Transformation of HHV-8-negative idiopathic multicentric Castleman disease into diffuse large B-cell lymphoma: A case report from Nepal.

Key Clinical Message: Idiopathic Castleman disease transforming into Diffuse Large B-cell Lymphoma has an aggressive course and can lead to mortality. Hence, early diagnosis and intervention are required. Abstract: Idiopathic Castleman disease transforming into non-Hodgkin lymphoma has an aggressive course, poor prognosis, and high mortality rate. Hence, early diagnosis and intervention are necessary. In a developing country like Nepal, where infectious diseases, particularly TB, are high, concomitant infection worsens the disease course. It also poses a diagnostic challenge as the clinical presentation may be similar.

Multimodality treatment of a primary vulvar melanoma in a low resource setting: A case report.

Primary vulvar melanoma is a rare but highly aggressive malignant neoplasm accounting for 1-2 % of all malignant melanoma and 5-10 % of all vulvar cancers in females. Here we report a case of 32 years old female diagnosed with primary vulvar melanoma during the evaluation of a two cm growth in the inner labia minora on the right side. She underwent wide local excision with excision of the distal one cm of the urethra and bilateral groin node dissection. The final histopathology was vulvar malignant melanoma with 1 out of 15 groin nodes involved but all resected margins were free of tumor. The final surgical stage was T4bN1aM0 (8th AJCC TNM) and IIIC (FIGO). She received adjuvant radiotherapy followed by 17 cycles of Pembrolizumab. To date, she is both clinically and radiologically disease free with a progression-free survival of 9 months.

Primary adrenocortical carcinoma: a case report.

Adrenal tumors are very common, affecting 3-10% of the human population, and most are small, benign, nonfunctional adrenocortical adenomas. Adrenocortical carcinoma (ACC), in contrast, is a very rare disease. The median age of diagnosis is in the fifth to sixth decade. There is a predilection for the female gender (the ratio of female to male ranges from 1.5 to 2.5 : 1) the adult. Case presentation: A 28-year-old man who had no prior history of systemic hypertension or diabetes mellitus presented with bilateral limb swelling for 2 months and facial puffiness for 1 month. He had an episode of hypertensive emergencies. A radiological and hormonal work-up established the diagnosis of primary ACC. One cycle of chemotherapy was given until he lost follow-up and succumbed to death due to financial constraints. Conclusions: Adrenocortical carcinoma is an extremely uncommon tumor of the adrenal gland, and it is even more uncommon when it manifests without any symptoms. If patients exhibit signs of rapid and multiple adrenocortical hormone excess, such as weakness, hypokalaemia, or hypertension, ACC may be suspected. Recently developed gynecomastia in men may be brought on by an ACC producing too much sex hormone. To accurately diagnose the condition and give the patient a fair prognosis, a multidisciplinary approach involving endocrine surgeons, oncologists, radiologists, and internists is advised. Proper genetic counseling is recommended. It is critical to know whether the adrenal mass is malignant or not, and to get this ascertained by a computed tomography finding and biopsy.

Leukemoid reaction in a patient with metastatic renal cell carcinoma-rare clinical presentation seen in Nepal: a case report.

Leukemoid reaction (increase in leucocyte count >50 ×109 cell/l) occurs due to reactive causes of bone marrow and is diagnosed after excluding the malignant haematological disorder. Leukemoid reaction is a rare clinical presentation in metastatic renal cell carcinoma and is said to have a rare prognosis. This case has had been reported in the line of SCARE criteria. Case presentation: A case of a 35-year-old female with no known previous co-morbidities presented with a history of abdominal pain in the right flank region for 2 months, fever and cough for 2 months. Physical examination showed palpable mass and tenderness in the right flank and investigations showed leukemoid reaction in peripheral blood smear. The patient was initially treated with strong intravenous antibiotics with suspicion of pyelonephritis in another centre, despite which the patient still had elevated leucocyte count and referred to our centre, where the patient was evaluated for elevated leucocyte count and with further investigations, ruled out any malignant haematological disorder. Final diagnosis of renal cell carcinoma was made by renal mass biopsy. The patient underwent targeted therapy with sunitinib. The patient expired and further investigation and follow-up were not possible. Conclusion: The lack of data and evidence of extensive diagnostic tests is the reason we are unable to assume leukemoid reaction as a poor prognostic factor in case of metastatic renal cell carcinoma. The presence of other paraneoplastic syndromes with renal cell carcinoma might have resulted in the poor prognosis that cannot be excluded.

Outcome of Epidermal Growth Factor Receptor Mutated and Non Mutated Adenocarcinoma Lung to Standard Therapy.

BACKGROUND: Asian patients with adenocarcinoma of lung have higher incidence of epidermal growth factor receptor mutations which predict increased response and survival in patients to oral tyrosine kinase inhibitors. This study was conducted to study the frequency of epidermal growth factor receptor mutation in patients in Nepal and compare the outcome in epidermal growth factor receptor mutated versus non-mutated patients receiving standard therapy. METHODS: This is an observational study conducted among newly diagnosed patients with stage IV adenocarcinoma of lung in Bir Hospital from April 2017 to June 2018. Demographic and clinical data collection along with epidermal growth factor receptor mutation testing was done. Patients with epidermal growth factor receptor mutations received Gefitinib while non-mutated patients received systemic chemotherapy. Response evaluation, progression free survival at 1 year, objective response rate and quality of life were compared. Follow up period was for 1 year. RESULTS: Eighty three (33%, n=253) patients were diagnosed with adenocarcinoma of the lung with mean age at diagnosis being 59.4 years. epidermal growth factor receptor mutations were found in 29% patients. Complete response was achieved in 9.1% vs 3.0 % (p=0.46), objective response rate was 27.3% versus 15.2% (p=0.23), progression free survival at 1 year was 39% vs 27%, (p = 0.29) and mean score of global health status was 68.1 versus 61.6 in epidermal growth factor receptor mutated versus non-mutated (p = 0.036). CONCLUSIONS: The frequency of epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung was lower than in Eastern Asian studies, but higher than in western populations. epidermal growth factor receptor mutated patients had improved survival, better treatment response and quality of life in comparison with non-mutated.

Building a 'Virtual Library': continuing a global collaboration to strengthen research capacity within Nepal and other low- and middle-income countries.

To fill the gap in health research capacity-building efforts, we created the 'Virtual Library' (VL) - a web-based repository of context-relevant resources for health researchers in low- and middle-income countries (LMICs). This paper describes the participatory process used to systematically develop the VL, and describes how our interprofessional team - representing both an LMIC (Nepal) and a high-income country (HIC) (USA, US) - engaged in shared meaning-making. A team of researchers and clinicians representing a range of subdisciplines from Nepal and the US created a replicable search strategy and standardized Resource Screening Guide (RSG) to systematically assess resources to be included within the VL. Descriptive methods were used to summarize findings from the RSG and lessons learned from the collaborative process. Collectively, 14 team members reviewed 564 potential resources (mean = 40, SD = 22.7). Mean RSG score was 7.02/10 (SD = 2). More than 76% of resources met each of the four quality criteria (relevant; reputable, accessible; understandable). Within the published VL, 298 resources were included, organized by 15 topics and 45 sub-topics. Of these, 223 resources were evaluated by the RSG; 75 were identified by team member expertise. The collaborative process involved regular meetings, iterative document revisions, and peer review. Resource quality was better than expected, perhaps because best practices/principles related to health research are universally relevant, regardless of context. While the RSG was essential to systematize our search and ensure reproducibility, team member expertise was valuable. Pairing team members during peer-review led to bi-directional knowledge sharing and was particularly successful. This work reflects a highly collaborative global partnership and offers a model for future health research capacity-building efforts. We invite engagement with the Virtual Library as one supportive pillar of infrastructure to develop individual and institutional research capacity.

Plasmablastic lymphoma of the colon in HIV negative patient; a case report with literature review.

Introduction: Plasmablastic lymphoma (PBL) is a rare and aggressive variant of diffuse large B cell lymphoma characterized by weak or absent expression of conventional B cell markers and strong expression of plasma cell markers. Very few cases of PBL of the colon have been reported in HIV negative patients. Case presentation: A 57 years female with HIV negative serology, a known case of hypertension under medication presented with right lower abdominal pain associated with vomiting and significant weight loss. On abdominal examination, soft, tender, and globular lump was palpable. Contrast enhanced computed tomography of abdomen and pelvis revealed asymmetrical enhancing mass like wall thickening involving ileocaecal region, caecum, and ascending colon, which on colonoscopy was found to be ulceroproliferative in nature. Open right hemicolectomy was performed and postoperative histopathology and immunohistochemistry results confirmed plasmablastic lymphoma as the final diagnosis. She was treated with nine cycles of chemotherapy. Clinical discussion: Although PBL is commonly found in the oral cavity, and HIV positive patients, it can rarely occur in extra-oral sites, and HIV negative patients. Due to its rarity, no optimal therapeutic approach has yet been defined for the treatment of PBL. It has a poor prognosis, and the overall survival rate has been correlated with international prognostic index score and achievement of complete remission. Conclusion: As plasmablastic lymphoma is rare and highly aggressive, its delayed diagnosis will lead to poor outcome. Thus, awareness about its clinical presentation, histopathological features, and immunophenotype is essential.

Metastases after mastectomy for ductal carcinoma in situ of the male breast; A case report.

Introduction: and importance: Male breast cancer is a rare entity. Ductal carcinoma in situ (DCIS), constituting 10% of all male breast cancer, is confined within the breast ducts and lobules, rarely metastasizing and even less so after mastectomy. Case presentation: A 71 years old male with no history of trauma presented with pain, swelling, and deformity of the left arm. He had continuous back pain for 6 months and a history of mastectomy of the right breast. Fracture of shaft of the left humerus was detected on X-ray. Computed tomography (CT) showed multiple vertebral metastases later confirmed to be metastasized from the breast by biopsy. Tumor cells were progesterone receptor (PR) positive, estrogen receptor (ER) negative, and human epidermal growth factor receptor 2 (HER2) negative. The fracture was treated and the patient was kept on Tamoxifen. On follow-up after four months, the patient is doing well with relief of back pain. Clinical discussion: Despite mastectomy and the histopathological diagnosis of pure DCIS, distant metastases can occur even in absence of locoregional recurrence. Therefore, the aggressive phenotype of DCIS rather than diagnostic or treatment variables can be thought to bring worse outcome in the form of metastases. Early hormonal status identification and hormone therapy could result in a better outcome. Conclusion: Skeletal metastases should be strongly suspected in patients presenting with bone pain and having a history of DCIS of the breast, even after mastectomy. Even though distant metastasis after mastectomy is rare, regular follow-up and surveillance is necessary.

Highlights from ecancer Choosing Wisely Nepal 2022: critical appraisal skills for evidence-based practice, 24th-25th September 2022, Kathmandu, Nepal.

The ecancer Kathmandu 2022 workshop on the 24th-25th September 2022 was the first ecancer conference organised in Nepal, a Southeast Asian nation sandwiched between India and China. It was focused on critical appraisal skills for evidence-based practice and was organised in partnership with the Karnali Academy of Health Sciences and the Civil Service Hospital from Nepal, and the Queen's Global Oncology Program from Canada. The workshop emphasised the need for critical thinking in understanding clinical research, and also motivated the delegates to undertake meaningful clinical research relevant to the local setting. The sessions highlighted the features of a good clinical research, identify pitfalls in the reporting of clinical trials, implementation of the research into locally relevant practice and development of local clinical guidelines. Furthermore, the faculty also discussed how to write a good scientific paper, the do's and don'ts of a systematic review and meta-analysis, the role of peer-review and how to do one properly and what do editors look for in evaluating papers submitted for publication. The audience learned the importance of finding a good mentor and fostering local and international collaboration. The local faculty also highlighted their own personal journeys and how mentorship and global collaboration played an important role in their own academic career. The enthusiastic panel discussion was a highlight of the programme where the delegates learned about several important topics from the faculties, such as work-life balance, the role of mentorship in building careers and building networks.

Personalized Medicine in Oncology in the Developing World: Barriers and Concepts to Improve Status Quo.

Personalized medicine (PM) has revolutionized oncology management in high human development indexed countries. By interrogating both disease and host factors through a variety of tools, oncologists have been able to better target an individual's cancer, leading to improved outcomes. But both the tools used to define these variables, such as next generation sequencing, large immunohistochemical and fluorescence in situ hybridization (FISH) panels, and the weapons employed against each target are extremely expensive. The expenses have to be measured as not only the direct cost to the patient but also the cost to the system to develop and deploy the necessary infrastructure to optimally use them. However, the concepts of predictive, timely prevention and PM have demonstrated improvement in patient's satisfaction and cost effectiveness. In this paper we will summarize the relevant barriers and challenges that limit the implementation of PM in the developing world with an emphasis on the challenges in Nigeria and Nepal.

Overview of Delivery of Cancer Care in Nepal: Current Status and Future Priorities.

Nepal is a small, low-income country between India and China with a unique health care delivery system. Cancer is becoming an important public health problem in the country, but a systematic plan to cancer control is lacking. In this article, we aim to provide a systematic assessment of the burden of disease and available resources and suggest prioritization approaches for the future to assist with any such future cancer control plans for the country.

Reliance on Self-Medication Increase Delays in Diagnosis and Management of GI Cancers: Results From Nepal.

PURPOSE: Patients with GI cancers in Nepal often present with advanced disease and poor outcomes. The purpose of the study was to determine the time to presentation, diagnosis, and treatment of GI cancer and the baseline factors that may be associated with delays. PATIENTS AND METHODS: An institutional review board-approved study was performed in Kathmandu, Nepal, from July 2018 to June 2019. Patients with newly diagnosed GI cancers were asked to fill out a standardized questionnaire. Baseline factors such as residence, literacy, and use of self-medication were recorded. Patients were asked to report the time from first symptom to presentation, time from primary care visit to pathologic diagnosis, and time from diagnosis to surgery and/or treatment. Baseline factors were analyzed using 2-tailed t tests (Prism 8.0; GraphPad, La Jolla, CA) to determine whether any factors were associated with longer time delays in these 3 intervals. RESULTS: The cohort comprised of 104 patients with a median age of 53.5 years (range, 22-77 years); 61.5% were men, 46.2% had upper GI cancers, and 83.7% presented with stage III or IV disease. The median time to presentation was 150 days, time to diagnosis was 220 days, and time to treatment was 50 days. There was no statistically significant difference in time intervals between upper and lower GI cancers. Use of self-medication (88.5%) was the only factor associated with longer time intervals to presentation, diagnosis, and treatment. CONCLUSION: Patients in Nepal have long time intervals to presentation, diagnosis, and treatment of GI cancer. Self-medication led to longer delays. Reasons for self-medication and other potential barriers will be explored in future studies in the hopes of improving outcomes.

Procalcitonin and C-Reactive Protein As Markers of Bacteremia in Patients With Febrile Neutropenia Who Receive Chemotherapy for Acute Leukemia: A Prospective Study From Nepal.

PURPOSE: The purpose of this study was to evaluate the clinical significance of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP) in patients with febrile neutropenia (FN) undergoing chemotherapy for acute leukemia. METHODS: We conducted a prospective, observational study in patients who developed FN while undergoing chemotherapy for acute leukemia. PCT and CRP were obtained in patients who presented with FN. Blood cultures also were obtained. The primary goals were to evaluate the ability of PCT and CRP to predict bacteremia in patients with FN. The secondary goals were to assess the prognostic role of PCT and CRP and to assess the microbiologic profile and culture sensitivity patterns in the study population. RESULTS: A total of 124 episodes of FN that involved 67 patients with acute leukemia occurred in the study. PCT was superior to CRP in the prediction of bacteremia. The median PCT level in the bacteremia group was 3.25 ng/mL compared with 0.51 ng/mL in the group without bacteremia (P < .01). The median values of CRP in the bacteremia and without-bacteremia groups were 119.3 mg/L and 94.5 mg/L, respectively (P = .07). There were no differences in median PCT and CRP in patients who died and those who improved. Of the 42 positive cultures, Gram-negative bacteremia was common (86%), and Escherichia coli was the most frequent organism isolated. Carbapenem resistance was seen in 39% of positive cultures. CONCLUSION: PCT is an effective biomarker to predict bacteremia in patients with FN undergoing chemotherapy for acute leukemia.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.