Amniotic fluid gamma-glutamyl transferase for prediction of biliary atresia in cases of non-visualisation of the fetal gallbladder: a retrospective study using a validated analytical platform and local reference range.

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.

Efficacy, toxicities, and prognostic factors of stereotactic body radiotherapy for unresectable liver metastases.

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.

Outcomes of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

INTRODUCTION: Salvage radiotherapy (SRT) provides effective biochemical control for patients with prostate cancer who have prostate specific antigen (PSA) failure after radical prostatectomy. However, the effect of SRT on long-term clinical outcomes remains unknown. Therefore, we report the natural history of patients treated with SRT. METHODS: We identified 84 Chinese patients with prostate cancer treated with SRT to the prostatic fossa alone during 2006-2017 at Tuen Mun Hospital, Hong Kong. Survival was calculated using Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters with outcomes. RESULTS: Median SRT dose given was 70 Gy (range, 64-76 Gy). Median pre-SRT PSA level was 0.4 ng/mL (0.2-7.4 ng/mL). After SRT, 47 (56%) patients had undetectable (<0.1 ng/mL) PSA levels. After median follow-up of 48 months (2 months to 10 years), 25 (30%) patients had further biochemical progression. Subsequently, 12 patients received androgen deprivation therapy and nine (11%) developed distant metastasis. The 5-year biochemical progression-free survival, androgen deprivation therapy-free survival and metastasis-free survival were 62.7%, 83.5% and 86.7%, respectively. Early PSA failure after radical prostatectomy (hazard ratio 7.4), negative surgical margin (hazard ratio 2.7), positive extracapsular extension (hazard ratio 4.6), and detectable PSA levels after SRT (hazard ratio 17.3) were associated with lower biochemical progression-free survival after SRT. CONCLUSIONS: High-dose SRT with intensity-modulated radiotherapy/volumetric modulated arc radiotherapy is an effective local treatment that can prevent distant metastasis and avoid the need for androgen deprivation therapy in Chinese patients who have PSA failure after radical prostatectomy.

Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era - The Early and Late Effects of Radiation and Cisplatin.

AIMS: Hearing loss is a common debilitating complication in nasopharyngeal carcinoma (NPC) survivors. The aim of the present study was to investigate the impact of inner ear/cochlear radiation dose and cisplatin use on early and late sensorineural hearing loss (SNHL) in NPC patients treated with radiotherapy alone, concurrent chemoradiation (cCRT) and induction chemotherapy followed by cCRT (iCRT) in the intensity-modulated radiotherapy era. MATERIALS AND METHODS: The study included 81 NPC patients treated with intensity-modulated radiotherapy between 2014 and 2016. Pure tone audiometry was carried out at baseline and follow-up. The effects of cochlear/inner ear radiation and cisplatin doses on early (<12 months) and late (≥24 months) SNHL were analysed using multivariable regression after adjusting for important predictors. RESULTS: In total, 156 ears were examined. In early SNHL (n = 136), cisplatin use predicted the incidence of early high-frequency SHNL (HF-SNHL) (odds ratio 6.4, 95% confidence interval 1.7-23.9, P = 0.005). Ninety ears were analysed for late SNHL (median follow-up 38 months). Inner ear/cochlear radiation and cisplatin doses and better pre-treatment hearing were independent predictors of threshold change at 4 kHz. Every 10 Gy increase in inner ear/cochlear Dmean resulted in 5-dB and 6-dB threshold changes, respectively (cochlear Dmean: B = 0.005, 95% confidence interval 0.0004-0.009, P = 0.031; inner ear Dmean: B = 0.006, 95% confidence interval 0.001-0.010, P = 0.014). Cisplatin use was associated with late HF-SNHL (odds ratio 3.74, 95% confidence interval 1.1-12.3, P = 0.031). In the cCRT and iCRT subgroups, no cisplatin dose-dependent ototoxicity was observed. Severe (≥30 dB) late HF-SNHL occurred in 14% and 25% of the patients when the cochlear dose constraints were 40 Gy and 44 Gy, respectively. The radiotherapy-alone group did not develop severe late HF-SNHL. CONCLUSION: Cochlear/inner ear radiation dose and cisplatin use showed differential and independent ototoxicity in early and late SNHL. As cochlear/inner ear dose-dependent ototoxicity was demonstrated, the cochlear dose constraint should be as low as reasonably achievable, especially when cisplatin is also administered.

Solitary Parathyroid Adenoma Localization in Technetium Tc99m Sestamibi SPECT and Multiphase Multidetector 4D CT.

BACKGROUND AND PURPOSE: Minimally invasive parathyroid surgery relies critically on image guidance, but data comparing the efficacy of various imaging modalities are scarce. Our aim was to perform a blinded comparison of the localizing capability of technetium Tc99m sestamibi SPECT, multiphase multidetector 4D CT, and the combination of these 2 modalities (technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT). MATERIALS AND METHODS: We reviewed the records of 31 (6 men, 25 women; median age, 56 years) consecutive patients diagnosed with biochemically confirmed primary hyperparathyroidism between November 2009 and March 2010 who underwent preoperative technetium Tc99m sestamibi SPECT and multiphase multidetector 4D CT performed on the same scanner with pathologic confirmation by resection of a single parathyroid adenoma. Accuracy was determined separately for localization to the correct side and quadrant using surgical localization as the standard of reference. RESULTS: Surgical resection identified 14 left and 17 right parathyroid adenomas and 2 left inferior, 12 left superior, 11 right inferior, and 6 right superior parathyroid adenomas. For left/right localization, technetium Tc99m sestamibi SPECT achieved an accuracy of 93.5% (29 of 31), multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT achieved 96.8% accuracy (30 of 31). For quadrant localization, technetium Tc99m sestamibi SPECT accuracy was 67.7% (21 of 31), multiphase multidetector 4D CT accuracy was 87.1% (27 of 31), and technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT accuracy was 93.5% (29 of 31). Reader diagnostic confidence was consistently ranked lowest for technetium Tc99m sestamibi SPECT and highest for technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT. CONCLUSIONS: For left/right localization of parathyroid adenomas, all modalities performed equivalently. For quadrant localization, technetium Tc99m sestamibi SPECT + multiphase multidetector 4D CT is superior to technetium Tc99m sestamibi SPECT.

A pre-optimised dosimetry system using a rigid applicator for intracavitary treatment of cervical carcinoma.

AIMS: Tumour control and complication risk have been major concerns in the treatment of cervical carcinoma. A review of dose distribution for intracavitary treatment of cervical carcinoma revealed that modification of the Manchester dosimetry system is necessary for cases of narrow-sized vagina. A revised dosimetry system was introduced in the present study, with the objective of optimising the dose coverage for the parametrium while minimising the bladder and rectum dosage by restricting the rectal dose so as not to exceed 75% of the brachytherapy prescription dose. MATERIALS AND METHODS: A suitable-sized applicator was selected according to the patient's anatomy. The revised system is optimised based on the fixed geometry of the applicator. The system was therefore predefined and the distribution of the treatment dose already determined before application. The revised system was applied to 135 cases, involving 540 applications. The clinical outcome in terms of local tumour control and complication rates is reported. The differences between the revised system and the Manchester system in terms of dose coverage for the parametrium and the rectum dose were compared. RESULTS: The results showed that higher rectal and parametrial dosages were obtained with the Manchester system as compared with the revised system. Our study showed that over 50% of our patients would have received a rectal dose close to 100% of the point A dose if the Manchester system was applied, whereas it was restricted to below 75% using the revised system. Using the revised system, the significance of the parametrial dosage coverage in relation to local control was assessed: the mean dose to the rectum and the bladder as a percentage of point A was 65.7 +/- 5% (range 50-85%) and 66.4 +/- 14% (range 29-116%), respectively. The 5-year actuarial local failure-free survival rates were 90, 92.9, 86.8, 100, 69.7 and 0% for stages IB, IIA, IIB, IIIA, IIIB and IV (P < 0.0001), respectively. The 3-year actuarial complication rates (grade 3/4) for proctitis and cystitis were 1.4 and 0.5%, respectively. The dosage coverage for the parametrium was found to be significant (P = 0.029) in relation to local control for early-stage disease. CONCLUSIONS: The favourable local tumour control and low complication rates shown by our results indicate that the revised system presents an optimal dose distribution, particularly for the application of small ovoids, whereas morbidity was reduced to a lower level without compromising local control.

Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.

PURPOSE: To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS: We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS: One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION: In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Isolated limb perfusion in the sarcoma-bearing rat: a novel preclinical gene delivery system.

Reliable site-specific delivery of genetic constructs remains a challenging component of gene-based therapy of solid tumors. Isolated limb perfusion (ILP) continues to be evaluated for treatment of locally advanced soft tissue sarcomas because this approach uniquely directs therapeutic agents into the tumor-bearing extremity without significant systemic leak. In light of these considerations, we tested the hypothesis that ILP could be used to deliver genes carried in viral vectors to the sarcoma-bearing rat extremity, resulting in demonstrable gene transfer into the tumor. ILP was performed in rats by cannulating the femoral artery and vein, isolating the hind limb from systemic circulation by tourniquet, and cycling perfusate for 15 min at a rate of 2.4 ml/min. Leakage into the systemic circulation was 7.5% of the total perfusate concentrated in the isolated limb, as determined by perfusion with technetium 99m-tagged RBCs. We used the ILP technique to perfuse rat hind limbs bearing syngeneic fibrosarcoma tumor nodules with the replication-defective adenovirus Ad5LacZ, which expresses the bacterial beta-galactosidase. 5-Bromo-4-chloro-3-indolyl-beta-D-galactoside staining of the perfused limb tissues confirmed gene transfer to the tumor and peritumoral tissue, demonstrating that the tumor was part of the perfusion circuit and that gene therapy delivered via this method was feasible. These results suggest that adaptation of this preclinical gene delivery model to administer genetic constructs aimed at controlling tumor growth may prove beneficial to patients with extremity sarcomas.

Detecting recurrent or residual lung cancer with FDG-PET.

UNLABELLED: We investigated the diagnostic accuracy of FDG-PET in the detection of recurrent lung cancer. METHODS: Thirty-nine lesions in 38 patients with clinically suspected recurrent or residual lung cancer were studied with PET. All PET images were visually interpreted in conjunction with thoracic CT or MRI. Semiquantitative analysis using standardized uptake values (SUVs) was also performed in 25 lesions. FDG-PET diagnoses were correlated with pathological diagnoses and clinical outcome. RESULTS: The sensitivity and specificity of FDG-PET for detecting recurrent tumors were 100% (26/26) and 61.5% (8/13), respectively. The difference in mean SUV between recurrent tumors and noncancerous lesions was statistically significant [11.2 +/- 5.7 (n = 16) vs. 3.5 +/- 1.8 (n = 9), p < 0.0001]. False-positive results showed relatively lower SUVs than true-positives and also demonstrated increased uptake in a curvilinear rather than nodular shape. CONCLUSION: FDG-PET is useful for detecting recurrent lung cancer after treatment. False-positive diagnoses might be reduced by analysis of uptake shape and serial changes in SUV, but further study is needed.

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors.

UNLABELLED: Two commonly used tumor-seeking agents for PET are 2-deoxy-2-18F-fluoro-D-glucose (FDG) and L-methyl-11C-methionine (Met). This study compared FDG and Met in detecting residual or recurrent malignant tumors in the same patients. METHODS: Thirty-four lesions in 24 patients with clinically suspected recurrent or residual tumors were studied with PET using Met as well as FDG. FDG scans were conducted 1 hr after the completion of PET with Met. The color-coded superimposed images of standardized uptake values (SUVs) and transmission data were produced, and the peak SUVs in the lesions were then evaluated. Lesions above 2.5 SUV were interpreted as positive results for active tumor. RESULTS: The sensitivity of FDG-PET and Met-PET were 64.5% (20/31 lesions) and 61.3% (19/31 lesions), respectively. The mean SUV of FDG in residual or recurrent malignant tumors (n = 31) was significantly higher than that of Met but there was a significant correlation (r = 0.788, p < 0.01) between FDG and Met SUVs in all lesions (n = 34). CONCLUSION: PET using FDG and Met appear equally effective in detecting residual or recurrent malignant tumors although FDG uptakes were slightly higher than Met uptakes. Both showed a limited diagnostic sensitivity for small (< 1.5 cm) tumors.

Comparison of fluorine-18-FDG PET and technetium-99m-MIBI SPECT in evaluation of musculoskeletal sarcomas.

UNLABELLED: We compared the diagnostic accuracy of [18F]FDG PET and 99mTc-MIBI SPECT in musculoskeletal sarcomas. METHODS: Forty-eight patients with clinically suspected recurrent or residual musculoskeletal sarcomas were examined with both FDG-PET and MIBI-SPECT within 2 wk of each study (one follow-up study in nine patients and we follow-up studies in one patient). Imaging findings were visually inspected with grading scales in conjunction with CT and/or MRI, and count-density ratios of lesion-to-contralateral area and standard uptake values (SUVs) of FDG and MIBI in lesions were also generated. The results were correlated with histologic findings (in 51 studies) and/or long-term follow-up evaluations. RESULTS: The diagnostic sensitivities and specificities were 98% and 90% using FDG, and 81.6% and 80% using MIBI, respectively, with statistical significance in the sensitivity. The tumors were demonstrated better in FDG studies, which produced higher visual grades (2.1 versus 1.6), and the tumors showed increasing SUVs with time (from 6.3 to 7.3). Four of nine patients with positive FDG but negative MIBI scans failed to respond to multidrug therapy. CONCLUSION: FDG-PET and MIBI-SPECT are useful in differentiating active sarcomas from post-treatment changes and in evaluating therapeutic response. MIBI-SPECT and FDG-PET findings should be interpreted in con junction with CT and/or MRI. FDG-PET shows statistically significant higher sensitivity than MIBI-SPECT. A positive FDG but negative MIBI scan might suggest a multidrug resistance.

Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer.

UNLABELLED: We retrospectively investigated the value of PET with fluorine-18 fluorodeoxyglucose (FDG) for preoperative chemotherapy response in patients with locally advanced breast cancer. METHODS: FDG-PET studies were performed on 16 consecutive patients. All patients had PET studies before chemotherapy, 13 patients between the end of the first cycle and at the midpoint of chemotherapy, and 14 patients before surgery. Visual diagnoses and the standardized uptake values (SUV) of PET scans were compared with pathology findings at surgery and with the results of mammography, ultrasonography (US) or both, which were performed before chemotherapy and before local surgery for residual disease. Each patient's clinical course was monitored for up to 3 yr. RESULTS: Sensitivity for detection of pathologically proven primary lesions was 100%, 62.5% and 87.5% with FDG-PET, mammography and US, respectively; and sensitivity for detection of initial nodal involvement was 77%, 70% and 87.5%, respectively. Sensitivity for detection of residual primary tumor was 75%, 71.4% and 87.5%, respectively; and sensitivity for detection of residual nodal involvement was 41.6%, 71.4% and 66.6%, respectively. The mean SUV value of primary lesions was 9.4 (range 2.0-20.7, n = 16), with only two lesions showing an SUV below 3. Clinical improvement of primary lesions was seen in all patients; improvement with smaller size and less FDG uptake was visible as early as the second study in 11 patients (69%). Mean SUV values obtained at the second and third studies decreased significantly from those obtained in the first study. In four patients, the disease recurred after breast surgery with high SUV values. The mammograms and sonograms obtained before surgery showed a decrease in the diameter of 6 and 12 primary lesions of the 13 and 14 patients examined, respectively. CONCLUSION: FDG-PET is valuable for monitoring the effects of preoperative chemotherapy in patients with locally advanced breast cancer with better sensitivity for primary tumor and better specificity for nodal metastasis in comparison with ultrasonography.

Correlation between bone scan findings and collagenase activities in patients with breast cancer.

RATIONALE AND OBJECTIVES: This study correlates nuclear bone scan findings and measurements of type IV collagenases for the evaluation of bony metastasis in patients with proven breast cancer. METHODS: The authors retrospectively evaluated the final diagnosis of a bone scan and the results of an immunohistochemical staining for 92 kDa and 72 kDa type IV collagenases in, respectively, 30 and 30 patients with metastatic breast cancer, and, respectively, 27 and 26 patients with primary breast cancer. The immunohistochemical staining was performed with tissue specimens obtained from a primary or metastatic breast tumor lesion. The amounts of the enzyme were graded from 0 to 4 and scored by multiplication with the percentage of tumor cells. The confidence of bone scan interpretation also was scored from 1 to 5 with increasing probability. RESULTS: There was a significant difference in enzyme scores between patients with and without metastases. Patients with < 170 92 kDa (26 of 27), 72 kDa (26 of 26) type IV collagenase, showed no active bony, lung, or liver metastases. However, there were variable bone scan findings in patients with a > 200 enzyme score. CONCLUSIONS: Bone scan provides no additional benefit in breast cancer patients with a type IV collagenase score of < 170. A bone scan is necessary to confirm, localize, or followup bony metastases in patients with an enzyme score of > 200.

In vitro culture--a method of pancreatic islet preservation for transplantation.

Pancreatic islets from adult rats, accumulated daily for a period of 2 wk, were cultured in artificial capillary culture units that were perfused with nutrient medium. Viability and functional capacity of these islets in this in vitro culture system has been shown to be maintained. The therapeutic efficiency of cultured islets was comparable to freshly isolated islets when assessed by transplantation into streptozotocin-induced diabetic rats. Intraportal implantation of either freshly isolated or cultured islets into isogeneic diabetic rats resulted in normal weight gain as well as complete reversal of hyperglycemia, glycosuria, and polyuria in the diabetic rat recipient. The normoglycemic state was sustained for more than 12 mo. Plasma glucose clearance rate (KG) were significantly lower in both the transplanted fresh or cultured islet groups than in the normal controls; however, the cultured islets were not less effective than the fresh islets. The results of the present study indicate the feasibility of accumulation of large numbers of islets in the in vitro culture system without any loss of therapeutic efficiency when implanted in vivo. Further improvement of this in vitro culture system can thus be applied in islet preservation for islet transplantation.

Middle cerebral artery blood flow velocity in patients with cirrhosis.

BACKGROUND: Brain dysfunction is common in patients with advanced liver disease; it is often manifested as hepatic encephalopathy, but its cause is not clearly understood. METHODOLOGY: Intracranial blood flow velocity parameters, including peak systolic velocity, end diastolic velocity and mean velocity of both middle cerebral arteries were measured by transcranial Doppler ultrasonography in 37 patients with cirrhosis without encephalopathy (16 Child's A, 10 Child's B and 11 Child's C) and 12 normal controls. The cause was alcohol-related in 24 and non-alcohol-related in 13. RESULTS: No significant differences in any of the Doppler parameters were detected in Child's group A when compared with controls. However, a statistically significant decrease in middle cerebral artery blood flow velocity was evident when Child's B and C patients without clinically apparent encephalopathy were compared with controls irrespective of the cause. Our results demonstrate that intracranial blood flow is abnormal in patients with advanced liver disease without clinically apparent encephalopathy.

Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study.

Positron emission tomography (PET) was used to assess the biodistribution and clinical usefulness of [18F]fluorotamoxifen (FTX) in 10 patients with estrogen-receptor(ER)-positive breast tumors. Ten patients with ER-positive breast cancer were prospectively studied, and the consecutive PET imagings (each takes 15 or 20 min) were obtained for 60 or 80 min after the injection of 88.8-392.2 MBq (2.4-10.6 mCi) of [18F]FTX. Twenty three suspected primary or metastatic lesions in 10 patients were evaluated and the tumor uptakes of [18F]FTX in nineteen tumor lesions were correlated to the response of tamoxifen therapy. Three lesions in three patients were considered to be truly negative for breast cancer on the bases of biopsy specimens and/or clinical course. Five (71.4%) of seven patients and 16 (80.0%) of 20 lesions were interpreted to be truly positive for breast cancer. The mean standardized uptake value (SUV) of the radiotracer in tumor was 3.0 on delayed images. There was no significant correlation between the standardized uptake values of [18F]FTX and the ER concentrations in primary lesions. Nineteen tumor lesions in six patients were evaluable to compare the [18F]FTX uptake with responses to tamoxifen therapy after the PET study. Three patients who had a good response to tamoxifen therapy showed positive lesions on PET images, whereas two of three patients who had a poor response showed negative lesions and one showed mixed results. There was no significant difference of [18F]FTX uptake in bone lesions between good and poor responders. However, when bone lesions were excluded, [18F]FTX uptakes in tumors with good responses were significantly higher than those with poor responses (mean and standard deviation of SUV: 2.46 +/- 0.62 vs 1.37 +/- 0.59, P < 0.05). PET imaging using [18F]FTX provides useful information in predicting the effect of tamoxifen therapy in patients with ER-positive breast cancer. Further study is warranted to confirm the clinical utility of PET using [18F]FTX in breast cancer patients.

Treatment results of endometrial carcinoma with positive peritoneal washing, adnexal involvement and serosal involvement.

AIMS: To review the treatment results of patients with endometrial carcinoma having positive peritoneal washing (PPW), adnexal involvement, uterine serosal involvement, or all three. MATERIALS AND METHODS: The treatment records of patients who had undergone primary surgery for endometrial cancer without distant metastasis during 1990--2001 at the Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, were reviewed. Thirty-five patients were found to have involvement of positive PPW, adnexal involvement, uterine serosal involvement, or all three. Seven (20%) of them had gross or microscopic lymph-node metastasis. Thirty-three (94.3%) patients received adjuvant radiotherapy (28 whole-pelvic irradiation [WPI]; five abdominal radiotherapy [WART]). Two patients with solitary ovarian metastasis received chemotherapy, and one with isolated PPW also received adjuvant hormonal therapy. The median follow-up was 50.4 months (range 2.4-151.2 months). Multivariate analysis was carried out using the Cox regression proportional hazards model. RESULTS: Among the 28 patients with clinical or pathological node-negative disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIA), only two patients with solitary ovarian metastases developed recurrence. The 5-year actuarial disease-free survival (DFS) rates for the whole group and patients without lymph-node involvement were 77.9% and 91.7%, respectively. Five out of the seven patients with lymph-node involvement developed recurrences. Univariate analysis showed that lymph-node involvement (P < 0.0001) and high-grade disease (P = 0.011) were the significant poor prognostic factors. Multivariate analysis showed that lymph-node involvement was the only significant poor prognostic factor to predict poor 5-year DFS (P = 0.0001). Only one patient (3.7%) who had received WART developed grade 4 toxicity. CONCLUSIONS: This study showed that good treatment results could be obtained from patients with stage IIIA endometrial carcinoma without clinical or pathological lymph-node involvement after adjuvant radiotherapy, with acceptable late side-effects. The relative prognostic importance of individual IIIA involvement and the optimal adjuvant treatment remain to be determined.

Small cell carcinoma of the cervix complicated by pregnancy.

We report the results of treatment in a 26-year old patient with stage IB2 small cell carcinoma of the cervix complicated by pregnancy. A pathological complete remission was achieved following sandwich chemotherapy and radiotherapy. The patient remains in clinical remission 14 months after presentation.