Introduction: Cushing’s disease (CD) in adolescents may present with subtle clinical features, resulting in a significant diagnostic challenge. We report a case of a young lady whose CD initially masqueraded as Type 2 diabetes (T2D), highlighting the difficulties in differentiating early hypercortisolism from T2D. Case: A 12-year-old female was incidentally diagnosed with diabetes during routine medical screening. Examination revealed an overweight female without the classical features of Cushing’s syndrome. Due to the presence of acanthosis nigricans, a diagnosis of T2D was initially made. Her diabetes remained well-controlled with a single oral glucose-lowering drug. The diagnostic challenge became apparent over time. She experienced delayed menarche at the age of 17, and a diagnosis of Cushing’s syndrome was suspected when she subsequently developed hypertension and reduced bone mineral density. Biochemical evaluation was consistent with adrenocorticotropic hormone (ACTH)- dependent hypercortisolism, evidenced by the failure of serum cortisol suppression on low dose and overnight dexamethasone suppression tests. Her 24-hour urinary cortisol was elevated twofold, and plasma ACTH was elevated (17.8 pmol/L). MRI demonstrated a right-sided pituitary microadenoma (0.3 × 0.5 × 0.3 cm), and inferior petrosal sinus sampling confirmed the diagnosis of CD. She underwent endoscopic transsphenoidal surgery 7 years later, which was complicated by panhypopituitarism and cranial diabetes insipidus. Postoperatively, CD was cured, with the resolution of her metabolic comorbidities. Conclusion Despite the increasing prevalence of T2D in adolescents, clinicians must recognize the diagnostic challenge of CD in this age group. Atypical manifestations in a presumed T2D patient should prompt consideration of Cushing’s syndrome.
Adolescent ; Humans ; Diabetes Mellitus, Type 2

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Objective: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

INTRODUCTION: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative option for relapse/refractory (R/R) lymphomas that have failed autologous transplantation or for high-risk lymphomas in the upfront setting. We conducted a retrospective analysis on consecutive lymphoma patients who underwent allo-HSCT over a 20-year period (2003- 2022) at Singapore General Hospital and National University Hospital Singapore. METHOD: A total of 121 patients were included in the study. Median age was 41 years. Diagnoses include Hodgkin lymphoma (HL, 15%), B-cell non- Hodgkin lymphoma (B-NHL, 34%), T-cell non-Hodgkin lymphoma (T-NHL, 31%) and natural killer T-cell lymphoma (NKTL, 20%). Moreover, 27% of patients had prior auto-haematopoietic stem cell transplanta-tion (auto-HSCT), and 84% received reduced intensity conditioning (RIC). Donor types were matched sibling donor (45%), matched unrelated donor (29%), haploidentical donor (19%) and cord blood (CB, 7%). RESULTS: After median follow-up of 56 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) for all patients were 38% and 45%, respectively. Non-relapse mortality (NRM) was 15% at day 100 and 24% at 1 year. On univariate analysis, complete remission status at transplant and RIC confers superior OS. On multivariate analysis, HL was associated with superior OS compared to NHL, whereas matched unrelated donor transplant was associated with significantly inferior OS compared to matched sibling donor. CONCLUSION Long-term curative durability was observed with allo-HSCT for patients with relapsed/ refractory lymphomas. This real-world data serves as a valuable historical benchmark for future studies on lymphomas in Singapore and the Asia Pacific region.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Retrospective Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods* ; Middle Aged ; Transplantation, Homologous ; Young Adult ; Transplantation Conditioning/methods* ; Lymphoma/mortality* ; Adolescent ; Hodgkin Disease/mortality* ; Aged ; Lymphoma, B-Cell/mortality*

Humans ; Pulmonary Disease, Chronic Obstructive/therapy* ; Asthma/therapy*

Humans ; Female ; Human Papillomavirus DNA Tests ; Early Detection of Cancer ; Prospective Studies ; Uterine Cervical Neoplasms/diagnosis* ; Singapore

A case study highlighting the complexity in the management of newly diagnosed atrial fibrillation in an elderly female with recurrent falls and a lack of mental capacity. This demonstrates a delicate balance between reducing thromboembolic phenomenon and bleeding risks.