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Cerebral ischemia or stroke, an acute neurological injury lacking an effective therapy, is the second leading cause of death globally. The unmet need in stroke research is to identify viable targets and to understand their interplay during the temporal evolution of ischemia/reperfusion (I/R) injury. Here we report a temporal signature of the ischemic hemisphere revealed by the isobaric tag for relative and absolute quantification (iTRAQ)-based 2D-LC-MS/MS strategy in an in vivo middle cerebral artery occlusion (MCAO) model of focal cerebral I/R injury. To recapitulate clinical stroke, two hours of MCAO was followed by 0, 4, and 24 h of reperfusion to capture ischemia with an acute and subacute durations of reperfusion injury. The subsequent iTRAQ experiment identified 2242 proteins from the ischemic hemisphere with <1.0% false discovery rate. Data mining revealed that (1) about 2.7% of detected proteins were temporally perturbed having an involvement in the energy metabolism (Pygb, Atp5b), glutamate excitotoxicity (Slc1a3, Glud1), neuro-inflammation (Tf, C3, Alb), and cerebral plasticity (Gfap, Vim, Gap43); (2) astrocytes participated actively in the neurometabolic coupling underlining the importance of a cerebro-protective rather than a neuro-protective approach; and (3) hyper-acute yet progressive opening of the blood brain barrier (BBB), accompanied by stimulation of an innate immune response and late activation of a regenerative response, which provides an extended therapeutic window for intervention. Several regulated proteins (Caskin1, Shank3, Kpnb1, Uchl1, Mtap6, Epb4.1l1, Apba1, and Ube1x) novel in the context of stroke were also discovered. In conclusion, our result supports a dynamic multitarget therapy rather than the traditional approach of a unilateral and sustained modulation of a single target to address the phasic regulation of an ischemic proteome.

Killian-Jamieson (K-J) diverticulum is a rare cervical oesophageal diverticulum, less commonly encountered compared with Zenker's diverticulum (ZD). We report a case of K-J diverticulum in a 52-year-old lady who presented with sensation of lump in the neck and food stuck in the throat of 5 years duration. Esophagogram showed a large rightsided pharyngoesophageal diverticulum which was confirmed on endoscopy. The patient underwent a diverticulopexy and recovered without complications. Her symptoms had improved. In this report, we review the literature and describe our surgical technique.

Radiotherapy for uterine cervix carcinoma is an accepted treatment for all stages of invasive malignancy. The radiation modality is usually a combination of brachytherapy and external beam therapy for all except the most extensive tumours (stage IV--FIGO). Satisfactory results have been obtained in the Singapore General Hospital using low dose-rate radium applications in combination with cobalt teletherapy. Five year actuarial survival rates of 86.7% were obtained for FIGO stage I, 65.0% for stage II, 41.4% for stage III, 4.9% for stage IV with an overall rate of 54.0% for all stages. Corresponding 10-year rates were: 79.6%, 60.2%, 35.2%, 0% and 48.2%. Preliminary results of primary radiotherapy in 36 patients with cervical carcinoma treated by high dose-rate brachytherapy (microSelectron HDR) combined with 6MVP photons from a Siemens linear accelerator are presented. The patients were registered at the Mount Elizabeth Oncology Centre from November 1989 to December 1990 inclusive. The morbidity from high dose-rate therapy appears lower (9.1% for vaginal stenosis, 6.1% for non-severe proctitis) than for the radium series (4.1% and 20.8%) although the major complication rate appears similar (3% vs 2.8% respectively). The total failure rate is also lower at 19.4% for the HDR patients compared to 33.5% for the radium group. However, these rates are not strictly comparable as the HDR series consists of a small number of patients with limited follow-up. In the light of the data indicating acceptable morbidity with significant rate of early failure, the HDR brachytherapy doses have been increased whilst keeping within the limits set by other centres.

One hundred and forty-three patients (Group 1) with histologically proven nasopharyngeal-carcinoma (NPC) had bone scintigraphy with 99Tcm methylenediphosphonate (MDP) or dihydroxypropanediphosphonate (DPD) within 2 months of the initial diagnosis. A further 162 patients (Group 2) had bone scans during the course of follow-up if there were symptoms of bone pain or evidence of metastases at other sites. Twenty-three per cent (33/143) of the newly diagnosed NPC patients (Group 1) had evidence of bone metastases. Of these 143 patients, 101 were T0-T2, 16 were T3 and 25 were T4. Thirty-six patients had no neck nodes (NO), 44 were N1, 25 N2 and 38 N3. Of the 162 patients in Group 2, 96 (59%) had a positive bone scan. The commonest sites for bony metastases from NPC were the spine, ribs, pelvis and lower limbs in order of frequency. There is a highly significant association with the nodal stage but no association with the UICC T staging which is not adequate in nasopharyngeal carcinoma. In our part of the world, bone metastases from NPC are a common cause of an abnormal bone scan.

A total of 363 cases of nasopharyngeal carcinoma (NPC) in Singapore were classified into squamous cell carcinoma (SCC; 73 cases), non-keratinizing carcinoma (NKC; 178 cases) and undifferentiated carcinoma (UC; 172 cases). Possible biological differences between these histologic types and between tumors with and without lymphocytic infiltration were investigated by correlations with survival rates and with selected epidemiologic, immunovirologic, and immunogenetic data on the disease. The 5-year survival rates following radiotherapy were 25.3% for all cases and 58.8% for tumors restricted to the nasopharynx. The 5-year survival rate for SCC was poorer than for the combined NKC and UC groups (p less than 0.05). The 3-year survival rate was better for tumors with lymphocytic infiltration (p less than 0.05), but there were no differences in the 5-year survivals. The survival rates were better in females (p less than 0.01) and in the younger age groups (p less than 0.01). There were no significant correlations between histopathology of NPC and the distributions of cases by age, sex, HLA antigen profiles, or cell-mediated immune status. Squamous cell carcinoma was associated with lower levels of antibodies to the Epstein-Barr nuclear antigen (p less than 0.05), but there were no differences with respect to antibodies against other EBV related antigens. These findings support the view that SCC, NKC, and UC of the nasopharynx, as defined in the WHO classification, are variants of a fairly homogeneous group of neoplasms in the Singapore population.

The results of 322 patients with uterine cervix carcinoma treated by radiotherapy at the Singapore General Hospital in the 3-year period from 1973 to 75 are presented. Two hundred seventy-nine patients were treated with a combination of intracavitary radium, using Fletcher-Suit applicators and cobalt teletherapy; the remaining 43 patients received only cobalt teletherapy. One hundred thirty-four patients (41.6%) presented with FIGO Stage III disease. Only 46 patients (14.3%) presented with Stage I disease, showing that patients tended to present late in the disease course. Five-year actuarial (uncorrected) survival rates of 86.7% for Stage I, 65.0% for Stage II, 41.4% for Stage III and 4.9% for Stage IV were obtained with corresponding 10 year rates of 79.6%, 60.2%, 35.2% and 0%. The overall 5 and 10 year survival rates were 54.0% and 48.2%, respectively. The survival rates "flattened off" at about 7-8 years, reflecting late deaths after the fifth anniversary of treatment. Non-severe complications consisted mainly of chronic proctitis (41.3%) and vaginal stenosis (20.8%). Major complications were intestinal stricture (1.2%) and fistula formation (1.6%).

Three hundred and fifty-two consecutive cases of nasopharyngeal carcinoma were analysed to determine the pattern of distant metastases. Diagnosis of distant metastases was made wholly on clinical signs and radiography. Ninety-nine patients developed distant metastases, an incidence rate of 28.1%. There did not appear to be any difference in "risk" by age or sex. The predilection of this cancer to develop skeletal metastases is further confirmed. Pulmonary and hepatic involvement were the next commonest. Both extent of primary tumour (T) and cervical lymph node status (N) exerted a significant influence on the probability of metastases developing. Thus significant differences in metastatic rate were observed between T0/T1, T2 and T3/T4 and N0, N1, N2 and N3 groups. 65.6% of metastatic cases had control of local disease (nasopharynx and cervical lymph nodes). When metastases are diagnosed the prognosis is gloomy with a median survival under four months and a fatality rate of 91% within a year of first metastasis.

Newly diagnosed NPC patients were found to have impaired general T-cell functions, as determined in vivo by the Mantoux test and in vitro by the PHA response assay. Treated remission patients were as hyporesponsiveness as newly diagnosed patients. PHA hyporesponsiveness was associated with the HLA profile of A2-B Sin 2 and with high antibody titres to EBV-related antigens, in particular to the early antigen. Impaired responses in the Mantoux or PHA tests were associated with poor survival. The impaired response could be partially or totally restored by in vitro treatment of the hyporesponsive lymphocytes with levamisole.

The management of patients with osteosarcoma in Singapore has for many years been an unrewarding task for the attending physicians. Encouraged by reports of long-term survivals with adjuvant cytotoxic chemotherapy appearing in 1975, orthopaedic surgeons and radiation therapists at the Singapore General Hospital undertook a program of combination chemotherapy in moderate doses for osteosarcoma patients with localised disease treated by ablative surgery. A few who refused surgery had irradiation of the primary tumour.

In 1971, 21 new patients with malignant lymphoma were treated at the Therapeutic Radiology Department, Singapore General Hospital. 17 patients completed their courses of radiotherapy. Of the 17 patients given radical treatment, 5 were of Hodgkin's disease and 12 of Non-Hodgkin's disease. The 5-year survival for the group with Hodgkin's disease is 80% (4/5). The 5-year survival for the group with Non-Hodgkin's disease in 41.6% (5/12).

Distant metastases from lung cancer is a common occurrence in a common malignancy. Almost every organ may be involved but the extra-thoracic sites posing common clinical problems are brain metastases, cord compression, painful bone metastases or pathological fractures, nodal spread and liver involvement. A review of the records of 225 lung cancer patients referred to the Therapeutic Radiology Department, Singapore General Hospital, during the calender year 1985 showed a metastatic rate of 13.8% at referral. On subsequent follow up, an additional 49 patients (21.7%) developed metastases clinically. The organs involved were bone (21 patients), spinal cord (21 patients), brain (18 patients), liver (13 patients), other lung (7 patients) and other sites (17 patients). The management of metastases to the brain, bone and liver, and spinal cord compression will be discussed.

Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease.

This study analyses the results of primary radiotherapy for 44 patients with early glottic cancer (Tis, T1 stage) given at the Therapeutic Radiology Department, Singapore General Hospital during the 4-year period from 1978 to 1981. Irradiation was delivered using cobalt teletherapy with free set-ups, and without "air-gap" compensation. Total doses of 55Gy to 64Gy were given in daily fractions of 1.8Gy, treating five times a week. The crude 5-year survival rate for Tis/T1a tumours was 88.9% and for T1b lesions, 81%. On correcting for deaths from intercurrent disease, the survival rates improved to 95.5% and 92.6% respectively. In 33 cases where the quality of voice after radiation was assessed, 15 patients (45.4%) retained good voice quality with an additional 11 patients (33.3%) having acceptable voice quality. In seven cases the voice after radiation was rated as poor. Nine patients had local recurrence, giving a rate of 20.4%. One other patient had cervical node metastasis and subsequently developed lung secondaries. Surgery, solely or with re-irradiation, was an effective treatment for local recurrence. Re-irradiation alone failed to control any case with recurrence.

Nasopharyngeal Carcinoma is one of the most prevalent malignancies treated by radiotherapy in Singapore. Planning of the radiation fields for this condition is difficult because of the proximity of anatomical structures that are vulnerable to irradiation, such as the eyes, brain stem and cervical cord. However, the treatment results have shown progressive improvement. The treatment technique currently used utilized cobalt as well as caesium teletherapy units. Of the 104 cases treated in 1970 using this technique, the overall absolute 5 years survival rate with no evidence of disease is 30.8%. For Stage I cases, the rate is 62.5%. The prognosis is significantly better for the female than the male and is also related to age.

The use of hyperthermia together with radiotherapy in the treatment of relatively radioresistant tumours has been widely studied. In this preliminary non control study we used a 8MHz RF capacitive heating machine together with temperature probes inserted into the tumours under local anaesthesia. 27 patients with advanced post-radiation tumour recurrences as well as known radioresistant tumours were selected for treatment with hyperthermia and radiation. 7 patients withdrew from the study because of their intolerance to heat. 3 patients received superficial skin burns. Of the 20 patients studied, we were able to obtain moderate hyperthermia in most cases. 2 patients showed complete responses and 13 partial responses, giving rise to a total response rate of 75%. Some of the technical difficulties in achieving satisfactory hyperthermia are discussed. These include insertion of multiple probes into the body and the problem of achieving uniform heating of the tumour. Advances in hyperthermia can be expected with the development of improved methods of heat delivery and temperature measurements. However, presently methods of heat delivery can be improved by careful adjustment of the heating applicators and manipulation of cooling pads to avoid areas of excessive heating. Further clinical trials should be carried out to establish the optimum technique of hyperthermia.

Conservation treatment in carcinoma of the breast is a viable option in the West but is still an uncommon practice locally. Many reasons have been put forth, including the late stage of the tumour we see and the small breast size. This paper presents 25 cases treated by lumpectomy and irradiation with satisfactory cosmetic results, although the follow-up period is short. The introduction of this technique may encourage women to seek treatment earlier, without the fear of losing their breasts.

The results of 76 cases of advanced colorectal carcinoma treated at the Department of Therapeutic Radiology, Singapore General Hospital, from 1977 to 1978, are presented. All cases had "Curative" Surgery and were given adjuvant radiotherapy or chemotherapy or both. All were adenocarcinoma and had lymph node involvement as well as tumour infiltration through the bowel wall. 44 cases of rectal carcinoma were given radiotherapy to the pelvis followed by I/V 5-fluorouracil for at least one year. 32 cases of colon cancer were given I/V 5-fluorouracil for at least one year. 20 of these cases had cancer of the sigmoid colon and were given pelvic irradiation as well. The five year actuarial survival rates were 27.8% for rectal cancer and 24.3% for colon cancer.

A study was made on testicular leukaemia developing in children treated for leukaemia in the Department of Paediatrics, Singapore General Hospital over the past 6 years. Of the 44 cases of acute leukaemia treated, 24 were males, and 6 developed testicular leukaemia, all occurring in patients with acute lymphoblastic leukaemia. Half the cases developed testicular relapse while on chemotherapy with the other half developing it after all chemotherapy was stopped. There is a place for prophylactic radiotherapy to the testis. Testicular biopsy should be considered early in high risk groups.