightly irregular nuclei, with positivity for CD2, CD56, GATA-3, TIA-1 and CD3, and negativity for CD5 and CD7, and a high proliferative index for Ki67 (70-80%). Research for the Epstein-Barr virus revealed diffuse positivity in the tumor cells. The set of findings was suggestive of extranodal T/NK cell lymphoma, nasal type. The patient was referred to hematooncology team. Female patient, 33 years old, presenting asymptomatic swelling in the right maxilla with elevation of the nose wing, evolving from 30 days, without lymph node enlargement. Computed tomography showed an area of thickening and densification of the skin and subcutaneous tissue at the right nasolabial fold, with contrast enhancement, without a liquefied image and with poorly defined contours with approximately 3.3 cm. A histopathological examination showed fibroconnective tissue with a dense lymphomononuclear inflammatory infiltrate, which was inconclusive. A immunohistochemical study showed presence of lymphocytic infiltrate of small to medium cells with slightly irregular nuclei, with positivity for CD2, CD56, GATA-3, TIA-1 and CD3, and negativity for CD5 and CD7, and a high proliferative index for Ki67 (70-80%). Research for the Epstein-Barr virus revealed diffuse positivity in the tumor cells. The set of findings was suggestive of extranodal T/NK cell lymphoma, nasal type. The patient was referred to hematooncology team.

Long-term survival by surgery and adjuvant chemotherapy in a patient with perforated extranodal NK/T-cell lymphoma of the small intestine: a retrospective case study

BackgroundExtranodal natural killer/T-cell lymphoma, nasal type (ENKL) of the small intestine, is a disease with extremely poor prognosis. We describe treatment in a case which is novel in that it demonstrated long-term survival.Case presentationA 68-year-old man was admitted to the emergency department of our hospital with the complaint of severe umbilical pain with tenderness and muscular defense. An abdominal computed tomography scan revealed a thick-wall mass on the small intestine and intra-abdominal free air. He was suspected of perforation of a small intestinal tumor and underwent emergency surgery. The surgery revealed a perforated tumor ulcer, and ENKL was diagnosed from the postoperative pathological findings. The patient’s postoperative course was uneventful. He was further treated with adjuvant chemotherapy by hematologist comprising six courses of dexamethasone, etoposide, ifosfamide, and carboplatin. The patient demonstrated long-term survival and was in remission at the time of writing, four years and five months after surgery.ConclusionsWe report a rare case of long-term survival of perforated ENKL of the small intestine achieved by surgery and adjuvant chemotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin. It is essential to consult with a hematologist to determine the most appropriate chemotherapy such as DeVIC if one encounters rare postoperative pathological findings of ENKL. To elucidate the pathophysiology of this disease and to prolong survival of affected patients, accumulation of cases of long-term survival and examination of associated characteristics is necessary.

Laryngeal NK/T Cell Lymphoma, Nasal Type: Case Report and Literature Review

Extranodal Natural Killer T-cell lymphoma, nasal type represent a rare and aggressive entity of the non-Hodgkin's lymphomas. Laryngeal localization is rare and has a poor prognosis. We report the case of a 66-year-old patient who consulted for dyspnea, dysphonia and dysphagia. Endoscopic examination revealed an endo-laryngeal lesion. Anatomopathological study with immunohistochemistry concluded to a peripheral T NK/T-cell lymphoma nasal type. The extension workup was without abnormalities. Induction chemotherapy without anthracyclines was administered followed by conformal radiotherapy with intensity modulation in arctotherapy. Significant advances have been made over the past decade including better clarification of clinical heterogeneity, more accurate classification using imaging modalities, establishment of new prognostic models, and sequential use of anthracycline-free radiotherapy and chemotherapy in early stages and risk-adapted first-line treatment strategies in advanced stages.

Clinical characteristics, survival outcomes, and prognostic factors in extranodal natural killer/T-cell lymphoma, nasal type: The National Cancer Database study (2004-2019).

7575 Background: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare and aggressive Epstein-Barr virus driven lymphoma, which is most prevalent in East Asia and Latin America. There have been very few large studies outside of Asia. Therapeutic and survival outcomes have not been well characterized in the US. Methods: The National Cancer Database was queried for patients who were diagnosed at aged ≥18 years between 2004 and 2019. Patients who were lost to follow-up were excluded. Kaplan-Meier and multivariate Cox regression analyses were performed. Results: The cohort consists of 2,036 evaluable patients with 68% males, 74% Caucasian, 22% Hispanic Caucasian and 9% African American. The median age at diagnosis was 54 (18-90) years. The median follow up was 71 months (95% CI 66.8-75.7). Early-stage disease (I and II) was reported in 64% while advanced stage disease (III and IV) constituted 36%. Treatment groups include chemotherapy alone (29%), radiation alone (10%), combined modality therapy (CMT-chemoradiation) (42%). The median overall survival (OS) for the whole cohort was 27 months (95% CI 20.6-33.7). Median OS was better in patients with early stage compared to advanced stage disease (90 vs. 6 months, P < 0.001). Among therapeutic groups in early-stage disease, CMT (N = 616) had significantly better median OS than radiation alone (N = 152) or chemotherapy alone (N = 168) (194 vs. 34 vs. 14 months, P < 0.001). No significant difference was seen between radiation alone and chemotherapy alone (P = 0.617). Among patients treated with CMT, chemotherapy-first CMT (N = 134) had better OS than radiation-first CMT (N = 347) (median OS not reached vs. 194 months, P = 0.017). In the advanced stage disease, chemotherapy-treated patients (N = 418) had better median OS compared to patients who did not receive chemotherapy (N = 103) (7.6 vs 1.3 months, P < 0.001). Among patients who received chemotherapy, patients consolidated with SCT (N = 59) had better median OS compared to the patients who received chemotherapy only (N = 353) (63 vs 6 months, P < 0.001) In multivariate analysis, factors associated with worse OS were age (HR 1.021 95% CI 1.015-1.026; P < 0.001) and B-symptoms (HR 1.463 95% CI 1.276-1.678; P < 0.001). Whereas factors associated with better OS were early stage (HR 0.450 95% CI 0.387-0.524, P < 0.001), radiation therapy (HR 0.526 95% CI 0.458-0.603, P < 0.001) and chemotherapy (HR 0.546 95% CI 0.473-0.630, P < 0.001). Conclusions: The study represents one of the largest studies on ENKTL in the US. Early-stage disease is highly curable with CMT with chemotherapy-first sequencing being superior to radiation-first sequencing. Advanced stage disease is associated with extremely poor prognosis overall but is associated with a significant improvement in OS with consolidative SCT with possible role of consolidative RT in advanced stage.

Pegarspargase and sintilimab for newly diagnosed, advanced stage natural killer T‐cell lymphoma, nasal type: an open‐label, single‐arm, phase 2 study

Pegarspargase and sintilimab for newly diagnosed, advanced stage natural killer T‐cell lymphoma, nasal type: an open‐label, single‐arm, phase 2 study

National population-based analysis of demographics and outcomes of patients diagnosed with extranodal NK/T-cell nasal type lymphoma in the US: Does ethnicity play a role?

e18772 Background: Extranodal Natural Killer/T-cell Lymphoma Nasal Type (ENKTL-NT) in an uncommon malignancy with rising incidence in the United States (US) despite previously being described only in Asia and Latin America (J Oral Maxillofac Pathol PMC3125667 Crit Rev Oncol Hematol PMID33493634). Although primarily occupying the nasal cavity, other locations may be affected, which makes its presentation ambiguous. Diagnosis is important as omitting radiation has been associated with detrimental survival (J Oncol Pract PMID31600462). This is the first national population-based analysis evaluating ethnic differences for Hispanics (HI) diagnosed with ENKTL-NT. Methods: Data were analyzed on ENKTL-NT patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2018. Demographic, clinical and survival patterns were analyzed. Kaplan-Meier and Cox regression analyses were used when appropriate. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. Results: 1,205 patients (HI=409, Non HI (NH)=796) were diagnosed with ENKTL-NT. Male sex predominated in both. HI were diagnosed at younger median age, 43 years (y) vs 59y in NH [p <0.001]. Most of HI and NH were whites 98% vs 58%; however, for NH other races were noted. Most of the patients were diagnosed between 2010-2014. For both, the presence of B symptoms was predominantly unknown. At diagnosis stage I was mainly for HI while unknown stage was most likely noted for NH [p = 0.013]. HI were less likely than NH to receive radiation as part of their treatment, 47% vs 57% respectively [p = 0.003]. Median survival for HI was 1.7y vs 1.2y for NH; survival probability at 2, 5 and 10y for HI corresponded to 0.467, 0.413 and 0.355, while for NH it was 0.444, 0.352 and 0.292, respectively. OS probability at 10y had no statistically significant difference [p = 0.06]. On multivariate analysis, those who were older than 80y and between 60-80y, had worse OS compared to those younger than 60y (HR 2.3 - 95% CI: 1.7 – 3 and 1.2 - 95% CI: 1 – 1.5). Regarding stage, those who were at stage III/IV had worse OS than those at early stage I/II (HR 2.4 -95% CI: 1.7 - 3.2 and HR 3.4 -95% CI: 2.7 - 4.30). Conclusions: This national population-based study identified statistical differences in HI diagnosed with ENKTL-NT. Interestingly, HI were less likely to receive radiation therapy which is the mainstay treatment and key determinant for survival. The fact that there was no statistical difference in survival for HI and NH may underrepresent the improved survival from HI as they are not optimally treated and still living as longer as the NH. Additional research with biological variables should be carried out to better understand this oncological outcome and potentially offer improved targeted treatments for this ethnic minority.

Peripheral T-cell lymphoma mimicking granulomatosis with polyangiitis.

Upper respiratory tract involvement is common in patients with granulomatosis with polyangiitis (GPA), but malignancies should be kept in mind in the differential diagnosis. A68-year-old man was referred to rheumatology to investigate for GPA after nasal excisional biopsy. After careful radiologic and pathologic assessment, he was diagnosed with peripheral T‑cell lymphoma, nasal type. This is arare case of T‑cell lymphoma in apatient who was referred as GPA.

Case report of extranodal natural killer/T-cell lymphoma that induced secondary hemophagocytic syndrome-related histiocytic glomerulopathy

Hemophagocytic syndrome (HPS) is a proliferative disease of the mononuclear macrophage system involving multiple organs and systems. We report a 50-year-old Asian woman who presented with unexplained fever and proteinuria. Laboratory tests showed cytopenia, considerably elevated serum ferritin and IL-2 receptor concentrations, and evidence of hemophagocytosis in the bone marrow. A renal biopsy showed macrophage infiltration into the glomerulus, resulting in podocyte and endothelial cell damage. We finally diagnosed the patient with extranodal natural killer/T-cell lymphoma, nasal type that induced HPS-related histiocytic glomerulopathy. Proteinuria and inflammation responded to treatment with high-dose pulsed methylprednisolone combined with VP-16 and cyclosporine. To the best of our knowledge, this is the first documented case of HPS-related histiocytic glomerulopathy triggered by a malignant tumor.

Research Progress of Hydrogen on Chronic Nasal Inflammation.

Chronic nasal mucosal inflammatory disease is a common nasal disease, which is involved by inflammatory cells and a variety of cytokines. Its main pathological features are inflammatory reaction, increased secretion, mucosal swelling and thickening of nasal cavity or paranasal sinuses.It mainly includes chronic rhinitis (divided into allergic rhinitis, non-allergic rhinitis), chronic sinusitis (divided into with nasal polyps, without nasal polyps type), etc.The main symptoms of chronic rhinitis are nasal itching, sneezing, runny nose, and nasal congestion. The main symptoms of chronic sinusitis are nasal congestion, purulent or sticky nasal discharge, headache, and reduced sense of smell. They are a type of disease with a high incidence rate and seriously affect the quality of human life.Although the etiology and treatment of this type of disease have been extensively studied, there are still many aspects that are unclear.Currently, oxidative stress is believed to be an important link in the pathogenesis of chronic inflammatory diseases of the nasal mucosa. Therefore, anti-oxidative stress is a direction of research for the treatment of chronic nasal mucosal inflammatory diseases.Hydrogen, as a medically therapeutic gas, has been extensively studied for its antioxidant, anti-inflammatory, and anti-damage properties, and has been used in the treatment of various diseases.Although there are relatively few studies on the use of hydrogen for nasal inflammation, its positive effects have also been found. This article systematically summarizes the relevant research on the use of hydrogen to improve chronic nasal mucosal inflammation, with the aim of clarifying the ideas and indicating the direction for further research in the future.

Respiratory Syncytial Virus-Load Kinetics and Clinical Course of Acute Bronchiolitis in Hospitalized Infants: Interim Results and Review of the Literature.

Respiratory Syncytial Virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. The role of RSV load in disease severity is still debated. We present the interim results of a prospective monocentric study enrolling previously healthy infants hospitalized for RSV bronchiolitis, collecting nasopharyngeal aspirates every 48 h from admission to discharge, and evaluating RSV load dynamics in relation to clinical outcome measures of bronchiolitis severity, including: need, type and duration of oxygen therapy, length of hospitalization, and the bronchiolitis clinical score calculated at admission. The results showed that the highest viral replication occurs within the first 48 hours after admission, with a significant decrease at subsequent time points (p < 0.0001). Moreover, higher RSV-RNA values were associated with the need for oxygen therapy (p = 0.03), particularly high-flow nasal cannula type (p = 0.04), and longer duration of respiratory support (p = 0.04). Finally, higher RSV load values were correlated with lower white blood cells, especially lymphocyte counts and C-reactive protein levels (p = 0.03, p = 0.04, and p = 0.01, respectively), as well as with patients of a younger age (p = 0.02). These data suggest that RSV may actively contribute to the clinical severity of bronchiolitis, together with other potential non-viral factors.

Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination.

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.

Primary lacrimal sac lymphoma: a case-based retrospective study in a Chinese population.

To determine the clinical characteristics, pathological types, tumor markers, treatments, and outcomes of Chinese patients with primary lacrimal sac lymphoma. This case-based retrospective study analyzed 15 Chinese patients with primary lacrimal sac lymphoma. The clinical data collected included gender, age at diagnosis, symptoms, imaging examination results, pathologic diagnosis, pathogen identification, tumor markers, treatments, follow-up, and prognosis. Descriptive statistics were used to characterize the patients. Progression-free survival (PFS) was defined as the time from surgery to the last follow-up, first record of tumor recurrence, or death. There were 7 males and 8 females with unilateral primary lacrimal sac lymphoma in the left eye (n=6) or right eye (n=9). The initial symptom in 13 patients was epiphora, and 2 patients had redness and swelling in the lacrimal sac area. All patients ultimately developed epiphora, and 12 had masses in the lacrimal sac area. Analysis of preoperative plasma tumor markers indicated 14 patients had elevated homocysteine, 9 had elevated β2-microglobulin, and 2 had elevated lactate dehydrogenase (LDH); 2 patients had elevations of all three markers, and 1 patient had no elevation of any marker. All patients underwent surgical resection and 12 patients received postoperative chemotherapy. The pathological types were DLBCL (n=8), MALT lymphoma (n=5), and NK/T-cell lymphoma, nasal type (n=2). The mean follow-up time was 25.8mo (range: 4-41) and 2 patients died. Seven patients who underwent mass excision combined with dacryocystorhinostomy (DCR) had no postoperative epiphora. Eight patients who only underwent mass excision had varying degrees of postoperative epiphora. Preoperative LDH elevation and NK/T-cell lymphoma, nasal type were associated with poor prognoses. Early diagnosis and treatment can lead to a good prognosis for most patients with primary lacrimal sac lymphoma. Mass resection combined with DCR can reduce the occurrence of post-surgical epiphora. The pathology type and tumor marker status are associated with prognosis.

Etoposide, dexamethasone, and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma: A randomized phase III study

Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200mg orally, and dexamethasone 40mg orally on days 2-4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200mg orally, and dexamethasone 40mg orally on days 2-4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was -10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n= 125] or MESA [n= 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9-93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8-91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, -5.6-10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

Branching Patterns and Variations of Facial Artery and Clinical Importance: A Cadaveric Study

Introduction: The facial artery (FA) was observed with distinctive variations and anomalous, which occur during the embryological developmental process due to the ablation of neural crest cells that impact embryonic aortic arch vessels, resulting in distinctive branching patterns. Therefore, this study aimed to investigate the types, clinical importance, localization, and differences of FA in fixed cadavers according to gender and body side. Methods: The current study was conducted on 19 formalin-fixed cadavers (68.4% males, n = 13; 31.6% females, n = 6). The types, variations, prevalence, and distance to nearby surgical landmarks of FA were recorded on both sides. Measurements were taken with a surgical microscope (Zeiss Meditec, Berlin, Germany) and a digital caliper (INCA, DCLA-0605, 0.6–150 mm). Results: Angular type % 73.1 (n = 14, right; n = 19, left), labial type % 5.3 (n = 1, right), alar type % 5.3 (n = 1, right), and nasal type % 5.3 (n = 1, right) were detected. The following parameters were significant according to gender; the distance between the ala of the nose and the origin of the FA on both sides (p = 0.007 right; p = 0.018 left), the diameter of FA at the cheilion (p = 0.019 left), diameters of the superior and inferior labial arteries at their origin (p = 0.031 right; p = 0.025 right) and PO lines. Conclusion: The significant differences in gender according to the distance of the FA and its branches from the origin should be considered to reduce complications during surgery. The differences in studies according to the types and variations of FA may be due to the scale of the study, gender, or study design.