Weekly as Opposed to Bi-Weekly Bortezomib as Part of Induction Chemotherapy in Newly Diagnosed Multiple Myeloma is Better Tolerated and Equally Efficient in Terms of Initial Therapeutic Response: Real-World Data from a Retrospective Audit

Bortezomib is a proteasome inhibitor that has shown efficacy in the treatment of newly diagnosed multiple myeloma. The VTD (Bortezomib, Thalidomide, Dexamethasone) triplet chemotherapy regime is frequently used as induction prior to autologous stem cell transplant, in line with national and international recommendations. The manufacturer’s protocol for Bortezomib recommend a twice weekly dosing schedule. Adverse effects are common, most notably peripheral and autonomic neuropathy. These adverse effects can be disabling, even at lower grades and often limit drug tolerance. We propose a once weekly Bortezomib treatment regime as an alternate modus operandi. Here we use real-world data to demonstrate that weekly compared to bi-weekly Bortezomib is better tolerated whilst achieving similar outcomes in terms of initial therapeutic response. We demonstrate a trend of lower incidence of neuropathy- both peripheral and autonomic- with the weekly regime. There was also a trend of fewer serious adverse events with the weekly regime with lower rates of hospital admissions due to infections. In addition, we show that this regime is associated with better Thalidomide tolerance. We believe that delivery of Bortezomib through a weekly regime facilitates patients being able to maintain on Bortezomib longer and receive higher cumulative doses.

Pediatric Acute Promyelocytic Leukemia

A previously healthy 4-year-old boy presented to the pediatric emergency department with high fever, headache, asthenia and neutropenia. The fever started two days prior along with the appearance of purple skin lesions. Laboratory results were as follows: White Blood Cell (WBC) count of 44.2 × 109 hemoglobin 62g/L; hematocrit 18.9%, platelet count 30 × 109/l, international normalized ratio (INR) 1.06, lactate dehydrogenase (LDH) 479u/l, creatinine 37μmol/l. Peripheral blood smear demonstrated: 80% of abnormal promyelocytes with bilobar nuclei and cytoplasmic granules; some contained multiple Auer rods. Immunophenotyping demonstrates CD13, CD33, CD117, and myeloperoxidase positivity with a high side-scatter. Fluorescence in situ hybridization revealed the t(15;17) (q22;q21.1) (PML-RARA) (Figure 1 and 2).

Prognostic Value of CD10 among Tunisian Patients with Nasopharyngeal Carcinoma

Introduction: CD10 expression was identified as a marker of poor prognosis in several types of cancer. However, its impact on the survival of Tunisian NPC patients has not been discussed. So, our objective was to confirm the prognostic value of this marker, in addition to its relationship to clinicopathologic parameters. Materials and Methods: Imunohistochemistry method was performed on formalin-fixed paraffin-embedded sections of 66 cases of NPC, 6 patients with inflammatory nasopharynx and 20 normal mucosa tissues. Results: CD10 expression was detected in 66.66 % of the NPC with predominant staining in stromal cells (81.81%). While, no expression of CD10 was noted in control group (inflammatory nasopharyngeal lesions and normal nasopharynx mucosa). CD10 positive cases were correlated with increasing tumor size (p=0.001) and lymph node metastasis (p=0.034). Furthermore, with the Kaplan-Meier test, a strong association was observed between the expression of CD10 and the recurrence status (p = 0.003). Multivariate Cox proportional hazard regression analysis showed that CD10 and lymph node metastasis factors were independent predictors of time to recurrence among NPC patients with respectively p=0.001 and p=0.044. Conclusion: The present study confirms the prognostic value of CD10 expression and suggests its strong effect on aggressive behavior of nasopharyngeal carcinoma.

The Relationship between Use of Low Molecular Weight Heparin during Pregnancy and Risk of Peripartum Adverse Events: A Meta-Analysis

Introduction: To summarize the trials investigated on relationship between low molecular weight heparin use during pregnancy and peripartum adverse events. Meta-analysis was performed to evaluate the effect of Low Molecular Weight Heparin (LMWH) on maternal and fetal complications. Methods: Electronic research was performed in Cochrane Library, MEDLINE and EMBASE through October 2020. The primary outcome was the incidence of maternal and fetal complications during peripartum period. RevMan 5.3 was used for data analysis. Results: 11 articles were finally included. Meta-analysis showed there was no significant difference in abortion, premature delivery, stillbirth, preeclampsia and postpartum hemorrhage events between pregnant women who used LMWH and those who not. Conclusion: Using LMWH in pregnant women does not increase pregnancy related maternal and fetal complications.

Study on Anti-Inflammatory Activity of Niloticin by Targeting MD-2 Based on Computer-Aided Drug Design and Biolayer Interferometry

Niloticin is an active compound from Cortex phellodendri, but its antiinflammatory activity has not yet been explored. The aim of the present study was to assess the drug potential of niloticin and to study the MD-2-targeting mechanism of its anti-inflammatory activity. Niloticin’s drug potential was analyzed using the Traditional Chinese Medicine Systems Pharmacology Database. Molecular docking and biolayer interferometry technology were used to explore the anti-inflammatory mechanism of niloticin by targeting myeloid differentiation protein 2 (MD-2), which mediates a series of Toll-Like Receptor (TLR) 4-dependent inflammatory responses. The cytokines involved in the LPSTLR4/ MD-2-NF-κB pathway were evaluated by ELISA, RT-PCR, and western blot. The results showed that niloticin has drug potential and could bind to MD- 2. Niloticin had no impact on cell viability. Niloticin could significantly decrease the levels of NO, IL-6, TNF-a, and IL-1β (P<0.01) induced by LPS. IL-1β, IL-6, iNOS, TNF-a, and COX-2 mRNA expression levels were decreased by niloticin (all P<0.01). Compared with the control group, TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all P<0.01). In conclusion, niloticin is a potential MD-2 antagonist. It might interact with MD-2 to play an anti-inflammatory role by suppressing the activation of the LPS-TLR4/MD-2-NF-κB signaling pathway.

Pancreatic Origin Hepatoid Adenocarcinoma with Liver Metastasis

Hepatoid Adenocarcinoma (HAC) is a rare form of aggressive extrahepatic neoplasm with similar morphologic features to Hepatocellular Carcinoma (HCC). HAC with pancreatic origin is rare and the exact incidence is unknown. Given shared morphological and Immunohistochemical (IHC) characteristics, it may be difficult to distinguish metastatic HAC with liver involvement from primary HCC. We present a rare case of ductal type pancreatic hepatoid adenocarcinoma involving the pancreatic head, ampulla of Vater, and liver, and illustrate strategies for diagnosis and treatment. A 65-year-old woman presented with epigastric pain, vomiting, melena, and weight loss. There was direct hyperbilirubinemia with elevated hepatic markers. Imaging displayed a pancreatic head mass with moderate biliary obstruction and a hepatic lobe lesion. Fine needle biopsy of the liver mass initially was consistent with HCC, and biopsies of the pancreatic mass and ampulla walls showed pancreatic adenocarcinoma. Due to the unusual finding of co-existing HCC and pancreatic adenocarcinoma, the hepatic mass biopsy was sent for external evaluation, which revealed poorly differentiated adenocarcinoma, consistent with HAC of pancreatic origin. The tumor was positive for mucicarmine stain, HepPar1, CEA, and CK7. It was negative for MOC-31, Arginase, ALBISH, MGB, ER, TTF-1, GCDFP15, CK-20 and CDX2, thus confirming HAC. The patient was referred to outpatient chemotherapy with gemcitabine and paclitaxel however demonstrated progression and expired following recurrent bilateral pulmonary emboli. HAC may present with non-specific symptoms, is highly aggressive, and may be difficult to distinguish from primary HCC from histopathologic characteristics alone. Accurate diagnosis requires clinicohistopathologic and IHC analysis.

The Usefulness of Diagnostic Vitrectomy in Neoplastic and Non-Neoplastic Masquerade Syndrome: An Observational Study

Introduction: Masquerade intraocular inflammation may be considered neoplastic or non- neoplastic masquerades such as primary intraocular lymphoma, leukemia, infectious and inflammatory diseases. These pathologies require a definitive diagnosis, as the treatment modalities are different. The aim of our study was to investigate the safety and usefulness of diagnostic vitrectomy with vitreous humor flow cytometry in eyes with intraocular inflammation of unknown etiology. Methods: A retrospective observational study included 35 eyes of 29 patients with atypical intraocular inflammation unresponsive to corticosteroid therapy. In all cases diagnostic vitrectomy with flow cytometry analysis of the vitreous specimen was performed. Results: Among 35 eyes, the result of diagnostic vitrectomy analysis showed unspecific inflammatory response in 7 (20.0%) eyes, confirmed neoplastic diseases in 5 (14.3%) eyes. All of them it was intraocular lymphoma but one of the eyes with primarily diagnosed lymphoma and one of the eyes with primarily diagnosed unspecific inflammatory response in flow cytometry has been diagnosed finally as a choroidal melanoma after enucleation of the eyeball. Diagnostic vitrectomy excluded neoplastic disease in 7 eyes (20.0%). In 3 eyes (8.6%) bacterial infection, in 4 eyes (11.4%) viral infection. In 2 eyes (5.7%) we excluded bacterial infection, in 7 cases (20.0%) no conclusive results were obtained. The most common adverse event was cataract in patients (12 eyes, 34.3%). Conclusion: Diagnostic vitrectomy with flow cytometry of vitreous humor is helpful in confirming the clinical suspected diagnosis of posterior segment inflammation. Flow cytometry need to be complemented with other diagnostic test including cytopathology, especially in cases suspected of intraocular lymphoma. Flow cytometry of the vitreous humor in choroidal melanoma is not a useful diagnostic tool.

AML with Renal Infiltration Manifesting as Acute Renal Failure, Diagnosed with FDG-PET CT Scan: Case Report

Extramedullary disease in acute myeloid leukemia is a known phenomenon with reported incidence of 2.5-9.1 %. However, acute kidney injury due to direct infiltration of malignant cells is reported in only 1% cases of acute leukemia. We report a case of acute myeloid leukemia who developed acute kidney failure at presentation, was diagnosed with renal and pancreatic infiltration by FDG-PET scan and was treated successfully with hypomethylating agent and venetoclax. PET-CT scan can be a non-invasive modality for diagnosing extramedullary disease in acute myeloid leukemia and monitoring of response to therapy in these cases. Early initiation of anti-leukemia therapy in our case lead to complete metabolic response with normalization of the renal functions.

Efficacy and Side Effects in HER2-Positive Advanced Breast Cancer Patients Treated with Pyrrotinib: A Real-World Study in China

Background: Pyrotinib is a molecular and irreversible tyrosine kinase inhibitor independently developed in China, and its efficacy against HER2- positive breast cancer in the real world is not clear. In this study, we evaluated the efficacy and safety of pyrotinib in the treatment of HER2-positive advanced breast cancer based on real-world evidence. Materials and Methods: We designed a prospective observational study. Thirty-six patients with HER2-positive advanced breast cancer from a single medical center were included in the study from December 2018 to February 2021. All patients received the oral HER2 receptor inhibitor pyrotinib and received concurrent chemotherapy or endocrinotherapy. The follow-up endpoint is set as April 1, 2021. The primary endpoint is Objective Response Rate (ORR) and Disease Control Rate (DCR), and the secondary endpoint is Progression- Free Survival (PFS) and related side effects. Results: By the end point of follow-up, a total of 17 patients had progressed (including 6 deaths), and the progression-free survival rate was 52.78%. The median PFS was 13months (PFS range: 3-22 months). As the best response, 4 patients achieved CR, 20 patients achieved PR, 9 patients achieved SD, and 3 patient developed PD. The ORR was 66.67% and DCR was 91.67%. In the analysis, first-line pyrotinib treatment appeared to have higher ORR (88.88% vs 59.26%), but there was no significant difference. In addition, pyrotinib showed significant efficacy in patients with brain metastases, with an ORR of 42.85%. In terms of safety, the incidence of diarrhea was 80.55%, but only 4 patients had grade 3 diarrhea, which was tolerable after the drug dose was reduced; 1 patient had grade 4 neutropenia and grade 3 and thrombocytopenia, which were considered to be related to the chemotherapy drugs. The incidence of other adverse reactions was low, and all were grade 1 to 2. Conclusion: Pyrotinib combined with chemotherapy has a significant effect on HER2-positive breast cancer, and there is still a high ORR in patients who fail multiple lines of treatment. Side effects are overall controllable and safe.

Vanishing Bile Duct Syndrome and Hodgkin’s Lymphoma: Case Report and Thorough Review of the Literature

Vanishing Bile Duct Syndrome (VBDS) is a rare, acquired disorder, characterized by progressive destruction and loss of intrahepatic bile ducts. The main clinical manifestations are jaundice and pruritus, caused by intralobular cholestasis. Although the pathogenic mechanism is poorly understood, VBDS has been associated with numerous etiologies such as medications, malignancies, infections and autoimmune diseases. This syndrome can appear as a paraneoplastic phenomenon in patients with Hodgkin’s Lymphoma (HL). Diagnosis is based on clinical evaluation and confirmed via liver biopsy, while treating the underlying cause is the main therapeutic target. If bile duct regeneration does not occur, possible outcomes include cirrhosis, hepatic failure and death, with liver transplantation being the only curative option. In this paper, we describe a case of HL-related VBDS in a 31-year-old female patient, who presented with jaundice, pruritus and cervical lymphadenopathy. The stage of HL was determined as IIA and a liver biopsy was performed, which confirmed the degeneration of bile ducts. The patient was treated with the ABVD regimen and dexamethasone. Follow-up tests were normal and supported the full remission hypothesis. We conducted an analytical literature review and collected the available data from 38 confirmed cases, regarding the epidemiology, viral infections, clinical findings, therapeutic options and outcome.