The role of chidamide in the treatment of B-cell non-Hodgkin lymphoma: An updated systematic review.

B-cell non-Hodgkin lymphoma (B-NHL) is a lymphoid malignancy derived from B-cells that remains difficult to treat. Moreover, relapses and refractory cases are common. Abnormalities in epigenetic mechanisms, such as imbalanced histone acetylation affecting certain genes, contribute to relapses and refractory cases. Chidamide (tucidinostat) is a novel histone deacetylase inhibitor that can reverse this epigenetic imbalance and has been approved for the treatment of T-cell malignancies. However, the use of chidamide for B-NHL remains limited, and the lack of relevant literature exacerbates this limitation. We conducted this review to summarize the anticancer activity of chidamide against B-NHL and its clinical applications to overcome drug resistance. This systematic review was conducted according to the PRISMA 2020 guidelines, using some keyword combinations from MEDLINE and EBSCO. The inclusion and exclusion criteria were also defined. Of the 131 records retrieved from databases, 16 were included in the review. Nine articles revealed that chidamide limited tumor progression by modifying the tumor microenvironment, stopping the cell cycle, inducing apoptosis and autophagy, and enhancing complement-dependent and antibody-dependent cell-mediated cytotoxicities.According to seven other studies, administering chidamide in combination with another existing therapeutic regimen may benefit not only patients with relapsed/refractory B-NHL, but also those with newly diagnosed B-NHL. Chidamide plays many important roles in limiting B-NHL progression through epigenetic modifications. Thus, combining chidamide with other anticancer drugs may be more beneficial for patients with newly diagnosed and relapsed/refractory B-NHL.

Comparison of Extravillous Intermediate Trophoblast Invasion Depth and Distribution Pattern Between Placenta Accreta and Non-Accreta.

BACKGROUND Placenta accreta spectrum (PAS) is a complex obstetric complication that poses a major risk for life-threatening hemorrhage. The pathogenesis of PAS is known to be related to placentogenesis, trophoblastic cells invasion, and previous obstetrical procedures that cause uterine wall defects. However, the precise mechanism of this disease has not been fully explained. This study aimed to evaluate the differences in maximum depth of invasion and distribution pattern of implantation site intermediate trophoblasts between PAS and non-accreta cases. MATERIAL AND METHODS This was an observational, analytic, cross-sectional study that utilized paraffin block specimen of peripartum hysterectomy performed in Hasan Sadikin General Hospital Bandung from 2018 to 2020. Sixty-four samples were obtained, then classified as PAS and non-accreta (normal placenta). Implantation site-intermediate trophoblasts were identified using CD-146 staining. Maximum invasion depth of intermediate trophoblasts was measured in micrometers, while the distribution pattern was assessed and classified into 2 groups: confluent and scattered. RESULTS We found that the maximum invasion depth of the intermediate trophoblasts was significantly higher in the PAS group compared to that of the non-accreta group (2453.52±1172.122 µm vs 1613.59±822.588 µm, P=0.009). The confluent distribution pattern was significantly more common in the PAS group compared to that of the non-accreta group (87.2% vs 17.6%, P=0.0001). CONCLUSIONS The findings of our study suggested that implantation site intermediate trophoblasts play a role in the pathophysiology of placenta accreta. Further studies are needed to determine factors that affect trophoblast invasion leading to placenta accreta spectrum.

Case of metachronous clear cell bladder metastasis on low risk localized renal cell carcinoma patient.

INTRODUCTION: Renal cell carcinoma (RCC) is well known for its ability to metastasize into different organs. However, the management of metachronous RCC is still not yet standardized. CASE PRESENTATION: A 62 years old man was presented with haematuria for the last 2 months. CT scan revealed bladder mass with a size of 2,5 cm and underwent en-bloc resection of bladder mass. The histopathological result showed non-muscle-invasive bladder clear cell renal carcinoma. The patient had a history of left nephrectomy in 2017 and meningioma mass metastasectomy in 2020 with the same histopathological origin. CONCLUSION: Bladder metastasis of RCC can be treated by endoscopic surgical intervention.

Polyorchidism and testicular malignancy, what can we learn: A case report.

INTRODUCTION: Polyorchidism is a rare condition with a total number of approximately 190 cases. Malignancy was found in 6,4% of cases. CASE PRESENTATION: A 57 years old man came with a sudden and persistent painful mass in right inguinal region. The patient decided to undergo surgery with diagnosis of incarserated lateral hernia inguinal and obtained a testicular-like lump in the right inguinal canal, then the patient underwent orchiectomy. Histopathological examination revealed a soft tissue tumor with microscopic characteristic of seminoma. CT-Scan revealed metastasis to lung and liver. CONCLUSION: Attention must be given to detect malignancy in polyorchidism.

Analysis of Mutant Isocitrate Dehydrogenase 1 Immunoexpression, Ki-67 and Programmed Death Ligand 1 in Diffuse Astrocytic Tumours : Study of Single Center in Bandung, Indonesia.

OBJECTIVE: Diffuse astrocytic tumour (DAT) is a diffuse infiltrative astrocytoma tumour accompanied by molecular parameters such as the presence or absence of isocitrate dehydrogenase (IDH) gene mutations. Ki-67 is a marker for DAT proliferation, while programmed death ligand 1 (PD-L1) indicates an immune evasion mechanism. This study aimed to analyze the correlation among mutant IDH1 R132H, Ki-67, and PD-L1 immunoexpression in the DAT. METHODS: A cross-sectional study was carried out on 30 paraffin blocks of DAT cases. Paraffin block samples consist of grade II (n=14), grade III (n=8), and grade IV (n=8). In this study, the immunohistochemistry-staining of mutant IDH1 R132H, Ki-67, and PD-L1 were carried out to determine the frequency of DAT with IDH1 mutations. RESULTS: Our study shown the frequency of IDH1 mutations in grade II 50.0% (7/14), grade III 37.5% (3/8), and grade IV 12.5% (1/8). Our study also showed a difference in Ki-67 and PD-L1 expression between each the degree of DAT histopathology (p=0.0001 and p=0.002, respectively). There was an association between both mutant IDH1 R132H, and Ki-67 with PD-L1 expression in DAT (p=0.0087 and p=0.0049, respectively). CONCLUSION: DAT with the mutant IDH1 is frequently observed in grade II and small number of grade III. The expression of wild type IDH1, Ki-67, and PD-L1 were found to be higher in high grade DAT (grade III and grade IV). There is a correlation between each of mutant IDH1 status and Ki-67 with PD-L1 expression in DAT.

Detection of endometriosis using immunocytochemistry of P450 Aromatase expressions in eutopic endometrial cells obtained from menstrual sloughing: a diagnostic study.

OBJECTIVE: To explore the possibility of a new diagnostic approach of endometriosis based on immunocytochemistry scoring of Aromatase P450 expressions in endometrial cells collected from menstrual sloughing. This is a case control study. Immuncytochemistry scores vs. histopathological examination in one tertiary- and secondary-level hospital in Bandung; two secondary level hospital in Garut and Sumedang, West Java, Indonesia. Thirty-five patients with and without endometriosis were enrolled. All subjects had diagnostic procedures for endometriosis suspicion, with addition menstrual blood samples for cytopathological examination. The specimens were sent for immunocytochemistry assessment of P450 Aromatase expressions (ICAPEC). The previous procedure resulted in cut-off point of histo score (H-score), sensitivity, specificity, (+) and (-) ICAPEC predictive value. RESULTS: The P450 Aromatase expression in endometrial cells of women with endometriosis was significantly stronger than without one. The cut-off point of H-scores to detect endometriosis was > 4. By this criteria, H-score had 94.6% sensitivity, 90.9% specificity, 92% positive predictive value and 93% negative predictive value. Immunocytochemistry scoring of Aromatase P450 expression in endometrial cells (ICAPEC) derived from menstrual blood specimen was a good candidate as alternatives approach in diagnostic procedure of endometriosis. Application and evaluation in clinical practice would provide the economically benefit in diagnostic procedure.

Low-Stage Gastric MALT Lymphoma Causing Life-Threatening Upper Gastrointestinal Bleeding.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is an uncommon tumor of the stomach that only comprises around 1-6% of all tumors of the stomach. Non-Hodgkin lymphoma more commonly affects the lymph nodes and may spread to the spleen and bone marrow, whereas extranodal non-Hodgkin lymphoma is less common. Primary gastric lymphoma is further divided based on histologic features; one of the types is MALT lymphoma, which is strongly associated with Helicobacter pylori infection. The first sign of the disease is usually mimicking gastritis. However, in the case reported here, the first sign of gastric MALT lymphoma was massive gastrointestinal (GI) bleeding with hemodynamic instability in a 75-year-old male. The patient came to the emergency department and was immediately resuscitated, intubated, and admitted to the intensive care unit. Urgent endoscopy (<6 h) was done to identify the source of bleeding, which were oozing ulcerated polypoid masses; endoscopic hemostasis was done, which successfully stopped the bleeding. However, the next day, rebleeding occurred and a second endoscopic hemostasis was performed. The bleeding stopped and the patient showed gradual improvement. The biopsy result of a gastric MALT lymphoma of grade IE1 with H. pylori infection warranted a treatment regimen for Helicobacter eradication. The patient recovered, with follow-up endoscopy at 3 months, at 6 months, and yearly thereafter with no sign of recurrence. This case shows that gastric MALT lymphoma, even at a low stage (1E1), can cause life-threatening upper GI bleeding that requires aggressive resuscitation and urgent endoscopy.

Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer.

OBJECTIVES: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. METHODS: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. RESULTS: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). CONCLUSIONS: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

Human papillomavirus genotypes profile in cervical cancer patients at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia.

BACKGROUND: As in other developing countries, cervical cancer is the most frequent gynecologic malignancy in Indonesia. Persistent high risk genotypes of human papillomavirus (HPV) that infect the cervical tissue have been established as the etiology of cervical cancer. This study aimed to explore the profile of cervical cancer patients and the infected HPV genotypes at Dr. Hasan Sadikin General Hospital-Bandung. MATERIALS AND METHODS: During the year 2010, 554 cervical cancer patients were registered. In a subset of the patients during July-November 2010, 40 randomized fresh biopsies were tested for HPV genotype after obtained informed consent. The distribution of HPV genotypes and the association to risk factors were analysed. RESULTS: The result showed that 62.5% of the tested biopsies were infected by multiple HPV infections, with HPV-16 found in most of the cervical cancer patients (90%). Marriage at age younger than 16 years old was statistically significant in relation to multiple HPV infection (p=0.003), but not parity more than three times (p=0.59). CONCLUSIONS: Although high paritiy in our study was not associated with multiple HPV infection, good family planning programs and reproductive health education need to be emphasized in Indonesia as high parity and marriage at young age might increase the chance of cervical cancer development.