Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

Demographics and outcome of patients with congenital haemophilia in Sarawak, Malaysia.

INTRODUCTION: Sarawak has a population that is geographically and characteristically widely varied. This study aimed to determine the demographic profile of patients in Sarawak, Malaysia. Materials and Methods - A cross-sectional study was conducted in 2019 at four major haemophilia treatment centres in Kuching, Sibu, Bintulu and Miri Hospitals, Sarawak. Demographic and clinical data were collected with consents from patients. RESULTS AND DISCUSSION: Ninety-six haemophilia patients were identified - 79(82.3%) haemophilia A(HA) and 17(17.7%) haemophilia B(HB). Severe haemophilia patients were noted in 45.6% (36/79) of HA and 64.7% (11/17) of HB. In all 44.3% of the HA and 52.9% of the HB population had no identifiable family history of haemophilia. Two-thirds of the patients with severe HA were on prophylaxis [24/36 (66.7%)] and only onethird [4/11 (36.4%)] in severe HB. Inhibitors developed in 9/79 (11.4%) of the HA population [3/79 (3.8%) high responders]. The median inhibitor titre was not significantly different between the different treatment groups - on demand versus prophylaxis (1.0BU versus 2.0BU; z statistic -1.043, p-value 0.297, Mann-Whitney test). None of the patients developed inhibitory alloantibodies to factor IX. Four HA patients (5.1%) underwent immune tolerance induction where one case had a successful outcome. Three severe HA patients received emicizumab prophylaxis and showed remarkable reduction in bleeding events with no thromboembolic events being reported. One female moderate HA patient received PEGylated recombinant anti-haemophilic factor. Eleven patients underwent radiosynovectomy. One mild HB patient succumbed to traumatic intracranial bleeding. Our data reported a prevalence (per 100,000 males) of 5.40 cases for all severities of HA, 2.46 cases for severe HA; 1.16 cases for all severities of HB, and 0.75 cases for severe HB. The overall incidence of HA and HB was 1 in 11,500 and 1 in 46,000, respectively. CONCLUSION: This study outlines the Sarawakian haemophilia landscape and offers objective standards for forward planning. Shared responsibilities among all parties are of utmost importance to improve the care of our haemophilia population.

Clinical spectrum of children receiving palliative care in Malaysian Hospitals.

INTRODUCTION: Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services. METHODS: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out. RESULTS: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients. CONCLUSION: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.

Frequent occurrence of gastric cancer in Asian kindreds with Li-Fraumeni syndrome.

Type of cancer and age of onset in individuals with inherited aberrations in the tumour suppressor gene TP53 are variable, possibly influenced by genetic modifiers and different environmental exposure. Since 2009, the modified Chompret criteria (MCC) have been used to identify individuals for TP53 mutation screening. Using the TP53 mutation database maintained by the International Agency for Research on Cancer (IARC), we investigated if the MCC, mainly developed for a Caucasian population, was also applicable in Asia. We identified several differences in Asian families compared with similar Caucasian cohorts, suggesting that identification and management of Li-Fraumeni syndrome in Asia do not completely mirror that of North America and Western Europe. Early gastric cancer (<40 years) may be considered a new addition to the MCC especially for Asian families.

Mild autosomal recessive osteopetrosis: successful treatment with bone marrow transplant.

We describe a 5 1/2 year old boy who was diagnosed with mild autosomal recessive osteopetrosis based on the presence of bony sclerosis, extramedullary haematopoeisis, leukoerythroblastosis and visual impairment who had an allogeneic bone marrow transplant from a matched sibling donor. Conditioning regime was busulphan 16 mg/kg and cyclophosphamide 200 mg/kg. Apart from transient hypercalcaemia, there were no major post transplant complications. Four years post transplant, the extramedullary haematopoeisis has resolved completely with normal blood counts. Apart from a fracture after a trivial fall two months after transplant, he has not suffered any fracture related limb deformities.

Early presentation of right adrenal mass, hepatoblastoma and hepatic cavernous haemangioma in Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann Syndrome (BWS) is associated with early development of embryonal tumours usually in the first four years of life. We describe a patient who presented with a right adrenal cyst in the first month of life and hepatoblastoma in the third month of life. A cavernous haemangioma was subsequently found in the resected tumour.

Chromosome 13q deletion with Cornelia de Lange syndrome phenotype.

A 3-year-old girl with facial dysmorphic features suggestive of Cornelia de Lange syndrome was seen in the ophthalmology unit for a right leukocoria. The leukocoria was found to be caused by a large retinoblastoma and the right eye was enucleated. Chromosomal analysis revealed partial chromosome 13q deletion involving band 14 which is associated with a high risk of retinoblastoma. This case shows that patient with chromosome 13q deletion syndrome cannot be diagnosed based on dysmorphic features only. Chromosomal analysis is warranted in all infants with facial dysmorphism suggestive of Cornelia de Lange syndrome so that those with chromosome 13q deletion can be referred early for early detection of retinoblastoma.

Moulded cement-prosthesis for osteosarcoma of the proximal humerus.

We report a case of an 11-year-old boy with osteosarcoma of the proximal humerus treated with wide excision and reconstruction with a cement spacer-prosthesis. After seven years of follow-up, the patient is now almost a young adult. We present his current physical and functional status, which seems to defray the initial doubts regarding long-term problems when we chose this method of reconstruction.

Coexistent bronchogenic carcinoma and active pulmonary tuberculosis.

Sixty-four cases of coexistent bronchogenic carcinoma and active pulmonary tuberculosis were diagnosed between 1969 and 1976. The majority were male chronic cigarette smokers in their fifth and sixth decades. Human bacilli were isolated in 48 patients (88.9 percent) and atypical bacilli in six patients (11.1 percent). All of the atypical bacilli and 8.3 percent of the human bacilli were found to be resistant to the first line antituberculous drugs. All patients, except two who died following resection, were given a course of antituberculous drugs with 93.8 percent successful sputum conversion. Uncontrolled or disseminated tuberculous infection was not observed. Forty-five patients (70.3 percent) underwent pulmonary resection. Median survival time of those who had curative resection was 14.3 months with a 5 year survival rate of 13.2 percent. Median survival times of those treated by palliative resection plus anticancer chemotherapy and by anticancer chemotherapy alone were 8.3 months and 11.1 months, respectively. None of these patients survived more than 30 months. It appears that, clinically, each disease runs its own course with little effect on the other.

Factors influencing morbidity and mortality in esophageal carcinoma.

In 1977, 152 patients with carcinoma of the esophagus were admitted under our care. The lesions were located from the hypopharynx to the cardiac portion of the stomach. A prospective study was conducted and the results (mortality and morbidity) were analyzed by computer. Resection was possible in 88 patients and a bypass procedure in 15. On exploration in five patients, the disease was found to be so extensive that no further operative procedures were undertaken. The mortality rate was high, hospital deaths being included in the operative mortality statistics. The best results were obtained by applying the Lewis-Tanner one-stage esophagectomy. When the disease was extensive, a bypass procedure using the Kirschner operation and postoperative irradiation was the method of choice. When the general condition of the patient was poor, the best procedure was a staged esophagectomy, with the reconstruction being undertaken at a later date.

Observations of pressure waves in stomach, jejunal, and colonic loops used to replace the esophagus.

The motility characteristics of the stomach, upper jejunum, and right colon were studied in 25 patients in whom these organs were used to replace the resected esophagus. The pattern of motility in all three replacement organs generally was similar to that recorded in normal individuals by other workers. But the stomach replacement showed a greater percentage of Type 1 waves, and Type II contractions were weaker. Activity in the jejunal replacements was much reduced. A propagated pressure wave was observed on swallowing water in the jejunal replacements. The nature of this wave needs further elucidation. The functional result was good, except in patients with a weak or without an upper esophageal sphincter. Patients experienced no pain during the test and no side effects were observed.

Fine-needle aspiration versus drill-needle biopsy of thyroid nodules: a controlled clinical trial.

Percutaneous needle biopsy by two different methods was evaluated in a prospective controlled study of 167 consecutive patients with dominant thyroid nodules. Fine-needle aspiration was superior to high-speed drill-needle biopsy because of its higher diagnostic yield (93.9%). When a sample sufficient for diagnosis was obtained, the accuracy rate for both methods was comparable. Diagnostic errors were due to inadequate samples, difficulties in interpreting hypercellular adenomas, and geographic sampling problems. In the detection of thyroid cancer, neither technique alone appears completely adequate because of occasional false negative errors. The selection of patients for operation should depend on clinical parameters as well as the findings on fine-needle aspiration of thyroid nodules.

Gastric histology and function in patients with intrathoracic stomach replacement after esophagectomy.

The histological changes and gastric function alterations in 19 patients who had intrathoracic stomach replacement following esophagectomy were studied. Atrophic gastritis was noted in 13 of the 19 patients. The mechanical response of the stomach to distention by food was largely retained. The basal and maximal acid output was reduced markedly, and the serum gastrin was elevated. An association between the degree of gastritis, the percentage of gastric motility at rest, and acid secretion is demonstrated. These changes are consistent with patients with duodenal ulcer following vagotomy and dyloroplasty. Postprandial elevation in serum gastrin was noted in patients with or without vagotomy. The lack of significant difference in integrated gastrin response suggests that the vagus may not be important in the control of postprandial gastrin release.

Late result of sphincteroplasty in the treatment of primary cholangitis.

Sphincteroplasty is one of the surgical procedures used in the treatment of primary cholangitis. We performed this operation on 342 patients over a 13-year period, with an operative mortality of 4.7%. Postoperative examination of 271 patients (average follow-up, seven years four months) showed that a good result was achieved in 226 patients, a fair result in 23 patients, and a poor result in 22 patients. Analysis of the reoperations in 17 patients showed that stone reformation is the most common finding, followed by sphincteroplasty stricture, liver abscess, and empyema of the gallbladder. When performed with proper indications in the management of primary cholangitis, sphincteroplasty is a safe procedure, and the majority of patients can expect good results.

Epidural hygroma of the posterior fossa. Case report.

A case of posttraumatic epidural hygroma is reported. This child presented with occipital injury. Slowly but progressively he developed bilateral Wallenberg's syndrome and retrocollis. Correct preoperative diagnosis was made with the aid of computerized tomography. The case is discussed with emphasis on the mechanism of formation of an epidural hygroma and its clinical presentation.

Bacteria and septic complications in patients with perforated duodenal ulcers.

To evaluate the clinical significance of bacterial contamination in perforated duodenal ulcers, we prospectively studied septic complications in 184 consecutive patients. All patients received parenteral antibiotics (over 90 percent preoperatively) for at least 7 days. Thirteen infections developed in eight patients (4.3 percent). Peritoneal cultures, performed in 143 unselected patients, were positive in 33.6 percent of cases. Bacterial growth occurred more often and in heavier amounts in patients who underwent exploration late (after 48 hours) and those who had gross peritoneal soilage. Candida and gram-negative organisms predominated, but there was no correlation with pathogens that produced abscesses or wound infections. Old age and late exploration significantly increased the risk of infection. Neither peritoneal soiling nor a positive culture was likely to be clinically important when explorations was performed within 2 days of perforation. We treated perforated ulcers as clean-contaminated cases, and recommend that three doses of prophylactic antibiotics be begun preoperatively in all patients.

Survival after surgery for advanced carcinoma of the stomach other than the cardia.

The survival of 103 patients operated on for advanced carcinoma of the stomach other than the cardia was assessed. The median duration of survival for patients subjected to palliative partial gastrectomy, total gastrectomy, gastrojejunostomy, and biopsy only was 24, 22, 11, and 10 weeks, respectively. All of these patients had definite residual tumor. In the 27 patients with preoperative signs of incurable tumor, the high operative mortality rate (19 percent), the low rate of resectability (26 percent), and the short duration of survival in the patients who had resection (median 11 weeks) combined lead to the conclusion that exploration for the possibility of resection is not worthwhile.

Techniques and therapies for primary and metastatic liver cancer.

In summary, of the 460 patients of primary carcinoma of the liver admitted to the University Surgical Unit at the Queen Mary Hospital over a period of 12 years, more than 40% could not be treated, and only 91 of the patients were candidates for curative resection. The cure rate is very small; a 1- to 2-year survival was obtained in 46% of 15 resections. From 1964 to 1969, out of 22 patients with resections, 3 are still alive more than 5 year after the operation. Lin30 reported a 19.1% 5-year survival. When the hepatoma has ruptured and bleeding takes place, surgical treatment is obligatory to control the hemorrhage. Ninety-eight patients underwent a clinical trial of 5 categories: hepatic dearterialization, hepatic arterial cannulation and infusion of 5-FU, hepatic arterial ligation and portal venous infusion of 5-FU, radiotherapy and no treatment. The results show that the advantage of each form of treatment when compared with no treatment is marginal. Thus a gloomy picture of primary hepatoma is held. Since the operative mortality of hepatic resection for a solitary secondary carcinoma of the liver is negligible, it should be done in each instance because a long-term survival may be possible. This is especially true with primary carcinoma of the colon.

Tracheostome construction during laryngectomy--a method to prevent stenosis.

A new technique for construction of the tracheostome at the time of total laryngectomy is described. It involves making an X-shaped incision on the lower skin flap and four slits on the divided trachea. The result is a serrated suture line at the tracheocutaneous junction. The incidence of stenosis in 116 patients who did not have this method of construction was 31%. Sex difference and previous irradiation was not found to be related to the occurrence of stenosis. Of 25 patients who had the new method of tracheostome construction, only one patient had to wear a tube until she died at 7 months. The rest, followed up for at least 9 months, did not have stenosis. It is concluded that this new method of tracheostome construction will reduce the incidence of stenosis.

Intracranial arteriovenous malformations in the Chinese.

A series of 32 intracranial arteriovenous malformations in the Chinese is retrospectively studied. Their salient clinical, radiological and morphological features are presented together with their eventual outcome. Contrasting features from reported western series are compared.