Immune checkpoint inhibitors and endocrine side effects, a narrative review.

Immune checkpoint inhibitors (ICPIs) are novel drugs in the field of oncology however carry the risk of immune-related dermatologic, gastrointestinal, and endocrine side effects which can be fatal. These new innovative immunoregulatory drugs have intertwined the fields of oncology and endocrinology. CTLA-4 and PD-1 are co-inhibitory receptors on T cells that turn the T cell 'off' when binding to receptors on APCs. Tumor cells can also carry receptors for CTLA- and PD-1. By rendering T cells inactive, tumor cells can evade immune attack. Antibodies that bind to CTLA-4 and PD-1 lead to T cell activation and destruction of both tumor and normal host cells. ICPIs have been used in a variety of malignancies including melanoma, kidney cancer, and non-small cell lung cancer. A unique underrecognized side effect of the autoimmune response is hypophysitis leading to central adrenal insufficiency which can be fatal. Additional immune-related adverse events (irAEs) include hypothyroidism, hyperthyroidism, diabetes, and hypoparathyroidism.

Phaeochromocytoma of the urinary bladder.

The occurrence of urinary bladder paragangliomas is rare. A 12-year-old Chinese girl who presented with history of blurring of vision was found to have grade IV hypertensive retinopathy. Investigations revealed a phaeochromocytoma on the posterior wall of the urinary bladder. A partial cystectomy with right ureter reimplantation was undertaken and her hypertension was promptly controlled. The diagnosis and management of this rare tumour is discussed.

Ultrasound in the assessment of the palpable breast mass.

The aim of the study was: to obtain the profile of patients (with regards to age and family history of breast cancer) with a palpable breast mass. To determine the validity of ultrasound in the assessment of the palpable breast mass by determining the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound in distinguishing a malignant mass. To determine the most discriminating ultrasound characteristics for differentiating benign and malignant masses. Seventy patients who had fine needle aspiration cytology of a palpable breast mass were subjected to an ultrasound assessment of the mass. The ultrasound findings were classified as benign, indeterminate or malignant. These findings were then compared with either the cytology or histology results in cases that eventually had surgical excision. The age of the patients ranged from 15 to 66 years old The majority was in the third and fourth decades with an average age of 25 years. The 8 patients with a proven malignant breast mass were aged between 39 and 66 years old. They did not have any family history of breast cancer. Only 4 patients had a family history of breast carcinoma and all proved to have a benign breast lesion. Ultrasound had a sensitivity of 100%, specificity of 85.7%, positive predictive value of 50%, negative predictive value of 100% and accuracy of 87.5% for distinguishing a malignant mass. For benign masses: 93.7% had well-defined margins, 81.3% had homogenous internal echoes, 91.7% had depth-width ratio of less than 1.0 and 89% were compressible. For malignant masses: 87.5% had either ill-defined or irregular margins, 87.5% had inhomogenous internal echoes and mixed posterior echoes, and 100% were incompressible. The majority of patients with a palpable breast mass were aged below 40 years old. Most of the patients with a malignant breast mass were aged 40 years and older. Neither a positive nor a negative family history of breast cancer had any significance on outcome. Ultrasound had high sensitivity, specificity and accuracy in distinguishing a malignant mass. The most discriminating benign ultrasound characteristic was compressibility. The most discriminating malignant ultrasound characteristic was ill-defined and irregular margins.

Cervical sympathetic schwannoma simulating a thyroid nodule.

Schwannomas are rare tumours arising from peripheral nerve linings. A case of a schwannoma arising from cervical sympathetic chain is presented. The clinical presentation was that of a right solitary thyroid nodule. Intra-operatively, a 3 x 3 cm encapsulated lesion was seen arising posterior to the vagas nerve and attached to the cervical sympathetic trunk. The lesion was excised together with part of the nerve. Post-operatively, the patient developed Horner's syndrome that persisted. Unitil 2000, less that 50 cased of cervical sympathetic schwannoma have been described in the Englidh literature. A brief description of the pathology, presentation, diagnosis and treatment of this condition is presented.

Pancreatic insulinomas--a study of 15 cases from 1978-98.

Fifteen cases of insulinoma were managed at HUKM over a period of 20 years. Although all patients presented with neurological symptoms, the diagnosis was delayed in all. Fasting hypoglycaemia and the measurement of C-peptide levels eventually made the diagnosis. Pre-operative localization investigations were not particularly useful. Intraoperative ultrasound (IOUS) detected 72% of the insulinomas, while 93% of the insulinomas were identified intraoperatively by palpation. All the insulinomas were detected intraoperatively with the combination of the two techniques. Twelve of 15 patients had benign adenomas including one patient with MEN-1 syndrome. Two patients had malignant insulinomas. One patient refused surgery. Nine patients underwent pancreatic resections and the remaining 5 patients had the adenomas enucleated.

Typhoid thyroiditis.

Acute suppurative thyroiditis in a 62 year old lady with enteric fever is reported. Plain radiography of the neck showed a distinct localised abscess cavity with air fluid level. A rare causative agent Salmonella typhi was isolated. Needle aspiration and antibiotics resulted in complete recovery.

Managing the solitary thyroid nodule.

Solitary thyroid nodules are commonly seen in surgical outpatient clinics. A detailed history and a careful physical examination are essential. In the management of the solitary thyroid nodule, fine needle aspiration cytology has become the cornerstone investigation. Ultrasound cannot differentiate between benign and malignant nodules, however is useful in the follow-up period to identify any further nodular growth. As thyroid malignancy occurs in both hot and cold nodules, radionuclide scans are not useful in the management of solitary thyroid nodules. We have attempted to outline the process of managing the solitary thyroid nodule and discuss the options available.

The surgical treatment of adrenal diseases.

Between January 1978 to December 1993, 130 cases of adrenal diseases were diagnosed and surgically treated at the National University of Malaysia. They were 58 cases (44.6%) of Conn's syndrome, 40 cases (30.7%) of Cushing's syndrome, 20 cases (15.3%) of phaeochromocytoma and 12 cases (9.2%) of adrenocortical carcinoma (ACC). The commonest cause of Conn's syndrome was an adenoma (96.5%) which affected the left gland four times more than the right gland. Cushing's syndrome was caused by adrenocortical adenoma (32.5%), diffuse bilateral adrenal hyperplasia (40.0%), pigmented macronodular hyperplasia (20.0%) and adrenal carcinoma (7.5%). Twenty-five percent of the phaeochromocytomas were extraadrenal in origin arising mainly from the abdominal sympathetic chain. More than 50% of ACCs were non-functioning tumours. Fifty percent of the patients with ACC had inoperable tumours. The prognosis was poor even with adjuvant chemoradiotherapy. The main surgical approach was the anterior transabdominal route. There was no operative mortality or morbidity in all operated cases.

Primary hyperparathyroidism with carcinoma of the right breast--a case report.

A patient with carcinoma of the right breast and coincidental primary hyperparathyroidism is presented. The distinction between hypercalcemia of malignant and hyperparathyroid origins is based on biochemical analysis and localisation of parathyroid adenoma on a computer tomogram of the neck.

Continent pouch ileostomy.

Continent pouch ileostomy is fashioned for patients who need a proctocolectomy. It is usually indicated for cases of ulcerative colitis and familial adenomatous polyposis where the anal sphincter can no longer maintain normal function or has to be removed. A case of familial adenomatous polyposis with features of Gardner's syndrome is reported. The patient presented with carcinoma of the rectum. Abdominoperineal resection followed by completion pancolectomy was performed. A continent pouch ileostomy was fashioned for him. He resumed work as a labourer within six months. The pouch was troublefree, needed to emptied four to six times a day and was fully continent of fluid, flatus and faeces until his demise three years later from liver secondaries. Continent pouch ileostomy is a better alternative than permanent end ileostomy. All care should be taken to rule out the existence of Crohn's disease. It is proposed that continent pouch ileostomy should be offered to patients needing permanent ileostomy if the expertise is available.

Primary lymphangiomyomatosis with chylous ascites.

Primary lymphangiomyomatosis is a benign tumour of lymphatic channels and lymph nodes, clinically manifested by chylous ascites. This disease is usually progressive and unresponsive to surgery, chemotherapy or irradiation. A case of a 36-year-old lady with chylous ascites due to underlying primary lymphangiomyomatosis is reported.

Prebiopsy localization of nonpalpable breast lesions.

Radiologically guided localization procedures are indicated pre-operatively when breast lesions are nonpalpable. The results of 42 percutaneous hookwire localizations over a period of 3 years are described. Of the total, 7 (17%) were found to be malignant. Biopsy was indicated by mammographically detected mass in 48%, by microcalcifications in 40% and by microcalcifications with an associated mass in 12%.

Fine needle aspiration cytology of the breast: an analysis of 1,094 aspirates.

Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the breast in 918 cases is presented. Correlation between the FNA cytology and subsequent histology of the lesions was available in 211 cases. FNA had a sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall diagnostic accuracy rate was 95.7%.

Treatment of bleeding gastroesophageal varices: a report of forty-four cases.

Bleeding gastroesophageal varices is associated with a high morbidity and mortality. Forty-four cases of bleeding gastroesophageal varices were treated at the Department of Surgery, Universiti Kebangsaan Malaysia, General Hospital, Kuala Lumpur over four and a half years. Thirty-two of them had liver cirrhosis. Hepatitis B infection was noted in 13 and alcoholic abuse was present in 14 patients. Five patients had associated hepatoma. Thirty-four percent had gastric fundal varices and a third of these bled from them. A total of 179 endoscopic injection sclerotherapy sessions were performed averaging 4 per person. Rebleeding rate was 4% and mortality was high (50%) in these cases. It was concluded that injection sclerotherapy is a safe and effective means of controlling bleeding oesophageal varices. Operative surgery was employed in those who rebled after injection and would be considered in those in Child's A.

Primary hyperparathyroidism--a surgical review of 12 cases.

Twelve cases of primary hyperparathyroidism operated by the Universiti Kebangsaan Malaysia Surgical Team from 1978 to 1989 were reviewed. There was a preponderance of Indian females in this series. The majority of the cases presented late and with complications. Renal calculi and bone disease were the commonest complications noted. Of the 12 patients, 9 had single parathyroid adenoma of which 4 were ectopically located, and 2 had hyperplasia of the parathyroids. These were all successfully operated. The remaining patient had 2 failed neck explorations. Failure at initial exploration was due to ectopic location of the glands. Meticulous surgical technique, knowledge of the anatomical variations of location of the parathyroid glands and availability of frozen section facility are essential for successful outcome.

Adrenal histoplasmosis in Cushing's syndrome with bilateral adrenocortical nodular hyperplasia.

Adrenal histoplasmosis in Cushing's syndrome of adrenal origin is rare. A patient with Cushing's disease with bilateral nodular hyperplasia and histoplasmosis of both the adrenal glands is described. The diagnosis of histoplasmosis was only made post operatively as the constitutional manifestations, besides being partially masked by hypercortisolism also resemble those of tuberculosis.

Portal hypertension due to arteriovenous fistula of the gastroduodenal artery.

The record is presented of a patient with severe recurrent bleeding due to portal hypertension. Surgical control of the feeding vessels of a fistulous communication between the gastroduodenal artery and its companion vein arrested the haemorrhage and controlled the portal hypertension.

Isolated perforations of the ileum and jejunum in blunt abdominal trauma.

A report of ten cases of perforations of the ileum and jejunum from blunt abdominal trauma is presented. The perforation was the only injury in eight patients, while in two there were other visceral injuries. The perforations were single in seven patients and double in three. Simple closure was used in seven cases and resection in three. Of the three patients who were operated upon late, one died.