Pituitary Volume and Iron Overload Evaluation by 3T MRI in Thalassemia.

OBJECTIVE: To evaluate pituitary volume and iron overload in beta thalassemia major, with the objective of assessing the reliability of this method in predicting hypogonadism. METHODS: 3T MRI was used to measure pituitary R2 and T2* in 57 beta thalassemia major patients and 30 controls. Anterior pituitary volume was evaluated by MRI planimetry. Cardiac, hepatic, and pancreatic iron overload were also assessed using MRI T2*. Mean serum ferritin was estimated by sandwich immuno-assay. Short stature was defined as height < 3 rd percentile for age, and clinical hypogonadism defined as absence of secondary sexual characteristics at ages ≥ 13 y for females and ≥ 14 y for males. RESULTS: Short stature was present in 32 patients (56.1%). Of the 47 patients in the pubertal age group, 11(23.4%) had hypogonadism. Serum ferritin correlated positively with pituitary R2 (p = 0.004) and negatively with anterior pituitary volume (p = 0.006), whereas pituitary R2 correlated negatively with cardiac T2* (p = 0.001). Patients with hypogonadism had lower pituitary R2 (p = 0.186), T2* (p = 0.048), and anterior pituitary volumes (p = 0.012) compared to those with normal sexual maturity. Regardless of stature, no significant difference was observed between pituitary R2 (p = 0.267) and T2* (p = 0.451). Mean pituitary R2 in patients (78.99 Hz) was higher than in controls (20.8 Hz) (p = 0.0001). Anterior pituitary volume was lower in patients (264.83 mm3) than in controls (380.87 mm3) (p = 0.0001). A threshold value of 22.85 Hz for pituitary R2 gave a sensitivity of 84.2% and a specificity of 73.3% in distinguishing pituitary iron content of patients from controls, with an area of 0.864 under the ROC curve. CONCLUSIONS: 3T MRI is a reliable method to detect pituitary iron overload and predict risk of hypogonadism in beta Thalassemia.

Percutaneous Radiofrequency Ablation of Appendicular Skeleton Chondroblastoma-an Experience from a Tertiary Care Cancer Center.

PURPOSE: To evaluate safety and long-term efficacy of radiofrequency (RF) ablation in treatment of chondroblastoma. MATERIALS AND METHODS: This retrospective analysis comprised 27 consecutive patients with histopathologically proven chondroblastoma treated by RF ablation. The tumors were located in the proximal humerus (n = 6), proximal tibia (n = 8), proximal femur (n = 6), distal femur (n = 5), acromion process (n = 1), and lunate (n = 1). In 19 patients (70.3%), the tumor was in the weight-bearing area of the bone. Clinical response was assessed by comparing pain scores and functional assessment by Musculoskeletal Tumor Society (MSTS) score before and after ablation. Patients were followed for a minimum of 1 year to rule out complications and recurrence. RESULTS: Technical success rate was 100%. Mean pain score before the procedure was 7.34 (range, 7-9); all patients experienced a reduction in pain, with 25 (92.6%) patients reporting complete pain relief at 6 weeks. Mean MSTS score before the procedure was 15.4, whereas mean MSTS score at 6 weeks after the procedure was 28.6, suggesting significant functional improvement (P < .0001). Two patients developed osteonecrosis and collapse of the treated bone. There were no recurrences. CONCLUSIONS: Percutaneous RF ablation is a safe and effective option for treating chondroblastoma of the appendicular skeleton.

Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer: A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT).

IMPORTANCE: There is therapeutic uncertainty regarding use of combination or single-agent chemotherapy in the treatment of patients with gallbladder cancer who experience disease progression after first-line chemotherapy. OBJECTIVE: To compare the efficacy of capecitabine plus irinotecan (CAPIRI) vs irinotecan (IRI) alone in patients with advanced gallbladder cancer (GBC) who have disease progression after gemcitabine-based first-line treatment. DESIGN, SETTING, AND PARTICIPANTS: The GB-SELECT trial was a multicenter, open-label, phase 2, randomized clinical trial of CAPIRI vs IRI alone for treatment of gallbladder cancer in patients who had disease progression after prior gemcitabine-based chemotherapy.The study was carried out in 2 tertiary care institutions in India. Patients aged between 18 and 70 years with histopathologic diagnosis of adenocarcinoma gallbladder, advanced or metastatic disease, previous treatment with gemcitabine-based chemotherapy, adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between August 2018 and January 2020. The data were analyzed for this report with cutoff on May 19, 2020. INTERVENTIONS: Patients were randomized 1:1 to receive capecitabine, 1700 mg/m2 per day, on days 1 to 14 plus intravenous irinotecan, 200 mg/m2, on day 1 or intravenous irinotecan, 240 mg/m2, on day 1, in 21-day cycles until disease progression or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS) at 6 months. The secondary end points were progression-free survival and quality of life. RESULTS: A total of 98 patients were randomized, 49 in each arm, with median (range) age of 51 (29-70) years, with 60 (61%) being women. In the CAPIRI vs IRI arms, the number of deaths at 6 months, 6-month OS, and median OS were 35, 34, 38.4% (95% CI, 24.2%-52.6%) and 5.16 (95% CI, 4.26-6.06) months vs 34, 29, 54.2% (95% CI, 39.4%-69.0%) and 6.28 (95% CI, 4.25-8.30) months, respectively, with a hazard ratio of 1.02 (95% CI, 0.64-1.49, P = .93). There were no chemotherapy-related deaths but more patients required dose modification in CAPIRI compared with the IRI arm (13 [27%] vs 4 [9%], respectively, P = .03). CONCLUSIONS AND RELEVANCE: There was no significant difference in OS between treatment with capecitabine plus irinotecan or irinotecan alone among previously treated patients with gallbladder cancer. Single-agent irinotecan should be the preferred treatment option for such patients. TRIAL REGISTRATION: CTRI/2017/10/010112.

Wrist Deformity in Children and Adolescents with b-thalassemia on Oral Iron Chelation Therapy.

OBJECTIVE: To describe a novel wrist deformity in b-thalassemia major patients, and their radiographic and magnetic resonance imaging findings. METHODS: 30 patients with b-thalassemia major who were noticed to have ulnar deviation at wrist joint were evaluated for previous history of medications, serum ferritin levels, presence of pain and swelling at the wrist joint, and the duration of iron chelation therapy. Radiographs of wrist and limited magnetic resonance imaging (MRI) sequences were obtained in 30 and 15 patients, respectively. RESULTS: Radiographs revealed varying severity of distal ulnar shortening, distal radial slanting and presence of soft tissue distal to the ulna. MRI showed similar deformities along with abnormal marrow signal at distal ulnar ends; in 8 patients, a soft tissue distal to the distal end of ulna was noted. CONCLUSIONS: Varying severity of radiological abnormalities, predominantly affecting the distal ulna, are present in children and adolescents with b-thalassemia receiving oral chelation therapy.

Intracranial Hematopoiesis in Beta Thalassemia: A Case Series.

Extramedullary hematopoiesis (EMH) is a normal response to failure of hematopoiesis at its normal site i.e., bone marrow. It is a manifestation of many congenital hemolytic anemias and marrow failure secondary to myelodysplastic syndromes. Usually, extramedullary myeloid proliferation occurs in liver, spleen and lymph nodes. However, there are many unusual sites where EMH can occur. The authors report two cases of intracranial extramedullary hematopoiesis in beta thalassemia. In one of these patients, epidural soft tissue was detected along frontal and parietal convexities causing compression of brain parenchyma leading to raised intracranial tension and sagging of brain stem, corpus callosum and herniation of cerebellar tonsils. The other case had a similar but unilateral epidural soft tissue. Expansion of diploic spaces of skull was seen in both these cases. As myeloid proliferation is slow, it presents with subtle symptoms of headache and gradually progressive lower limb weakness. A high index of clinical suspicion coupled with imaging findings is the only way to confirm the diagnosis.