Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite identification.However,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples.The experimental CCS values,along with mass spectral properties,were reported for the 174 metabolites.The experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS values.Among the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of VLMs.The TWCCSN2 values were highly repeatable,with inter-day variations of<1%relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(DCCS)within±2%of the reported drift tube IMS(DTIMS)and TWIMS CCS values.The complexity of the urine matrix did not affect the precision of the method,as evidenced by DCCS within±1.92%.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of 1.Among these 55 metabolites,53(96%)were VLMs.The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients-a national cancer centre experience

Purpose or objective The COVID-19 pandemic has resulted in significant healthcare implications,with care for can-cer patients compromised due to resource diversion towards battling the pandemic.We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore,specifically via our nasopharyn-geal carcinoma(NPC)treatment data.This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore.The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy,time to staging scans,time to treatment commencement,due to its clear protocol and algorithms for staging and treatment;thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery.Materials and methods In this retrospective study,we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre.This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore,which may impact on healthcare seeking behaviour.Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays.Electronic medical records(EMR)were accessed.Only newly diagnosed NPC cases were included in our analysis.Patients with second synchronous primary malignancies or NPC disease recurrence were excluded.Data analysis was carried out using a combination of SPSS and Microsoft Excel.Results Significantly,there was a reduction of 37-46.3%in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years.Despite the reduction in numbers of newly diagnosed NPC,there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years.All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines.Conclusion We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time,encourage patient’s confidence in their ability to seek care.With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore,this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization.It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery,as well as survival outcomes.

Is nasopharyngeal cancer really a “Cantonese cancer”?

Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

Associations of lifestyle and diet with the risk of nasopharyngeal carcinoma in Singapore:a case–control study

Background: Nasopharyngeal carcinoma(NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population.Methods: We conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age(±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices.Results: After adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios(ORs) of 4.50(95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52(95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18(95% CI 1.69–10.38; P = 0.002).Conclusion: Smoking(currently and ever-smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.

Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma:A critical appraisal of the evidence

AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas(HCC).METHODS A systematic review of the published literature was performed using the PubM ed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer(BCLC) stage B or C HCC. The primary end point was to determine the overall survival(OS) and disease free survival(DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve(i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC(defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to(1) BCLC stage B or C HCC,(2) Size of HCC and(3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7%(range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0%(range 0.0-42.0). The collective median 5-year OS of both stages was 27.9%(0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR(95%CI) = 1.00(0.76-1.31)] and mortality [RR(95%CI) = 1.15(0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.

Awakening immunity against cancer:a 2017 primer for clinicians

Cancer immunotherapy has finally joined the pillars of cancer treatment-surgery, radiation, chemotherapy, hormonal therapy, and targeted therapy-in improving cancer patient lives. In the last 5 years, the development of immune checkpoint inhibitor and T cell therapy, particularly chimeric antigen receptor(CAR) T-cell therapy, has been remarkable for the speed, scale, and number of drug approvals. Still, these treatments may also bring unusual adverse effects and clinical outcomes including unprecedented long-term survival. Interrogating the tumor microenvironment and identifying better biomarkers hold the key to improving cancer immunotherapies. CAR T-cell therapy has dramatic effect on leukemias and lymphomas with significant cure rates, but has yet to show comparable effect on solid tumors. Cutting-edge technology will improve both processing and clinical effect of such therapies. Asia has the largest, most rapidly aging population and the largest number of cancer patients in the world. Research and development and clinical trial conduct of cancer immunotherapy in Asia remain nascent, but should be a crucial priority.

Nasal metastases from renal cell carcinoma are associated with Memorial Sloan-Kettering Cancer Center poor-prognosis classification

Unusual sites of metastases are recognized in patients with renal cell carcinoma (RCC). However, the prognostic implications of these sites are not well understood. We used the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification for metastatic RCC to evaluate 912 consecutive patients with RCC managed at the Singapore General Hospital between 1990 and 2009. Among these patients, 301 had metastases either at diagnosis or during the course of illness. Nasal metastases, all arising from clear cell RCC, were identified histologically in 4 patients (1.3% of those with metastasis). All 4 patients were classified as MSKCC poor prognosis by current risk criteria. Nasal metastases were significantly associated with lung and bone metastases. The frequency of nasal metastases in patients with metastatic RCC is about 1%, occurring predominantly in patients with clear cell RCC. Nasal metastases are associated with poor prognosis as estimated by the MSKCC risk classification, with attendant implications for selection of targeted therapy, and are usually associated with multi-organ dissemination, including concurrent lung and bone involvement.

^(68)Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts.There is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad P.Methods: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with CWU.Results: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT alone.Conclusions: In the present report, we demonstrated the diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

High incidence of nasopharyngeal cancer: similarity for 60% of mitochondrial DNA signatures between the Bidayuhs of Borneo and the Bai-yue of Southern China

Populations in Southern China (Bai-yue) and Borneo (Bidayuh) with high incidence of nasopharyngeal cancer (NPC) share similar mitochondrial DNA signatures, supporting the hypothesis that these two populations may share the same genetic predisposition for NPC, which may have first appeared in a common ancestral reference population before the sea levels rose after the last ice age.

Management of synchronous lateral pelvic nodal metastasis in rectal cancer in the era of neoadjuvant chemoradiation: A systemic review

BACKGROUND Lateral pelvic lymph node(LLN)metastasis(LLNM)occur in up to 28%of patients with low rectal tumours.While prophylactic lateral pelvic lymph node dissection(LLND)has been abandoned by most western institutions in the era of neoadjuvant chemoradiation therapy(CRT),the role of selective LLND in patients with enlarged LLN on pre-CRT imaging remains unclear.Some studies have shown improved survival and recurrence outcomes when LLNs show"response"to CRT.However,no management algorithm exists to differentiate treatment for"responders"vs"non-responders".AIM To determine if selective LLND in patients with enlarged LLNs results in improved survival and recurrence outcomes.METHODS A systemic search of Pub Med and Embase databases for studies reporting on patients with synchronous radiologically suspicious LLNM(s-LLNM)in rectal cancer receiving preoperative-CRT was performed.RESULTS Fifteen retrospective,single-centre studies were included.793 patients with sLLNM were evaluated:456 underwent TME while 337 underwent TME with7,LLND post-CRT.In the TME group,local recurrence(LR)rates range from 12.5%to 36%.Five-year disease free survival(DFS)was 42%to 75%.In the TME with LLND group,LR rates were 0%to 6%.Five years DFS was 41.2%to 100%.Radiological response was seen in 58%.Pathologically positive LLN was found in up to 94%of non-responders vs 0%to 20%in responders.Young age,low tumour location and radiological non-response were associated with final positive LLNM and lowered DFS.CONCLUSION LLND is associated with local control in patients with s-LLNM.It can be performed in radiological non-responders given a large majority represent true LLNM.Its role in radiological responders should be considered in selected high risk patients.

Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience

BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.

Two Cancers Arising from Different Mesenchymal Origins: An Unexpected Connection over Time and Space

Sarcomas are rare tumours, accounting for 1% of all malignancies. They are histologically diverse, presenting with more than 50 different subtypes. Sarcoma can be broadly divided into two categories—soft tissue sarcoma and bone sarcoma. Extraskeletal osteosarcoma is a unique subtype which is histologically similar to bone osteosarcoma but resides within soft tissue and has no attachments to bone. We present a rare case of a patient who initially presented with an extraskeletal osteosarcoma that was complicated by a chronic chest wall sinus and lymphedema of the left arm. He later developed enlarging left chest wall nodules at the same region that were proven to be dedifferentiated liposarcoma on biopsy 20 years later. We examine the occurrence of both extremely rare diseases of differing pathologies over the same site but separated by an extraordinarily long interval, and possible new associations to account for this phenomenon.

International consensus guidelines on robotic pancreatic surgery in 2023

Background:With the rapid development of robotic surgery,especially for the abdominal surgery,robotic pancreatic surgery(RPS)has been applied increasingly around the world.However,evidence-based guidelines regarding its application,safety,and efficacy are still lacking.To harvest robust evidence and comprehensive clinical practice,this study aims to develop international guidelines on the use of RPS.Methods:World Health Organization(WHO)Handbook for Guideline Development,GRADE Grid method,Delphi vote,and the AGREE-II instrument were used to establish the Guideline Steering Group,Guideline Development Group,and Guideline Secretary Group,formulate 19 clinical questions,develop the recommendations,and draft the guidelines.Three online meetings were held on 04/12/2020,30/11/2021,and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts.All the experts focusing on minimally invasive surgery from America,Europe and Oceania made great contributions to this consensus guideline.Results:After a systematic literature review 176 studies were included,19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence.Conclusions:The international RPS guidelines can guide current practice for surgeons,patients,medical societies,hospital administrators,and related social communities.Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

The roles and mechanisms of SREBP1 in cancer development and drug response

Cancer occurrence and development are closely related to increased lipid produc-tion and glucose consumption.Lipids are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and metastasis.Sterol regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid synthesis.In addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly cancer.However,no review of sREBP1 in cancer biology has yet been published.Herein,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ferroptosis.Addition-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

老年癌症患者的免疫治疗

癌症常见于老年人。初诊为恶性肿瘤的患者的中位年龄为66岁,癌症相关死亡的中位年龄为72岁[1]。老年人是癌症患病率增长最快的人群之一[2]。免疫治疗的发展,尤其是免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的问世,彻底改变了所有年龄层包括老年人在内的肿瘤患者的常规治疗方案。细胞毒性T淋巴细胞相关抗原4、程序性死亡受体1(programmed death receptor-1,PD-1)及其配体(programmed death-ligand 1,PD-L1)的抑制剂可改善多种肿瘤患者的总生存期(overall survival,OS)[3],且部分患者可获得持续缓解[4]。

Central hepatectomy for centrally located malignant liver tumors: A systematic review

AIM: To study whether central hepatectomy(CH) canachieve similar overall patient survival and disease-freesurvival rates as conventional major hepatectomies ornot.METHODS: A systematic literature search was per-formed in MEDLINE for articles published from January1983 to June 2013 to evaluate the evidence for andagainst CH in the management of central hepatic malig-nancies and to compare the perioperative variables andoutcomes of CH to lobar/extended hemihepatectomy. RESULTS: A total of 895 patients were included from21 relevant studies. Most of these patients who un-derwent CH were a sub-cohort of larger liver resectionstudies. Only 4 studies directly compared Central vshemi-/extended hepatectomies. The range of opera-tive time for CH was reported to be 115 to 627 min andPringle's maneuver was used for vascular control in themajority of studies. The mean intraoperative blood lossduring CH ranged from 380 to 2450 mL. The reportedmorbidity rates ranged from 5.1% to 61.1%, the most common surgical complication was bile leakage and the most common cause of mortality was liver failure. Mor-tality ranged from 0.0% to 7.1% with an overall mor-tality of 2.3% following CH. The 1-year overall survival(OS) for patients underwent CH for hepatocellular car-cinoma ranged from 67% to 94%; with the 3-year and 5-year OS having a reported range of 44% to 66.8%, and 31.7% to 66.8% respectively. CONCLUSION: Based on current literature, CH is a promising option for anatomical parenchymal-preserv-ing procedure in patients with centrally located liver malignancies; it appears to be safe and comparable in both perioperative, early and long term outcomes when compared to patients undergoing hemi-/extended hepatectomy. More prospective studies are awaited to further define its role.

Radiation-induced sarcomas of the head and neck

With improved outcomes associated with radiotherapy, radiation-induced sarcomas(RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stagematched sarcomas that arise independent of irradiationand surgical resection with clear margins seems to offer the best chance for cure.

An Overview of Carbon Nanotubes and Graphene for Biosensing Applications

With the development of carbon nanomaterials in recent years, there has been an explosion of interests in using carbon nanotubes(CNTs) and graphene for developing new biosensors. It is believed that employing CNTs and graphene as sensor components can make sensors more reliable, accurate, and fast due to their remarkable properties. Depending on the types of target molecular, different strategies can be applied to design sensor device. This review article summarized the important progress in developing CNT-and graphene-based electrochemical biosensors, field-effect transistor biosensors, and optical biosensors. Although CNTs and graphene have led to some groundbreaking discoveries, challenges are still remained and the state-of-the-art sensors are far from a practical application. As a conclusion, future effort has to be made through an interdisciplinary platform, including materials science, biology, and electric engineering.