Monte Carlo study of PbSe quantum dots as the fluorescent material in luminescent solar concentrators.

In this paper, Monte Carlo simulations were performed to determine the potential efficiencies of luminescent solar concentrator (LSC) systems using PbSe quantum dots (QDs) as the active fluorescent material. The simulation results suggest that PbSe QD LSCs display good absorption characteristics, but yield limited LSC power conversion efficiency due to self-absorption and down-conversion loss. It is proposed that the self-absorption loss can be reduced by utilizing Förster resonance energy transfer between two different sizes of PbSe QDs, yielding pronounced improvement in the optical efficiency of LSCs.

Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer.

PURPOSE: To assess known cancer biomarkers CA-125, human tissue kallikreins KLK6 and KLK10, hemostatic markers and age with 5-year survival outcome from epithelial ovarian cancer. METHODS: Forty-one benign cyst cohorts and 83 patients diagnosed with ovarian cancer were recruited. The following assays were performed: fibrinogen, vWF antigen, D: -dimer, ATIII activity, tPA, PAI-1, uPAR, KLK6, KLK10 and CA-125. Follow-up visits of cancer patients of more than 60 months were noted. Data between those who survived past 60 months and mortality from cancer were analyzed. RESULTS: Only 24 patients lived past 60 months, and 31 died (advanced stage n = 27). Those living past 60 months were significantly older and associated with similar pre-operative levels seen in benign cyst cohorts especially for KLK6, fibrinogen, vWF, AT levels despite upregulation of D: -dimer, CA-125 and KLK10. Ovarian cancer cohorts living past 60 months were younger than those who died within 12 months (n = 12). Mortality within 12 months was associated with older age, upregulation of KLK6, fibrinogen, D: -dimer, vWF, tPA antigen and reduced ATIII levels. Similarly, mortality within 36 months of disease showed older age with upregulation of CA-125, KLK6 D: -dimer vWF antigen and tPA antigen levels. Late stage cancer (III/IV) showed upregulated CA-125, KLK6, KLK10, D: -dimer and reduced AT compared to early stage cancer (I/II). The 5-year survival rate for early cancer was 80%, advanced 22.9% and overall 5-year survival rate was 43.6%. CONCLUSION: Older age together with the novel biomarkers studied and their association with adverse outcome from epithelial ovarian cancer was seen especially within 12 and 36 months of disease. Those who lived past 60 months of disease showed similar pre-operative levels seen in benign cyst cohorts despite elevated D: -dimer, CA125 and KLK 10. An enlarged study is needed to confirm these findings.

Does initial routine use of a compression garment reduce the risk of lower limb lymphedema after gynecological cancer treatment? A randomized pilot study in an Asian institution and review of the literature.

This is a randomized pilot study evaluating the effectiveness of customized compression garments (CG) in reducing the risk of lower limb lymphedema (LLL) in gynecological cancer patients. Patients who completed pelvic node dissection or radiation were routinely educated on reducing the risk of LLL by good skin care and manual lymphatic massage. After baseline lower limb volume perometry and clinical assessment, they were randomized to customized compression garment (CG) for 6 weeks (26 patients) or observation (30 patients). Both groups were followed up for 2 years and the primary outcome was the development of LLL. LLL incidence in the control group was 13.3% (4 of 30 patients) compared to 7.7% (2 of 26 patients) in the CG group. However the difference was not statistically significant (P=0.496). In the control group, 10.7% (3/28) who underwent node dissection developed LLL vs 7.7% (2/26) in the CG group. Among patients with node dissection plus radiation, LLL incidence was 14.3% (1/7) in the control group vs 12.5% (1/8) in the CG group. The mean onset of LLL was 12 months; compliance to CG wearing was high and QOL scores were similar in both groups. Customized low-compression CG worn for 6 weeks may have a possible benefit in reducing the risk of LLL when added to patient education on risk reduction although statistic significance was not achieved in this small pilot study. A larger multi-center study would be justified to expand these findings.

Malignant ovarian germ cell tumors: the KK Hospital experience.

Ovarian germ cell malignancies pose a therapeutic challenge especially amongst young patients. This is a retrospective review of 49 patients treated for such malignancies at KK Women's and Children's Hospital over a 13-year period. The relative proportion of such tumors was 6.2%. Age at presentation ranged from 14 to 51 years (mean 25.4 years). Forty-nine percent of tumors were immature teratomas and 81.6% had stage I disease. All patients had surgery initially and 67.3% required postoperative adjuvant chemotherapy. The patients were followed-up for one to 145 months (mean 51.6 months). All the 87.8% of patients on follow-up are alive and disease-free. There was one recurrence. Five patients had eight successful pregnancies, with no congenital anomalies. Mean duration when menstruation was resumed and regular was 2.5 and 3.5 months, respectively. With combination chemotherapy and conservative surgery, the outlook for patients is excellent, with emphasis on preservation of ovarian function and fertility.

A rare case of metastatic ovarian carcinoma originating from primary intrahepatic cholangiocarcinoma. Case report.

BACKGROUND: A rare case of metastatic ovarian carcinoma arising from intrahepatic cholangiocarcinoma is reported and the literature reviewed. CASE: A 49-year-old woman presented with ascites and a left pelvic mass. Optimal debulking surgery was carried out including a segmental resection of segment 5/6 of the liver. Histopathology confirmed an intrahepatic cholangiocarcinoma metastatic to the ovaries and omentum. CONCLUSION: Distinguishing a metastatic tumor from a primary ovarian tumoris critical for appropriate management. A high index of suspicion intraoperatively and subsequent expert pathological review are essential in making the correct diagnosis.

Eclampsia--are we doing enough?

OBJECTIVES: This paper reviews the cases of eclampsia managed at the Kandang Kerbau Hospital with respect to incidence, management, maternal and perinatal outcome. METHOD: A retrospective analysis of eclampsia occurring over a 4-year period from January 1990 to December 1993. RESULTS: There were 27 cases of eclampsia among 59,599 deliveries during the study period, giving an overall incidence of 45.3 per 100,000 deliveries. Sixteen patients were nulliparous and the mean age was 29 years. Two-thirds of the cohort were booked patients and more than half of the cohort (55.6%) had their first seizure despite being in hospital. The majority (86.2%) of all seizures recorded occurred in the antepartum and intrapartum period. Eleven of the patients (40.7%) were asymptomatic prior to the first fit while headache was the commonest symptom of impending eclampsia in the remainder. Fifteen patients (55.6%) had significant proteinuria and this was associated with significant neonatal morbidity. The mean gestational age was 35.9 weeks and the mean birth weight was 2,328g. Major areas of substandard management included failure to administer anticonvulsant prophylaxis and antihypertensive agents when indicated, failure to assess for proteinuria, and failure to closely monitor the hypertensive and proteinuric patient. Seven patients developed convulsions despite anticonvulsant prophylaxis. Twenty-four patients were delivered by Caesarean section. There were 26 live born infants (singletons) and one abortus. There was no perinatal mortality. Neonatal morbidity was frequent and attributable to prematurity (51.9%) and birth asphyxia (29.6%). The majority of infants were well neurologically on long term follow-up. There was no maternal mortality but significant morbidity was present in 8 patients (29.6%). High uric acid levels were associated with intrauterine death, prematurity and intrauterine growth retardation. Seven patients remained hypertensive on follow-up. Residual neurological deficits persisted in 3 patients. CONCLUSIONS: The incidence of eclampsia at Kandang Kerbau Hospital shows an unsteady decline over the past 4 years. It carries significant foetal mortality (3.7%) as well as neonatal (74.1%) and maternal (29.6%) morbidity. The observation that neither the occurrence of antenatal office visits nor hospitalisation prevents eclampsia, and that substandard management was identified in most of the cases (77.8%) shows that there is no room for complacency and that more needs to be done. Improvement in patient assessment, institution of appropriate preventive therapy, a high index of suspicion even in apparently low-risk patients coupled with a disease notification system and regular audit may be the key strategies to reduce the incidence of this dreaded obstetric complication.

The role of urodynamics in evaluating incontinent females.

A total of 84 patients had urodynamic evaluations. Twenty-two patients complained of stress incontinence, 41 patients complained of stress incontinence with other urinary symptoms and 21 complained of other urinary symptoms but not stress incontinence. Of those complaining of stress incontinence alone, 4 (18.2%) had detrussor instability, 11 (50%) had genuine stress incontinence and 7 (31%) had neither condition. Of those complaining of stress incontinence with other symptoms, 16 (39%) had detrussor instability, 19 (46.3%) had stress incontinence and 6 (14.6%) had neither condition. Of those complaining of other urinary symptoms except stress incontinence, 5 (23.8%) had detrussor instability, 3 (14.3%) had stress incontinence and 13 (61.9%) had neither condition. Urinary symptoms were found to have little correlation with the final diagnosis except for enuresis which was associated with detrussor instability.

Endometrioid adenocarcinoma of the uterus: surgico-pathological correlations and role of pelvic lymphadenectomy.

INTRODUCTION: In 1988, FIGO added lymph node surgery to the staging system for endometrial cancer. This change remains controversial to date. From our study we aim to determine the significance of surgico-pathological parameters of endometrioid carcinoma for pelvic nodal metastases and survival, as well as to study the role of pelvic lymphadenectomy in the surgical treatment of this disease. MATERIALS AND METHODS: A retrospective study was conducted in 198 women with endometrioid carcinoma who underwent full surgical staging including pelvic lymphadenectomy. The multiple variant regression analysis and the multi-variant logistic regression analysis were applied in the analysis of relationship. RESULTS: A positive correlation between nodal metastases and grade, myometrial invasion, peritoneal cytology, adnexal involvement, lympho-vascular space involvement and tumour size was found. For survival, significant prognosticators were grade, myometrial invasion, peritoneal cytology, lympho-vascular space involvement, adnexal involvement, associated atypia and pelvic nodal metastases. Thirty-five per cent of the patients had high risk of recurrence based on uterine pathological factors but were node negative. They were spared external beam radiation and its associated morbidities, and were treated with adjuvant vault brachytherapy instead. Six per cent of the patients would have been understaged based on uterine factors alone if pelvic lymphadenectomy had not been done. CONCLUSION: We infer that routine pelvic lymphadenectomy should be considered for all surgically fit patients with endometrioid carcinoma. The accurate staging will allow individualized adjuvant therapy and prevent understaging and overtreatment.

FIGO stage 1B2 cervical carcinoma--the KK Women's and Children's Hospital experience.

INTRODUCTION: The objectives of this review were to document the surgico-pathological characteristics of surgically resected FIGO stage 1B2 cervical carcinoma and to review our overall experience with this disease. MATERIALS AND METHODS: This is a retrospective review of 35 patients diagnosed and treated from September 1990 to November 2001. RESULTS: The median age was 42 years and the mean tumour diameter was 5.1 cm. Majority were squamous cell carcinomas (65.7%), 28.6% were adenocarcinomas and 5.7% were adeno-squamous carcinomas. The primary treatment comprised radical surgery in 77.1%, radiotherapy in 20% and neoadjuvant chemotherapy followed by radical surgery and adjuvant radiotherapy in 2.9%. Significant surgico-pathological features noted were deep stromal invasion (66.7%), lympho-vascular space invasion (55.6%), parametrial involvement (22.2%), positive margins (3.7%) and pelvic node metastases (33.3%). Postoperative radiation was given to 92.6% of the patients who underwent primary surgery, of whom 29% received concurrent chemotherapy. Radiation toxicity was mild with no grade 3 or 4 toxicity documented. For the patients who had surgery, the recurRence rate was 14.8% (11.1% pelvic and 3.7% distant) and the survival rate was 88.9%. For those who had primary radiation, the rate of persistent disease was 28.6%, the distant recurrence rate was 28.6% and the survival rate was 57.1%. CONCLUSION: FIGO stage 1B2 cervical carcinomas are associated with significant rates of adverse surgico-pathological features. The ideal primary treatment is yet to be established and should be determined by prospective randomised trials.

An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530).

The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise. Different degrees of epithelial-mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others. Numerous studies have focused on bona fide epithelial and mesenchymal states but rarely on intermediate states. In this study, we describe a model system for appraising the spectrum of EMT using 43 well-characterised OC cell lines. Phenotypic EMT characterisation reveals four subgroups: Epithelial, Intermediate E, Intermediate M and Mesenchymal, which represent different epithelial-mesenchymal compositions along the EMT spectrum. In cell-based EMT-related functional studies, OC cells harbouring an Intermediate M phenotype are characterised by high N-cadherin and ZEB1 expression and low E-cadherin and ERBB3/HER3 expression and are more anoikis-resistant and spheroidogenic. A specific Src-kinase inhibitor, Saracatinib (AZD0530), restores E-cadherin expression in Intermediate M cells in in vitro and in vivo models and abrogates spheroidogenesis. We show how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS). We conclude that the characterisation of intermediate EMT states provides a new approach to better define EMT. The concept of the EMT Spectrum allows the utilisation of EMT genes as predictive markers and the design and application of therapeutic targets for reversing EMT in a selective subgroup of patients.

Ovarian tumors of borderline malignancy: a review of 247 patients from 1991 to 2004.

Borderline ovarian tumors account for 15% of epithelial ovarian cancers and are different from invasive malignant carcinoma. Majority are early stage, occurring in women in the reproductive age group, where fertility is important. We reviewed retrospectively 247 such cases treated at the Gynaecological-Oncology Unit, KK Women's and Children's Hospital, between January 1991 and December 2004. The mean age was 38 years (16-89 years). Majority of the cases (92%) were FIGO stage I (Ia, 75%; Ib, 1%; and Ic, 16%). Seven (3.5%) patients were diagnosed as having stage II disease, six (2.5%) as stage IIIa, two (1%) as stage IIIb, and four (2%) as stage IIIc. Histological origin was as follows: mucinous (68%), serous (26%), endometrioid (2.6%), and clear cell (1.2%). Primary surgical procedures undertaken were as follows: hysterectomy with bilateral salpingo-oophorectomy (52%), unilateral salpingo-oophorectomy (33%), or ovarian cystectomy (15%). Adjuvant chemotherapy was administered in 13 patients (5.2% of cases), of which 4 patients were given chemotherapy only because of synchronous malignancies. There were six recurrences (2.4% of cases). Overall mean time to recurrence was 59 months. Recurrence rate for patients who underwent a primary pelvic clearance was 1.6% compared to fertility-sparing conservative surgery (3.3%; although P= 0.683). No significant difference was noted in recurrence and mortality between staged versus unstaged procedures. The overall survival rate was 98.0%. There were a total of five deaths (2.8%): three (1.5%) from invasive ovarian/peritoneal carcinoma and two from synchronous uterine malignancies. It appears that surgical resection is the mainstay of treatment, with conservative surgery where fertility is desired or pelvic clearance if the family is complete. Surgical staging is important to identify invasive extraovarian implants that portend an adverse prognosis. The role of adjuvant chemotherapy is not established.

Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed müllerian tumors of the uterus.

The role of adjuvant therapy for malignant mixed müllerian tumors of the uterus has not been established. Our aim was to review our experience with sequential adjuvant therapy using cisplatin and ifosfamide chemotherapy and radiotherapy after surgical staging. A retrospective study of 43 patients from 1995 to 2004 was undertaken. Survival was calculated using the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazard regression model was used to assess the effect of treatment on survival after adjustment for age and stage. Twenty-eight patients received adjuvant chemotherapy and 28 patients had adjuvant radiotherapy. Twenty-one patients underwent sequential adjuvant chemotherapy and radiotherapy. Tumor recurrence occurred in 14 patients at a median duration of 10 months. The overall 2- and 5-year survival was 64% and 60%, respectively. The 2- and 5-year survival for stage I and II diseases was both 95%, while the 2-year survival for stage III and IV diseases was 25%. Patients who underwent sequential adjuvant therapy had an improved survival compared with patients who did not follow the protocol (P= 0.024). Our results with sequential adjuvant therapy are encouraging and justify future randomized trials.

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases.

BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.

The inhibitory upstream open reading frame from mammalian S-adenosylmethionine decarboxylase mRNA has a strict sequence specificity in critical positions.

The upstream open reading frame (uORF) in the 5' leader of the mammalian mRNA encoding S-adenosylmethionine decarboxylase (AdoMetDC) serves as a negative regulatory element by suppressing translation of the associated downstream cistron. Certain changes in the amino acid sequence of the hexapeptide (sequence MAGDIS) encoded by the uORF destroy suppressive activity, implying specific interaction with a cellular target. In this paper, we examine the extent of alterations that can be tolerated in this uORF. The mammalian AdoMetDC uORF inhibits downstream translation when placed into the 5' leader of a yeast mRNA with characteristics resembling those in mammalian cells, suggesting that the encoded peptide has a similar target across species. Using yeast for the initial screen, we tested the specificity of the critical three codons at the 3' end of the uORF by saturation mutagenesis. Altered uORFs selected from the primary yeast screen were then retested in mammalian cells. The requirements at codons 4 and 5 were quite stringent; only aspartic acid at codon 4 yielded a fully suppressive peptide, and only valine could substitute productively for isoleucine at codon 5. The specificity at codon 6 was much looser, with many substitutions retaining suppressive activity in both yeast and mammalian cells.

Pt L-edge XANES as a probe of Pt clusters.

The sensitivity of Pt L-edge XANES to local geometric and electronic structure in various Pt(n) clusters is investigated using the ab initio self-consistent FEFF8 code. Calculations based on FEFF8 are found to be in good agreement with experiment. For pure Pt clusters the XANES can distinguish between 2- and 3-dimensional clusters. Self-consistency is important in determining the variation of XANES with cluster size. The effect of a support is also studied. In Pt-Cl(x) clusters the presence of a Cl-Pt bond leads to a "hybridization peak," i.e., a peak in the Cl d-density of states (d-DOS) mixed with Pt d-states. For Pt-H clusters hydrogen addition is well correlated with the growth of a broad shoulder on the white line. This change is attributed largely to AXAFS, i.e., to a corresponding change in the atomic background absorption.