GASTRIC CANCERS IN SINGAPORE: POOR PROGNOSIS ARISING FROM LATE PRESENTATION

Background : Mortality rates from gastric cancer, apart from those derived from Japanese series, remain poor. This paper sought to determine the present outcome of gastric carcinoma in a predominantly Chinese population in Singapore. Prognostic factors useful in predicting survival were also evaluated in this population. Method : All cases of histologically confirmed gastric adenocarcinoma presenting in 1992 were entered into a prospective database. Prognostic factors related to age, sex, site of disease, depth of invasion, histological grade, nodal status and stage of disease were evaluated in patients with resectable disease to determine their utility in predicting survival. Results : Of 1310 consecutive patients with histologically proven adenocarcinomas, 37% had distant metastases at presentation predominantly in the liver (21%) and peritoneal cavity (20%). Sixty-four per cent of patients underwent surgery and in only 51% of these patients was resection of the turnour possible. Stages 111 and IV (T4N2) locally advanced disease were present in 38% of patients. Thus the majority of patients presented with late or metastatic disease (75%, stages 111 and IV). Sixty per cent of patients were alive at I year and 40% at 2 years after resection of the tumour (Kaplan-Meier survival plots). In contrast, no patient survived longer than a year if the tumour was not resectable (P < 0.001, log-rank test). Median survival of patients without surgery was 12 weeks. Median survival for patients with resected stage IV disease was 23 weeks, compared to 18 weeks after surgical bypass. Age, sex, site, depth of invasion and histological grade did not significantly predict survival. Patients with node-negative disease survived longer (2 year, 70%) than those with nodal involvement (2 years, 44%; P = 0.06, log-rank test). Pathologic staging with the TNM system was useful in predicting survival (P < 0.001). Sixty per cent of patients with stage I and II disease were alive at 2 years compared to 54% with stage III disease and 0% with stage IV disease. Conclusion : The prognosis of stomach cancer remains poor, due predominantly to late presentation. Pathologic TNM staging and nodal status were useful in predicting survival outcome after resection. If the tumour were resectable, survival was appreciable even in patients with advanced stage III (2 years, 54%) and stage IV (1 year, 40%) disease. Strategies to improve outcome should focus on early detection of gastric carcinomas.     

Unknown Uterine Sears, Unknown Risks

EDITORIAL COMMENT: We accepted these case reports for publication not only to remind readers that a classical Caesarean scar is more likely than a lower uterine segment scar to rupture or dehisce, but also to stress that women should be counselled appropriately when classical Caesarean section has been performed. Our Australian population is also mobile and women may not return to the same institution or obstetrician for their next confinement. Tracing the details of a previous delivery from another hospital or practitioner even in the same community should be a routine enquiry when a patient has had a Caesarean section in a previous pregnancy but the required information is often difficult to obtain. The woman herse(fis the essential repository for this information. It should also be noted that the recent increase in the number of Caesarean sections performed for fetal indications before 30 weeks' gestation has resulted in more vertical incisions because of a poorly formed lower uterine segment.     

Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Focus groups: their role in developing calcium-related education materials

Because attitudes concerning a topic can diminish the effectiveness of educational materials, previously identified attitudes concerning calcium intake were explored through focus group interviews during the developmental stages of calcium education materials. Although four focus groups of six to seven participants were planned, each of the four groups consisted of two to six women. All focus groups followed the same format, lasting for 60–90 min; questions progressed from the general to more specific. The focus groups revealed several attitudinal barriers toward dietary behavioural change, including lack of prior interest in the topic and lack of time. Attitudes about dairy calcium included the belief that dairy foods were high in fat and should be avoided, and the belief that dairy foods would cause stomach upsets. Also, neither younger nor older women felt that osteoporosis was a problem their age group needed to address. Readability scales were not necessarily predictive of preference. This study shows that focus group interviews make a valuable contribution to planning and evaluating nutrition education materials.     

Liver carcinogenesis by methyl carbamate in F344 rats and not in B6C3F1 mice.

Short-term and long-term carcinogenicity of methyl carbamate (MCB) was evaluated in F344 rats and B6C3F1 mice. In experiments lasting 6, 12, and 18 months, MCB was given in water by gavage to groups of 10 male and 10 female rats at 0 or 400 mg/kg body weight, 5 days per week, and to similar groups of mice at 0 or 1,000 mg/kg. At 6 months, MCB induced atypical mitoses, cytologic alterations, cytomegaly, pigmentation, necrosis, and neoplastic nodules of the liver in rats. At 12 and 18 months, carcinomas of the liver were induced by MCB in 80-90% of male rats and in 60-80% of female rats. None was observed in control rats or in mice. In the 2-year studies, MCB was given to groups of 50 male and 50 female rats at 0, 100, or 200 mg/kg and to similar groups of mice at 0, 500, or 1,000 mg/kg, 5 days/week. Chronic focal inflammation, cytologic alteration, hyperplasia, and neoplastic nodules and carcinomas (200 mg/kg groups only) of the liver were induced by MCB in rats. Liver tumor incidence data for combined experiments in rats were: males--5% in controls, 0% in 100 mg/kg group, 14% in 200 mg/kg group, and 77% in 400 mg/kg group; females--5% in controls, 0% in controls, 0% in 100 mg/kg group, 12% in 200 mg/kg group, and 63% in 400 mg/kg group. MCB was not shown to be carcinogenic in mice.     

An improved method of flexible endoscopic creation of tracheoesophageal fistula for voice restoration

We present improvements of a previously reported method of tracheoesophageal puncture for voice restoration in postlaryngectomy patients. Our method utilizes a flexible endoscope to enable the tracheoesophageal puncture to be made under direct visualization using only local anesthesia and intravenous sedation. After 3 days, the created tracheoesophageal fistula tract is mature enough to allow placement of a voice prosthesis in the office. This allows the entire procedure to be performed in an outpatient setting with minimal risk. Received: 24 October 1996/Accepted: 24 January 1997     

Involvement of Cerulospinal Glutamatergic Neurotransmission in Fentanyl-induced Muscular Rigidity in the Rat

Background: Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here.

Methods: Electromyographic signals activated by bilateral microinjection of 2.5 micro gram fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg [center dot] kg sup -1 [center dot] h sup -1) was maintained until 10 min before fentanyl was administered.

Results: Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/- (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation.     

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.     

The hepatitis B immunization programme in Singapore

A voluntary immunization programme to prevent perinatal transmission of hepatitis B virus (HBV) infection in Singapore was implemented on 1 October 1985 as an integral component of the national childhood immunization programme. Up to April 1988, a total of 68,845 mothers who attended government maternal and child health clinics were screened for the disease. Of these, 2432 (3.5%) were positive for hepatitis B surface antigen (HBsAg) and 904 (1.3%) for hepatitis B e antigen (HBeAg). Virtually all the babies born to carrier mothers completed the full immunization schedule; and in addition, those of HBeAg-positive mothers were given a dose of hepatitis B immunoglobulin at birth. The hepatitis B immunization programme was extended on 1 September 1987 to cover all newborns. About 90% of the 15,943 babies delivered in government institutions from September 1987 to April 1988 were immunized at birth, with the subsequent doses being administered at maternal and child health clinics at 4-6 weeks and 5 months later. More than 85% of the children given the full course of plasma-derived and yeast-derived hepatitis B vaccine from birth continued to have protective antibody to HBV two years after immunization. The programme is being closely monitored to assess the duration of immunity and the need for booster doses, while seronegative adults are also being encouraged to be vaccinated.