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1.
Nat Biomed Eng ; 7(2): 135-148, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36303008

RESUMO

The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules.


Assuntos
Vesículas Extracelulares , Hidrogéis , Humanos , Anticorpos , Vidro , Ouro
2.
Nat Commun ; 12(1): 4039, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193867

RESUMO

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration - spatial organization and distribution - in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/métodos , Neoplasias Colorretais/diagnóstico , Vesículas Extracelulares/metabolismo , Estruturas Metalorgânicas/química , Nanoestruturas/química , Tensoativos/química , Ascite/metabolismo , Neoplasias Colorretais/metabolismo , Glicosilação , Humanos , Prognóstico
3.
Eur J Surg Oncol ; 47(11): 2888-2892, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34020808

RESUMO

INTRODUCTION: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. MATERIALS AND METHODS: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. RESULTS: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. CONCLUSION: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.


Assuntos
Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/terapia , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Colorretais/patologia , Terapia Combinada , Humanos , Mitomicina/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Peritoneais/secundário , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários
4.
Sci Adv ; 6(19): eaba2556, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32494726

RESUMO

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

5.
Sci Rep ; 10(1): 682, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959771

RESUMO

Generation of large amounts of genomic data is now feasible and cost-effective with improvements in next generation sequencing (NGS) technology. Ribonucleic acid sequencing (RNA-Seq) is becoming the preferred method for comprehensively characterising global transcriptome activity. Unique to cytoreductive surgery (CRS), multiple spatially discrete tumour specimens could be systematically harvested for genomic analysis. To facilitate such downstream analyses, laser capture microdissection (LCM) could be utilized to obtain pure cell populations. The aim of this protocol study was to develop a methodology to obtain high-quality expression data from matched primary tumours and metastases by utilizing LCM to isolate pure cellular populations. We demonstrate an optimized LCM protocol which reproducibly delivered intact RNA used for RNA sequencing and quantitative polymerase chain reaction (qPCR). After pathologic annotation of normal epithelial, tumour and stromal components, LCM coupled with cDNA library generation provided for successful RNA sequencing. To illustrate our framework's potential to identify targets that would otherwise be missed with conventional bulk tumour sequencing, we performed qPCR and immunohistochemical technical validation to show that the genes identified were truly expressed only in certain sub-components. This study suggests that the combination of matched tissue specimens with tissue microdissection and NGS provides a viable platform to unmask hidden biomarkers and provides insight into tumour biology at a higher resolution.


Assuntos
Neoplasias Colorretais/cirurgia , Perfilação da Expressão Gênica/métodos , Tumor de Krukenberg/cirurgia , Microdissecção e Captura a Laser/métodos , Neoplasias Ovarianas/cirurgia , Neoplasias Colorretais/genética , Neoplasias Colorretais/secundário , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Tumor de Krukenberg/genética , Neoplasias Ovarianas/genética , Análise de Sequência de RNA , Manejo de Espécimes , Fluxo de Trabalho
6.
Asia Pac J Clin Oncol ; 16(2): e38-e46, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31693307

RESUMO

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors. METHODS: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm3 ), neutropenia (absolute neutrophils < 2000/mm3 ), and thrombocytopenia (platelets < 140 000/mm3 ). RESULTS: Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression. CONCLUSION: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Doenças Hematológicas/etiologia , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/complicações , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Cuidados Pós-Operatórios , Estudos Retrospectivos , Adulto Jovem
7.
Eur J Surg Oncol ; 44(4): 388-394, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29422251

RESUMO

BACKGROUND: The advent of tyrosine kinase inhibitors as adjuvant therapy has revolutionized the management of GIST and emphasized the need for accurate prognostication systems. Numerous prognostication systems have been proposed for GIST but at present it remains unknown which system is superior. The present systematic review aims to summarize current prognostication systems for primary treatment-naive GIST. METHODS: A literature review of the Pubmed and Embase databases was performed to identify all published articles in English, from the 1st January 2002 to 28th Feb 2017, reporting on clinical prognostication systems of GIST. RESULTS: Twenty-three articles on GIST prognostication systems were included. These systems were classified as categorical systems, which stratify patients into risk groups, or continuous systems, which provide an individualized form of risk assessment. There were 16 categorical systems in total. There were 4 modifications of the National Institute of Health (NIH) system, 2 modifications of Armed Forces Institute of Pathology (AFIP) criteria and 3 modifications of Joensuu (modified NIH) criteria. Of the 7 continuous systems, there were 3 prognostic nomograms, 3 mathematical models and 1 prognostic heat/contour maps. Tumor size, location and mitotic count remain the main variables used in these systems. CONCLUSION: Numerous prognostication systems have been proposed for the risk stratification of GISTs. The most widely used systems today are the NIH, Joensuu modified NIH, AFIP and the Memorial Sloan Kettering Cancer Center nomogram. More validation and comparison studies are required to determine the optimal prognostication system for GIST.


Assuntos
Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/terapia , Nomogramas , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
8.
ANZ J Surg ; 88(11): 1145-1150, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29388353

RESUMO

BACKGROUND: Primary mucosal melanomas (MM) are rare neoplasms arising from melanocytes in mucosal membranes. Delayed diagnosis and aggressive disease biology contribute to a poorer prognosis. The clinical patterns of MMs treated in a large tertiary centre, and the differences between MMs in the head and neck versus other anatomical sites are described. METHODS: A retrospective review of 43 patients diagnosed with MM in the head and neck, urogenital, esophageal and anorectal sites from 1993 to 2015 was conducted. RESULTS: Distribution of head and neck, urogenital and gastrointestinal MM were 42, 30 and 28% respectively. Disease extent was local in 44%, regional in 40% and distal in 12% at diagnosis. Head and neck MMs were more likely to be diagnosed at an earlier stage as compared to other sites (P = 0.04). Surgery was performed with curative intent in 72%, while 2% had palliative surgery for symptom control. Of the remaining patients who did not undergo surgery, four had palliative chemotherapy and/or radiotherapy. Median disease-free survival was 13 months (1-179 months). There was a significantly longer time to locoregional recurrence in head and neck MM (16 months) compared to other sites (11 months) (P = 0.03). The 2-year overall survival was also significantly higher in head and neck MM (P = 0.003). CONCLUSION: MM of the head and neck is diagnosed at an earlier stage and associated with a longer time to locoregional recurrence. Surgical resection is the mainstay of treatment and may offer long-term survival benefit in selected patients.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Melanoma/diagnóstico , Melanoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Mucosa/patologia , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
9.
Asia Pac J Clin Oncol ; 14(2): e193-e202, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28695617

RESUMO

AIM: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is known to improve survival in selected patients with peritoneal metastasis. However, there is limited data supporting the role of CRS and HIPEC in elderly patients (≥65 years old). METHODS: A retrospective review of a prospectively maintained database of patients who underwent CRS-HIPEC between April 2001 and July 2015 from a single institution was performed. Patients were divided into two groups non-elderly (<65 years old), and elderly (≥65 years old). Clinico- pathological parameters, morbidity and overall (OS) and disease-free survival (DFS) of the patients were compared. RESULTS: A total of 177 patients (median age 52, range 9-74) underwent CRS-HIPEC with curative intent. There were 159 non-elderly patients and 18 elderly patients. Median PCI scores were 12 (0-39) for the non- elderly patients and 11 (1-29) for the elderly patients (p=0.77). High-grade complications occurred in 39 non-elderly patients (24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non-elderly patients (38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day (p=0.69). There was no difference in the 30-day mortality between the two groups (0% vs. 0%, p=1). After a median follow-up of 16 months for all patients, there was no difference in 5-years OS (51.0% vs. 59.6%, p=0.88) and 5-years DFS (23.3% vs. 53.3%, p=0.60) between non-elderly and elderly patients. CONCLUSIONS: Surgical outcomes after CRS-HIPEC do not differ significantly between non-elderly and elderly patients. Hence, age should not be a contraindication in selecting patients for CRS and HIPEC.


Assuntos
Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Morbidade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Criança , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
10.
Asian J Surg ; 40(5): 389-395, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27317102

RESUMO

BACKGROUND: In locally advanced pelvic malignancies, there is often involvement of urological organs, necessitating resection and reconstruction, which can be associated with significant complications. METHODS: We retrospectively reviewed 20 patients undergoing urological reconstructions during pelvic oncological surgeries from January 2004 to December 2013. All patients had imaging-proven involvement of at least one urological organ preoperatively. Primary outcome was urological complication rate. Secondary outcomes were nonurological complication, recurrence rate, and overall survival. RESULTS: Median age of presentation was 51 years. Six and 14 patients underwent resections for primary and secondary tumors, respectively. Colorectal tumors were the most common, followed by gynecological cancers. The ureter was the most common urological organ involved, followed by the bladder, prostate, and seminal vesicles. Reconstructive procedures included ileal and sigmoid conduits, ureteroneocystostomies, Boari flap, transureteroureterostomies (TUUs) and direct ureteroureterostomies. Six patients developed major urological complications, requiring endoscopic and surgical reinterventions. The follow-up time was 34 months. Thirteen patients developed recurrence, associated with higher tumor grade and lymphovascular invasion, and occurred at a median time of 10 months. These patients had an overall survival of 20 months, compared to 45 months in patients without recurrence. CONCLUSION: Careful patient selection in pelvic oncological surgeries can significantly prolong survival. Recurrent tumors and greater intraoperative blood loss are associated with higher urological complications. A limited pelvic exenteration and lower radiation doses can reduce complication rates. If higher doses are necessary, conformal techniques and hyperfractionated radiotherapy should be explored. Urological reconstruction should be individualized, according to the extensiveness of urological involvement and exposure of radiation.


Assuntos
Exenteração Pélvica , Neoplasias Pélvicas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Pélvicas/mortalidade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Urológicas/mortalidade
11.
Surg Endosc ; 31(5): 2271-2279, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27631317

RESUMO

BACKGROUND: Laparoscopic wedge resection (LWR) for small gastric gastrointestinal stromal tumors (GIST) is now widely accepted, but its application for large GISTs remains controversial. This study aims to evaluate the feasibility and safety of LWR for suspected large (≥5 cm) gastric GISTs. METHODS: Retrospective review of 82 consecutive patients who underwent attempted LWR for suspected gastric GIST. LWR for large (≥5 cm) (n = 23) tumors was compared with LWR for small (<5 cm) tumors (n = 59). The 23 patients with LWR for large tumors were also compared to 36 consecutive patients who underwent open wedge resection (OWR) for large tumors. RESULTS: Comparison between patients who underwent LWR for large versus small tumors demonstrated that resection of large tumors was associated with a longer operating time. There was no difference in other perioperative outcomes, and oncological outcomes such as frequency of close margins (≤1 mm) and recurrence-free survival. Comparison between patients who underwent LWR versus OWR for large tumors showed that LWR was associated with decreased median time to fluid or solid diet, shorter postoperative stay but longer operating times. There was no difference in oncological outcomes. CONCLUSION: LWR for suspected large gastric GIST is feasible and safe. It is associated with similar short-term outcomes with LWR for small tumors and favorable short-term outcomes over OWR for large tumors without compromising on oncological outcomes.


Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/patologia
12.
Surgery ; 159(4): 1146-56, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26688506

RESUMO

BACKGROUND: Recent studies have demonstrated that the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic for various malignancies; however, there are limited data to date demonstrating their usefulness for gastrointestinal stromal tumors (GISTs). The aim of this study was to determine whether NLR and PLR are prognostic for GIST. METHODS: Three hundred patients who underwent operative resection for primary localized GIST with preoperative results for neutrophil, platelet, and lymphocyte counts available were retrospectively reviewed. Optimal cutoff values for high NLR (≥ 3.0) and PLR (≥ 275) in predicting recurrence-free survival (RFS) were determined. Prognostic factors of RFS were determined using univariate and multivariate Cox regression analyses for the 266 patients who did not receive adjuvant imatinib. RESULTS: On univariate analyses, tumor size, mitotic count, location, and both a high NLR and PLR were significant prognostic indicators of decreased RFS (hazard ratio [HR], 2.89 [95% CI; 1.609-5.179 P < .001] and HR, 3.572 [95% CI, 2.094-6.096; P < .001], respectively). On multivariate analyses, tumor size, mitotic count, tumor location, and both high NLR and PLR were independent prognostic factors of RFS in GIST. Both a high NLR and PLR were significant prognostic factors for GISTs within the National Institutes of Health (NIH) and Armed Forces Institute of Pathology (AFIP) high-risk categories. Addition of NLR or PLR to the NIH or AFIP improved the accuracy of these systems. CONCLUSION: High NLR and PLR were independent prognostic factors of RFS in GIST. NLR and PLR would be useful as a preoperative prognostic tool and its incorporation into current prognostication systems improved their accuracy.


Assuntos
Plaquetas/metabolismo , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Seguimentos , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/sangue , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
13.
World J Surg ; 39(6): 1578-83, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25651962

RESUMO

BACKGROUND: Peritoneal-based malignancy (PBM), especially peritoneal carcinomatosis from gastrointestinal malignancies traditionally carries a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) have been shown to attain long median survival of 34-92 months and 5 year survival of 29-59% in patients with favorable histopathological subtypes. Recurrence after CRS and HIPEC poses a management dilemma. This paper evaluates our institution's experience with repeat CRS and HIPEC, its associated morbidity and outcomes. METHODS: One-hundred and thirty underwent CRS and HIPEC for PBM from April 2001 to June 2013. 49 had peritoneal recurrences, of which 24 had peritoneal only recurrence. 7 out of the 24 underwent a second CRS and HIPEC. RESULTS: Five females and two males with median age of 51 (37-63), underwent a second CRS and HIPEC. The primary malignancies were: 1 peritoneal mesothelioma, 3 appendiceal, 2 ovarian, and 1 colorectal cancers. Median peritoneal cancer indices for the initial and second CRS were 19 and 12, respectively. Completeness of cytoreduction score of 0 was achieved for all patients. Median hospitalization after second CRS and HIPEC was 12 days (7-60). 1 out of 7 (14%) experienced grade 3 or 4 post-operative complications. There was no 30-day or inpatient mortality. Median follow-up was 13 months (1-97). Median disease-free interval between the first CRS and HIPEC to peritoneal recurrence was 20 months (14-87). Median disease-free survival of 6 months (1-97) was achieved after the second CRS and HIPEC. Six patients remained alive without disease and one passed away with disease. Two had recurrences at 12 and 71 months after second CRS and HIPEC, 1 died and the other, still alive, went on to have a third CRS. CONCLUSION: Repeat CRS and HIPEC can achieve prolonged survival in selected patients with peritoneal-based malignancies, and can be performed with acceptable morbidity and mortality.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Apêndice/patologia , Carcinoma/terapia , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/terapia , Adulto , Carcinoma/secundário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Reoperação , Neoplasias Retroperitoneais/cirurgia , Taxa de Sobrevida
14.
Ann Surg Oncol ; 22(11): 3597-605, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25652053

RESUMO

PURPOSE: To validate the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram in a single-institution cohort of patients with gastrointestinal stromal tumors (GISTs), and to compare its predictive accuracy against other established risk classification systems, including the National Institutes of Health (NIH), Armed Forces Institute of Pathology (AFIP), and Joensuu criteria. METHODS: We retrospectively reviewed 289 patients who underwent surgical resection for primary localized GISTs without adjuvant imatinib therapy and compared the actuarial recurrence-free survival (RFS) with the predicted RFS. RESULTS: Tumors >5 cm in size, with high mitotic index, and which had ruptured were significantly associated with recurrent disease. The 2-year RFS was 77.2 % [95 % confidence interval (CI) 71.6-81.8], and the 5-year RFS was 67.9 % (95 % CI 61.7-73.4). The concordance probability of the nomogram of 2-year RFS was 0.71 (SE 0.02), and 5-year RFS was 0.71 (SE 0.19). The 2-year and 5-year MSKCC nomogram probability calculations and the AFIP criteria gave a better estimation of RFS compared to the NIH (p < 0.001) and Joensuu (p < 0.001) criteria. There was no significant difference between the predictive accuracy of the nomogram compared to the AFIP criteria. CONCLUSIONS: The MSKCC nomogram slightly underestimated the probability of RFS after surgical resection of GISTs. It was associated with a significantly better predictive accuracy compared to the NIH and Joensuu. This study suggests that there is a wider than expected prognostic divergence between gastric GISTs versus GISTs arising from the small intestine.


Assuntos
Povo Asiático , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Recidiva Local de Neoplasia/patologia , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Valor Preditivo dos Testes , Probabilidade , Curva ROC , Estudos Retrospectivos , Ruptura Espontânea/complicações , Carga Tumoral
15.
Eur J Surg Oncol ; 40(10): 1263-70, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24947073

RESUMO

UNLABELLED: Patients with clinically palpable lymph node metastases to the groin are treated with groin dissection to control local disease and stage the malignancy. However, the extent of nodal dissection required to optimize survival rate is controversial. AIM: To evaluate the approach to the extent of nodal dissection in advanced lower limb melanomas with clinically palpable inguinal nodes; to review survival outcomes based on the extent of nodal dissection and nodal disease. MATERIALS AND METHODS: A prospectively maintained database of 12 patients with lower limb melanoma was analyzed. Cloquet's node was assessed based on the frozen section result which guided the decision to proceed to iliac-obturator dissection. The correlation of the results of the Cloquet's nodes and radiological imaging to the final histological outcome of groin nodal dissection were compared. RESULTS: The positive predictive value (PPV) of radiological imaging in identifying pelvic nodal disease was 60%. PPV of a positive or indeterminate frozen section result of Cloquet's node was 71.4%. Notably, all patients with a positive frozen section result for the Cloquet's node had positive pelvic nodal disease. Median DFS for all patients is 26 months (range 3-68 months) and the median OS for all patients is 28.5 months (range 5-68 months). Median DFS for node negative patients was 28 months (range 24-68 months). Median DFS for node positive patients was 20 months (range 3-36 months). CONCLUSION: Cloquet's node was shown to be superior to radiological imaging and should be preferentially used to decide on the extent of nodal dissection.


Assuntos
Canal Inguinal , Extremidade Inferior , Excisão de Linfonodo/métodos , Linfonodos/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Virilha , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade , Pelve , Exame Físico , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
16.
Curr Opin Obstet Gynecol ; 26(1): 3-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24247932

RESUMO

PURPOSE OF REVIEW: Ovarian cancer is the commonest gynaecological cancer and the fifth leading cause of cancer death in women worldwide. The majority of patients with ovarian cancer present at an advanced stage, and up to 70% of those treated with a curative approach eventually recur and succumb to their disease. This article examines the management of ovarian cancer over the years and the role of intraperitoneal chemotherapy in the treatment algorithm. RECENT FINDINGS: The surgical paradigm for ovarian cancer has changed and the goal is optimal cytoreduction with no residual disease. Intraperitoneal chemotherapy has been found to be superior to intravenous treatment alone, and the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has produced encouraging results with improved disease-free and overall survivals at acceptable morbidity and mortality rates. SUMMARY: The most important prognostic factor for ovarian cancer survival is the ability to achieve optimal cytoreduction with no residual disease. CRS and HIPEC should be considered as an option for the management of advanced ovarian cancer and further trials are required to determine its role in both the primary and recurrent settings.


Assuntos
Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Fatores Etários , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
17.
Ann Acad Med Singap ; 42(6): 291-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23842770

RESUMO

INTRODUCTION: Peritoneal mesothelioma is a rare neoplasm. Due to the limited understanding of its biology and behaviour, peritoneal mesothelioma poses a diagnostic and management challenge. The management of peritoneal mesothelioma has been controversial; systemic chemotherapy, palliative surgery and cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) have been described. MATERIALS AND METHODS: This study shares our experience with cytoreductive surgery and HIPEC for 5 out of the 6 cases of peritoneal mesotheliomas treated surgically, at a single institution in Singapore over the past 2 years. Computed tomography (CT) scans, positron emission tomography (PET)-CT scans and tumour markers were performed preoperatively but were not conclusive for the disease. All 6 cases presented to the Department of Surgical Oncology at National Cancer Centre Singapore, were diagnosed by histology of intraoperative biopsies. The combination of aggressive cytoreductive surgery and HIPEC was performed in 5 patients, with abandonment of procedure in 1 with extensive disease, who was treated with systemic chemotherapy instead. RESULTS: Median duration of surgery, median length of hospital stay, and median follow-up duration were 7.04 hours, 11 days, and 15 months respectively. One postoperative morbidity relating to chemical peritonitis required exploratory laparotomy with good outcome. There were no mortality. All patients are alive at the last follow-up with no evidence of recurrences at 4 to 31 months from the time of their surgery. CONCLUSION: Peritoneal mesothelioma is a rare disease that requires early diagnosis and can be effectively treated by CRS and HIPEC in selected group of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/métodos , Criocirurgia/métodos , Hipertermia Induzida/métodos , Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
18.
Jpn J Clin Oncol ; 43(3): 219-24, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23303840

RESUMO

Cancer is the leading cause of mortality in Singapore. The age-standardized incidence rates continue to increase as the population grows and ages, and the influence of environmental and lifestyle choices bear their consequences. The increase is most marked in colorectal, breast and prostate cancers, mirroring the most common cancers seen in other developed countries. The eradication of infectious disease such as hepatitis B, through the implementation of the hepatitis B immunization programme in 1985, has led to the decline in liver cancer. The Singapore Cancer Registry collates detailed information on newly diagnosed and existing cancer cases, enabling the study and understanding of cancer trends in the population and across the different ethnic groups. A coordinated approach to address cancer prevention and treatment through public education and increased awareness, screening and early detection, and the institution of appropriate multidisciplinary care, on a background of continued basic and clinical research is required to deliver quality cancer care.


Assuntos
Neoplasias/epidemiologia , Distribuição por Idade , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Etnicidade , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Neoplasias/etnologia , Neoplasias/terapia , Assistência ao Paciente/tendências , Neoplasias da Próstata/epidemiologia , Singapura/epidemiologia
19.
World J Surg Oncol ; 10: 91, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22613459

RESUMO

This is a case of metastatic lung cancer of the lymphoepithelial-like carcinoma (LELC) variant who first presented with symptomatic brain metastasis. The patient underwent local and systemic treatment for metastatic disease with good clinical outcome. The patient was disease free for four years then she had primary lung recurrence which was surgically resected. She underwent a second course of chemotherapy with saw her through another two years of disease free period. A recurrence of the cancer was detected intra-abdominally on the seventh year of diagnosis. This was treated again with surgical resection and another course of chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Tecido Linfoide/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Doença Crônica , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Prognóstico
20.
Am J Surg ; 194(3): 390-1, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17693288

RESUMO

Bochdalek hernia is a type of congenital diaphragmatic hernia that typically presents in childhood, but may rarely be detected in adults. The treatment of choice is operative repair due to the risk of visceral herniation and strangulation.


Assuntos
Hérnia Diafragmática , Adulto , Hérnia Diafragmática/diagnóstico , Hérnia Diafragmática/cirurgia , Humanos , Masculino
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