Favorable outcome of a histiocytic sarcoma patient treated with immune checkpoint inhibitor: a case report.

Introduction and Importance: Histiocytic sarcoma (HS) is an extremely rare malignancy in which there has been no standard treatment approach. Some preclinical studies have provided rationales for the application of immunotherapy in advanced HS. Case Presentation: The authors reported a case of a 61-year-old patient with metastatic HS who had a rapid progression on ifosfamide, carboplatin, and etoposide chemotherapy. The authors performed PD-L1 testing, which showed a strong positivity in 90% of tumor cells. The patient was then treated with pembrolizumab 200 mg every 3 weeks. He refused palliative radiotherapy. A dramatic response in all sites was recorded on the PET-CT scan after three cycles. He was maintained on pembrolizumab, reaching over 30 months without disease progression. Clinical Discussion: Recent molecular data suggests there could be a role of immunotherapy in HS. In our patient, the disease was refractory to chemotherapy and pembrolizumab has been given based on the strong PD-L1 expression. Response to immunotherapy has also been recorded in several cases with malignant histiocytic neoplasm. Conclusion: Immunotherapy might bring sustained disease remission in PD-L1 high expression HS and further studies evaluating the role of immune checkpoint inhibitor in this disease are warranted.

Ovary metastasis from lung cancer mimicking primary ovarian cancer: A rare case report.

Introduction: Ovarian metastasis from lung cancer is very rare, which might lead to a misdiagnosis as primary ovarian cancer. Case presentation: We report a 49-year-old woman presenting to our hospital because of a painful mass in the lower abdomen, with no respiratory symptoms. Her initial diagnosis was stage IVB ovarian cancer with pulmonary metastasis. Therefore, the patient underwent neo-adjuvant Paclitaxel - Carbolatin chemotherapy followed by interval debulking surgery. However, postoperative histopathology and immunohistochemistry findings confirmed the diagnosis of primary lung cancer with ovarian metastases. EGFR exon 19 deletion mutation was found by tumor analysis. Therefore, she was then treated with erlotinib and the disease achieved the partial response and remained stable for 7 months. Conclusion: Diagnosis of lung cancer in the context of ovarian and peritoneal metastases can be difficult. In this circumstance, thorough systemic assessment and immunohistochemistry are essential to confirm the primary.

Recurrent ovarian cancer presenting with isolated axillary lymph node metastasis: A rare case report.

Introduction: Ovarian cancer with metastatic axillary lymph node is a very rare entity. This study aims to report a case of recurrent ovarian cancer presenting with isolated axillary lymph node metastasis. Case presentation: We report a case of a 58-year-old patient with recurrent ovarian cancer in the axillary node and a suspected lesion in the ipsilateral breast. One year before recurrence, the patient was diagnosed with FIGO stage IIIC ovarian cancer and was treated with primary debulking and paclitaxel-carboplatin adjuvant chemotherapy. Biopsies of the breast lesion, right and left axillary lymph node yielded a fibroadenoma in the breast and a metastatic carcinoma in the axillary node. Immunohistochemistry stains of the left axillary node biopsy specimen was positive for CK7, P53 and PAX-8 markers, and negative for CK20 and GCDFP-15 markers. Immunohistochemistry results combined with a history of ovarian cancer helped confirm the ovarian origin of axillary lymph node metastasis. Clinical discussion: Recurrent ovarian cancer presenting with isolated axillary lymph node metastasis is rare. Immunohistochemistry combined with medical history is essential for definitive diagnosis in this situation. PAX-8 and GCDFP-15 help to differentiate the origin from the breast or the ovary. Conclusion: Oncologists and pathologists should recognize this rare clinical scenario for early diagnosis and treatment. Detailed medical history, imaging, and immunohistochemical studies on biopsy specimen should help reach accurate diagnosis.

Effectiveness and Tolerability of First-Line Afatinib for Advanced EGFR-Mutant Non-Small Cell Lung Cancer in Vietnam.

BACKGROUND: We aimed to evaluate the effectiveness and tolerability of Afatinib as first-line treatment of advanced epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This is a retrospective study of Vietnamese patients  with advanced EGFR-mutant NSCLC treated with first-line afatinib at the National Cancer Hospital from 1st January 2018 to 31st October 2020. Patients' demographic, clinical and treatment data were captured. Objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF) and tolerability were evaluated. We used Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. RESULTS: A total of 44 patients were included. Common EGFR mutations (Del 19/L858R) were detected in 61% patients. Fifty percent of patients with uncommon mutations had compound mutations of G719X, L861Q and S768I. The ORR was 75% while DCR rate was 98%. The median TTF was 12.3 months (95% CI: 7.2-17.3); the mTTFs were 12.3 and 10.8 months for patients with common and uncommon mutations (p = 0.001), respectively, and 14.0 and 7.5 months for patients with Del 19 and L858R mutations (p = 0.067), respectively. Afatinib 30 mg once daily was the most common starting (77%) and maintenance (64%) doses. The mTTFs were 12.3 and 7.5 months for patients with 30 mg starting dose vs 40 mg dose (p = 0.256), respectively. Diarrhea, skin rash, paronychia and fatigue were observed in 32%, 30%, 25% and 9%, respectively. There was no grade 4 toxicity except three patients with grade 3 paronychia. CONCLUSIONS: First-line afatinib is beneficial for Vietnamese patients with advanced EGFR-mutant NSCLC with a good response rate and prolonged TTF with manageable adverse event profile. Baseline brain metastasis status and starting doses do not significantly impact TTF.
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Treatment Outcome and Prognosis Factors of FIGO 2018 Stage III Cervical Cancer Patients Treated with Definitive Concurrent Chemoradiation in Vietnam.

OBJECTIVE: This study aimed to analyze the treatment outcome and toxicities, along with prognosis factors of patients with FIGO 2018 stage III cervical cancer treated with definitive concurrent chemoradiation. METHODS: A total of 83 stage III cervical cancer patients with good performance status (ECOG PS 0, 1) were treated with three-dimensional conformal radiation therapy (3D-CRT) combined with chemotherapy (weekly cisplatin), followed by high-dose-rate (HDR) brachytherapy between January 2017 and March 2019 at Vietnam National Cancer hospital. Treatment outcomes and prognosis factors were assessed along with acute and late toxicities. RESULTS: The 3-year DFS was 67.8% and 3-year OS was 80.3%. On multivariate analyses, short axis of pelvic lymph node diameter of ≥ 15mm, invasion of the lower third of vagina and para-aortic lymph node metastasis were identified as adverse prognostic factors for DFS. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥ grade 2) at the 3-year follow-up were 29.6% and 11.6%, respectively. CONCLUSIONS: 3D CRT and HDR brachytherapy with concurrent chemotherapy is an effective treatment, with acceptable toxicity for FIGO 2018 stage III cervical cancer in Vietnam.
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Comparison of Transoral Thyroidectomy Vestibular Approach and Unilateral Axillobreast Approach for Endoscopic Thyroidectomy: A Prospective Cohort Study.

Background: Various approaches for endoscopic thyroidectomy have been developed recently that improve the cosmetic outcome, and some are even scar free. In this study, we compared the safety and surgical outcomes of transoral endoscopic thyroidectomy vestibular approach (TOETVA) and unilateral axillobreast approach (UABA) thyroid surgery performed by a single surgeon. Materials and Methods: We conducted a prospective cohort study among 101 patients undergoing endoscopic thyroidectomy from 2018 to 2019 in our institution. The factors analyzed included patients' clinical characteristics, types and time of operation, blood loss, hospital stay, postoperative complications, and cosmetic satisfaction. Results: Among 101 patients, 51 underwent TOETVA and 50 had UABA surgery. UABA has shorter operative time for lobectomy (91.7 ± 16.5 minutes versus 50.4 ± 6.8 minutes, P < .001), whereas TOETVA is associated with less postoperative pain (visual analogue scale score day 1 of 4.6 ± 1.0 versus 5.8 ± 1.0, P < .001). There were no significant differences between TOETVA and UABA groups regarding rates of transient recurrent laryngeal nerve injury (9.8% versus 2.0%, P = .205) and hypothyroidism (11.5% versus 2.0%, P = .112), in which all patients fully recovered 6 months after surgery and most of them were satisfied with the cosmetic result. Conclusions: Both TOETVA and UABA have been shown to be effective and safe surgical options for endoscopic thyroid surgery, as well as gave excellent cosmetic result. Each approach has its own advantages and disadvantages, and choice of technique should be tailored for each individual, and patient preference should be integrated in the treatment plan.

Transoral Endoscopic Thyroidectomy by Vestibular Approach with Central Lymph Node Dissection for Thyroid Microcarcinoma.

Background: The transoral endoscopic thyroidectomy by vestibular approach (TOETVA) has been developed for thyroid microcarcinoma (TMC) treatment worldwide, with low rate of complications and excellent oncological results. However, this approach has still not been routinely performed. Thus, in this study, we aim to demonstrate the feasibility and safety of this technique in the clinical practice. Methods: In this prospective cohort study, 29 patients diagnosed TMC and clinically node negative underwent thyroidectomy and prophylactic central lymph node dissection by TOETVA. The clinicopathologic characteristics, surgical outcomes, and cosmetic results were evaluated. Results: The mean age was 34.7 ± 8.5 years. Three patients had underlying Grave's disease. Thyroid lobectomy with isthmusectomy was performed in the majority of cases (72.4%). All patients underwent prophylactic central node dissection. The mean number of retrieved central node was 7.8 ± 3.7 (3-19). Seven patients (24.1%) had lymph node metastasis in postoperative pathology. Among them, the mean number of metastatic lymph nodes was 2.1 ± 1.7 (1-5). The mean operative time was 121.2 ± 22.6 minutes. Four patients experienced transient hoarse and 1 patient had hematoma. Visual analog scale score on first postoperative day was 2.8 ± 1.4 (0-5). Most of patients were satisfied with cosmetic outcome. Conclusions: The TOETVA is new technique for TMC in Vietnam. The initial results of oncology, postoperative complications, and cosmetic supported the application of TOETVA in TMC.

Aggressive lactating adenoma mimicking breast carcinoma: A case report.

INTRODUCTION: Lactating adenoma is a rare breast tumor which is commonly found in late pregnancy or lactation period. Despite its benign nature, lactating adenoma might develop aggressively and can be misdiagnosed as breast cancer. CASE PRESENTATION: We report a case of a 25-year-old female presenting with two large, ulcerative and bleeding breast masses. An open biopsy demonstrating lactating adenoma was considered discordant and surgery was performed to confirm the diagnosis. CONCLUSION: Careful clinical and histological evaluations are necessary to diagnose and manage lactating adenoma.

Solitary fibrous tumor behind the pubic bone: A rare case report.

Solitary fibrous tumors (SFT) is a rare type of soft tissue tumors and there have been only a few reported cases of SFTs at the perineum region. We report a SFT below the pubic bone in a 35-year-old male causing compression on his corpus spongiosum. The patient underwent en bloc tumor resection with preservation of spermatic vessels and the bladder neck. Pathological evaluation and immunohistochemistry (IHC) staining with CD34(+), CD99(+), STAT6(+), S100(-) and Desmin(-) confirmed the diagnosis of SFT. Surgery plays a key role in treatment strategies and pathological examination with IHC is important in the diagnosis of SFTs.

A Case of Advanced Gastric Cancer with Folfiri as a Preoperative Chemotherapy.

INTRODUCTION: In advanced gastric cancer, preoperative chemotherapy is associated with survival benefit. FOLFIRI has demonstrated promising results in terms of survival and tolerance, especially in patients with poor performance status. CASE PRESENTATION: A 59-year-old male, diagnosed with pT4bN2M0 gastric cancer, underwent gastrointestinal anastomosis and three cycles of EOX chemotherapy. Due to disease progression, he was switched to FOLFIRI regimen. After 12 cycles, the patient received a subtotal gastrectomy and D2 lymphadenectomy. Microscopic examination achieved pCR, and the patient has been surviving 34 months without recurrence. No severe toxicities of chemotherapy were recorded. CONCLUSIONS: FOLFIRI might be a safe and effective option in neoadjuvant treatment for advanced gastric cancer among patients with poor performance status or progression after first-line chemotherapy.

Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam.

BACKGROUND: In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. METHODS: The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). RESULTS: Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. CONCLUSIONS: The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical.

Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies.

OBJECTIVES: The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. METHODS: Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. RESULTS: Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. CONCLUSIONS: Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds.

Estimating the Cost-Effectiveness of HIV Prevention Programmes in Vietnam, 2006-2010: A Modelling Study.

INTRODUCTION: Vietnam has been largely reliant on international support in its HIV response. Over 2006-2010, a total of US$480 million was invested in its HIV programmes, more than 70% of which came from international sources. This study investigates the potential epidemiological impacts of these programmes and their cost-effectiveness. METHODS: We conducted a data synthesis of HIV programming, spending, epidemiological, and clinical outcomes. Counterfactual scenarios were defined based on assumed programme coverage and behaviours had the programmes not been implemented. An epidemiological model, calibrated to reflect the actual epidemiological trends, was used to estimate plausible ranges of programme impacts. The model was then used to estimate the costs per averted infection, death, and disability adjusted life-year (DALY). RESULTS: Based on observed prevalence reductions amongst most population groups, and plausible counterfactuals, modelling suggested that antiretroviral therapy (ART) and prevention programmes over 2006-2010 have averted an estimated 50,600 [95% uncertainty bound: 36,300-68,900] new infections and 42,600 [36,100-54,100] deaths, resulting in 401,600 [312,200-496,300] fewer DALYs across all population groups. HIV programmes in Vietnam have cost an estimated US$1,972 [1,447-2,747], US$2,344 [1,843-2,765], and US$248 [201-319] for each averted infection, death, and DALY, respectively. CONCLUSIONS: Our evaluation suggests that HIV programmes in Vietnam have most likely had benefits that are cost-effective. ART and direct HIV prevention were the most cost-effective interventions in reducing HIV disease burden.

Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis.

INTRODUCTION: The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery. METHODS: We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery. RESULTS: Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 m(2). Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P = 0.002). We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI. CONCLUSIONS: Albumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity score methodology. Future studies should address the safety of albumin-containing fluids on kidney function in patients undergoing cardiac surgery.

Costing analysis of national HIV treatment and care program in Vietnam.

BACKGROUND: Vietnam achieved rapid scale-up of antiretroviral therapy (ART), although external funds are declining sharply. To achieve and sustain universal access to HIV services, evidence-based planning is essential. To date, there had been limited HIV treatment and care cost data available in Vietnam. METHODS: Cost data of outpatient and inpatient HIV care were extracted at 21 sentinel facilities (17 adult and 4 pediatric) that epitomize the national program. Step-down costing for administration costs and bottom-up resource costing for drugs, diagnostics, and labor were used. Records of 1401 adults and 527 pediatric patients were reviewed. RESULTS: Median outpatient care costs per patient-year for pre-ART, first year ART, later year ART, and second-line ART were US $100, US $316, US $303, and US $1557 for adults; and US $171, US $387, US $320, and US $1069 for children, respectively. Median inpatient care cost per episode was US $162 for adults and US $142 for children. Non-antiretroviral (ARV) costs in adults at stand-alone facilities were 44% (first year ART) and 24% (later year ART) higher than those at integrated facilities. Adults who started ART with CD4 count ≤100 cells per cubic millimeter had 47% higher non-ARV costs in the first year ART than those with CD4 count >100 cells per cubic millimeter. Adult ARV drug costs at government sites were from 66% to 85% higher than those at donor-supported sites in the first year ART. CONCLUSIONS: The study found that HIV treatment and care costs in Vietnam are economical, yet there is potential to further promote efficiency through strengthening competitive procurement, integrating HIV services, and promoting earlier ART initiation.

Impact of methadone maintenance on health utility, health care utilization and expenditure in drug users with HIV/AIDS.

BACKGROUND: This study assessed the impact of methadone maintenance treatment (MMT) on health utility, health care service utilization, and out-of-pocket (OOP) health expenditure in drug users with HIV/AIDS in Vietnam. METHODS: Using the 2012 Vietnam HIV Service Users Survey data, a post-evaluation was designed to compare 121 MMT patients with 347 non-MMT patients who were matched using propensity scores of MMT covariates. Health utility was measured using the EuroQOL - five dimensions - five levels (EQ-5D-5L) and a visual analogue scale (EQ-VAS). RESULTS: The mean EQ-5D-5L single index and EQ-VAS score of MMT patients were 0.68 (95% CI=0.64-0.73) and 71.5% (95% CI=68.2-74.9). Compared with the control group, the adjusted differences in health utility were 0.08 and 4.43% (p=0.07), equivalent to 12.1% and 6.5% increases during MMT. There was a 45.9% decrease in the frequency of health care service utilization that was attributable to MMT. Although, antiretroviral treatment and MMT services were free-of-charge, MMT and non-MMT patients still paid their OOP for health care for averagely US$ 16.3/month and US$ 28.9/month. The adjusted difference between the two groups was US$ 19.3/month ($ 231.6/year) that equivalents to a reduction of 66.7% in OOP health expenditure related to MMT. CONCLUSION: MMT was associated with a clinically important difference in health utility, large reductions in health care service utilization and OOP health expenditure in HIV-positive drug users. Scaling up MMT in large drug-using population could help improve the outcomes of HIV/AIDS interventions and reduce economic vulnerability of affected households.

Multilevel predictors of concurrent opioid use during methadone maintenance treatment among drug users with HIV/AIDS.

BACKGROUND: Ongoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy. METHODS: We analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations. RESULTS: Over 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR = 0.97 for 1 year increase), had economic dependents (AOR = 0.33), or were referred to TB treatment (AOR = 0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment. CONCLUSION: These findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and implementation.

Myosin heavy chain isoform expression and Ca2 +-stimulated ATPase activity in single fibres of toad rectus abdominis muscle.

Segments of single fibres from the rectus abdominis (RA) muscles of adult and juvenile cane toads (Bufo marinus) were examined for myosin heavy chain (mHC) isoform expression and Ca2+-stimulated MgATPase activity. mHC isoform analyses were carried out using the recently developed alanine-SDS-PAGE method, which separates one tonic (BmHCT) and three twitch (BmHC1, BmHC2, BmHC3) mHC isoforms in toad skeletal muscle. Ca2+-stimulated MgATPase activity was measured by spectrophotometric determination of Pi, under conditions in which the ATPase associated with the sarcoplasmic reticulum (SR ATPase) was suppressed by feedback inhibition. The mHC-based fibre types identified in this study include three pure twitch fibre types (t1, t2 and t3), expressing BmHC1, BmHC2 or BmHC3 respectively, and seven hybrid fibre types co-expressing a combination of two or three twitch and tonic or twitch and twitch mHC isoforms. The fibre populations dissected from juvenile and adult toad muscles contained 49.4% (juvenile) and 73.7% (adult) mHC hybrids. The average values for Ca2+-stimulated MgATPase in pure twitch fibres and in fibres expressing predominantly (> or = 95%) the tonic mHC isoform (Tp fibres) differed significantly (P < 0.05) from each other and decreased in the order t1 > t2 > t3 > Tp. We conclude that (i) in RA muscles of both juvenile and adult cane toads there is a large proportion of mHC hybrids, some of which co-express twitch and tonic mHC isoforms and (ii) ATPase activities associated with the four mHC isoforms expressed in toad skeletal muscles decrease in the order BmHC1 > BmHC2 > BmHC3 > BmHCT.