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1.
Mod Pathol ; 37(8): 100535, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852812

RESUMO

The DESTINY Breast-04 trial revealed survival advantages of trastuzumab deruxtecan for women with metastatic HER2-low breast cancer (1+ or 2+ immunohistochemistry [IHC], without amplification). Although this trial applied the 2018 Americal Society of Clinial Oncology (ASCO)/College of American Pathologists (CAP) HER2 IHC scoring criteria, the subjectivity and imprecision in IHC scoring have raised concerns that patients' treatment may be misaligned. Our group of 9 experienced breast pathologists collated a deidentified set of 60 breast cancer core biopsies from 3 laboratories, evaluated with the Ventana 4B5 HER2 assay and mostly scored locally as HER2 0 or 1+. Based on ASCO/CAP 2018 criteria and our extensive experience of reporting HER2 IHC, we specified scoring conventions for cancers with low levels of HER2 protein expression, articulating specific scoring pitfalls. Each pathologist then reviewed digitized whole slide images of the IHC slides and scored the HER2 expression for each case. At a subsequent consensus workshop, we reviewed the cases jointly to establish consensus scores for each case and determine the percentage of HER2 expressing tumor cells. Consensus was reached on all cases, with 40 classified as 1+ and 3 as 2+ (not amplified), totaling 43 (71.7%) HER2-low cancers. The remaining cases were HER2 0. In 93.3% of cases (56/60), the consensus score matched with the majority opinion of pathologists' independent scores. Seven (41.2%) of the 17 cases reported locally as HER2 0 were classified as HER2 low. Conversely, among 32 cases with local scores of 1+, 7 (21.8%) were reclassified as ultralow or null. Individual pathologists' accuracy in matching the consensus scores ranged from 73.3% to 91.67% (mean, 80.74%). Among HER2-low cancers those in which <20% of the tumor cells expressed HER2 had the lowest concordance levels. Observers Cohen's κ coefficients for concordance were excellent for 4, good in 1, and moderate in the 4 observers. This reference set of cases with expert consensus HER2 scores will be invaluable for peer training and development of our national external quality assurance program for HER2-low cancers. For assessing breast cancers at the low end of HER2 protein expression, our targeted scoring criteria and explicit instruction on pitfalls improved pathologists' accuracy and concordance.

2.
Intern Med J ; 53(8): 1390-1399, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35675149

RESUMO

BACKGROUND: Computed tomography-guided transthoracic biopsy (CT-TTB) is the 'gold standard' biopsy for lung nodules. Radial-endobronchial ultrasound (R-EBUS) bronchoscopy is another recommended biopsy but carries a lower diagnostic yield. Addition of cryobiopsy with R-EBUS (Cryo-Radial) has shown promising results. There are no studies comparing CT-TTB with Cryo-Radial biopsy. AIM: The co-primary aims were the diagnostic yeild and safety. The secondary aim: ability to test epidermal growth factor receptor (EGFR). METHODS: A randomised controlled, multicentre exploratory study was conducted at three tertiary hospitals. Patients with nodules >1 cm on CT of the chest were randomised to CT-TTB or Cryo-Radial. With Cryo-Radial, patients had 1-3 cryo-biopsies in addition to at least one R-EBUS biopsy through the 2.6 mm guide sheath. RESULTS: Forty-eight patients were randomised: 22 to CT-TTB and 26 to Cryo-Radial. Sixteen in the CT-TTB and 20 in the Cryo-Radial received the allocated biopsy. The diagnostic yield was CT-TTB 93.8% (15/16) versus Cryo-Radial 85% (17/20) P = 0.61 and the odds ratio was 0.37. For 5/13 (38%), a diagnosis was solely made on cryobiopsy. Eleven (78%) of 14 in CT-TTB versus 7/10 (70%) Cryo-Radial were suitable for EGFR testing P = 0.66, with odds ratio 0.63. Pneumothorax occurrence was 44% (7/16) in CT-TTB versus 4.2% (1/24) in Cryo-Radial. Two (12.5%) of 16 CT-TTB required chest drain insertion. CONCLUSION: Cryo-Radial is comparable in diagnostic yield and ability to perform EGFR testing with a significantly lower risk of pneumothorax, compared with CT-TTB. Cryo-Radial has the additional advantage of mediastinal staging during the same procedure with Linear-EBUS and is a promising first-line tool in the diagnostic method of lung cancer.


Assuntos
Neoplasias Pulmonares , Pneumotórax , Humanos , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Biópsia/efeitos adversos , Biópsia/métodos , Tomografia Computadorizada por Raios X/métodos , Endossonografia/métodos , Broncoscopia/efeitos adversos , Broncoscopia/métodos
3.
Gut ; 71(5): 864-870, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34172512

RESUMO

OBJECTIVE: Endoscopic mucosal resection (EMR) in the colon has been widely adopted, but there is limited data on the histopathological effects of the differing electrosurgical currents (ESCs) used. We used an in vivo porcine model to compare the tissue effects of ESCs for snare resection and adjuvant margin ablation techniques. DESIGN: Standardised EMR was performed by a single endoscopist in 12 pigs. Two intersecting 15 mm snare resections were performed. Resections were randomised 1:1 using either a microprocessor-controlled current (MCC) or low-power coagulating current (LPCC). The lateral margins of each defect were treated with either argon plasma coagulation (APC) or snare tip soft coagulation (STSC). Colons were surgically removed at 72 hours. Two specialist pathologists blinded to the intervention assessed the specimens. RESULTS: 88 defects were analysed (median 7 per pig, median defect size 29×17 mm). For snare ESC effects, 156 tissue sections were assessed. LPCC was comparable to MCC for deep involvement of the colon wall. For margin ablation, 172 tissue sections were assessed. APC was comparable to STSC for deep involvement of the colon wall. Islands of preserved mucosa at the coagulated margin were more likely with APC compared with STSC (16% vs 5%, p=0.010). CONCLUSION: For snare resection, MCC and LPCC did not produce significantly different tissue effects. The submucosal injectate may protect the underlying tissue, and technique may more strongly dictate the depth and extent of final injury. For margin ablation, APC was less uniform and complete compared with STSC.


Assuntos
Pólipos do Colo , Ressecção Endoscópica de Mucosa , Animais , Colo/patologia , Colo/cirurgia , Pólipos do Colo/patologia , Colonoscopia/métodos , Eletrocirurgia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Suínos
4.
Breast Cancer Res Treat ; 188(3): 729-737, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33751322

RESUMO

PURPOSE: This study aimed to determine the interobserver concordance of two methods for proliferation assessment in breast cancer using Ki67 immunohistochemistry. METHODS: Ki67 was independently assessed in randomly selected tumour samples from patients with lymph node-negative breast cancer using two different methods: either cell counting or visual estimation of hot spot areas. For hot spot cell counting, positive and negative cell numbers were recorded for total cell counts of 300-500, 500-800 and 800-1000 cells. Visual estimation involved allocation of a score from 1 to 5 using a visual scale to estimate percentage positivity. Interobserver agreement for hot spot counting was calculated using a two-way fixed effects intraclass correlation model, and by using Cohen's kappa measure for visual assessment. Prognostic concordance between the two methods was also calculated using Cohen's kappa. RESULTS: Samples from 96 patients were included in this analysis. Interobserver agreement for hot spot cell counting was excellent (> 0.75) across all three cell count ranges, with correlation coefficients of 0.88 (95% CI 0.84-0.92), 0.87 (95% CI 0.82-0.91) and 0.89 (95% CI 0.85-0.92), respectively. Interobserver agreement with visual estimation was greatest for hot spots compared with areas of intermediate or low proliferation, with kappa scores of 0.49, 0.42 and 0.40, respectively. Both assessment methods demonstrated excellent prognostic agreement. CONCLUSIONS: Interobserver and prognostic concordance in Ki67 immunohistochemistry assessments was high using either hot spot cell counting or visual estimation, further supporting the utility and reproducibility of these cost-efficient methods to assess proliferation.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67 , Variações Dependentes do Observador , Reprodutibilidade dos Testes
5.
Gastrointest Endosc ; 90(3): 467-479.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31077699

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is an effective, minimally invasive, surgery-sparing technique for the treatment of early gastric cancer (EGC). It is not well established whether EGC within the Japanese expanded criteria can be safely and effectively treated using ESD in the West. We describe the outcomes of ESD for endoscopically suspected, biopsy specimen-confirmed EGC and its adenomatous precursor lesions (pEGC) using the Vienna classification of dysplasia in a Western cohort. METHODS: Prospective data were collected on all pEGCs undergoing ESD at a single expert endoscopy center. Outcomes were compared among pEGC, satisfying the Japanese absolute and expanded criteria, those outside criteria, and those specimens that contained low-grade dysplasia (LGD) only. Specialist GI pathologists reviewed and classified all ESD specimens. Patients were followed up at 6 and 12 months. RESULTS: Over 71 months, 135 pEGCs in 121 patients (mean age, 72.0 years; 61.2% men) underwent ESD. Median pEGC size was 20 mm (interquartile range, 15-30), and 62 (45.9%) satisfied the expanded clinical criteria. Perforation occurred in 1.5% and postprocedural bleeding in 5.2%. Forty-two pEGCs (31.1%) contained LGD only. Rates of en bloc and R0 resection were 94.8% and 86.7%, respectively. One hundred seven pEGCs (79.2%) met the absolute or expanded criteria for endoscopic cure. Two pEGCs recurred during follow-up. Ten of 26 patients with pEGC (38.5%) outside criteria for cure underwent surgery after ESD with residual tumor detected in 3 specimens. Fifteen patients with outside criteria for pEGCs did not undergo surgery because of frailty or their expressed wish. Eleven of 15 patients have so far undergone first surveillance with 1 of 11 experiencing endoscopic and histologic recurrence. CONCLUSIONS: ESD is a safe and effective treatment for pEGCs in a Western context. Patients who either decline or are too frail for surgery, with outside criteria resections, may benefit from ESD for local disease control. Large Western studies of ESD for pEGCs are required to define long-term patient outcomes and surveillance guidelines, particularly where pathology shows LGD or high-grade dysplasia only. (Clinical trial registration number: NCT02306707.).


Assuntos
Adenocarcinoma/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Mucosa Gástrica/cirurgia , Lesões Pré-Cancerosas/cirurgia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Austrália , Feminino , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Neoplasias Gástricas/patologia , População Branca
6.
Gut ; 67(11): 1965-1973, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-28988198

RESUMO

OBJECTIVE: To compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm. DESIGN: An incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed. RESULTS: 1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US$210 112. U-ESD was only cost-effective among higher risk rectal lesions. CONCLUSION: S-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs. TRIAL REGISTRATION NUMBER: NCT02000141.


Assuntos
Colonoscopia/economia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adulto , Colo/patologia , Colo/cirurgia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/economia , Neoplasias Colorretais/patologia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/estatística & dados numéricos , Feminino , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Masculino , Prevalência , Estudos Prospectivos , Reto/patologia , Reto/cirurgia , Sensibilidade e Especificidade , Resultado do Tratamento
7.
Gastroenterology ; 153(3): 732-742.e1, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28583826

RESUMO

BACKGROUND & AIMS: Among patients with large colorectal sessile polyps or laterally spreading lesions, it is important to identify those at risk for submucosal invasive cancer (SMIC). Lesions with overt endoscopic evidence of SMIC are referred for surgery, although those without these features might still contain SMIC that is not visible on endoscopic inspection (covert SMIC). Lesions with a high covert SMIC risk might be better suited for endoscopic submucosal dissection than for endoscopic mucosal resection (EMR). We analyzed a group of patients with large colon lesions to identify factors associated with SMIC, and examined lesions without overt endoscopic high-risk signs to determine factors associated with covert SMIC. METHODS: We performed a prospective cohort study of consecutive patients referred for EMR of large sessile or flat colorectal polyps or laterally spreading lesions (≥20 mm) at academic hospitals in Australia from September 2008 through September 2016. We collected data on patient and lesion characteristics, outcomes of procedures, and histology findings. We excluded serrated lesions from the analysis of covert SMIC due to their distinct phenotype and biologic features. RESULTS: We analyzed 2277 lesions (mean size, 36.9 mm) from 2106 patients (mean age, 67.7 years; 53.2% male). SMIC was evident in 171 lesions (7.6%). Factors associated with SMIC included Kudo pit pattern V, a depressed component (0-IIc), rectosigmoid location, 0-Is or 0-IIa+Is Paris classification, non-granular surface morphology, and increasing size. After exclusion of lesions that were obviously SMIC or serrated, factors associated with covert SMIC were rectosigmoid location (odds ratio, 1.87; P = .01), combined Paris classification, surface morphology (odds ratios, 3.96-22.5), and increasing size (odds ratio, 1.16/10 mm; P = .012). CONCLUSIONS: In a prospective study of 2106 patients who underwent EMR for large sessile or flat colorectal polyps or laterally spreading lesions, we associated rectosigmoid location, combined Paris classification and surface morphology, and increasing size with increased risk for covert malignancy. Rectosigmoid 0-Is and 0-IIa+Is non-granular lesions have a high risk for malignancy, whereas proximally located 0-Is or 0-IIa granular lesions have a low risk. These findings can be used to inform decisions on which patients should undergo endoscopic submucosal dissection, EMR, or surgery. ClinicalTrials.gov, Number: NCT02000141.


Assuntos
Neoplasias do Colo/patologia , Pólipos do Colo/classificação , Pólipos do Colo/patologia , Ressecção Endoscópica de Mucosa , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo Sigmoide/patologia , Pólipos do Colo/cirurgia , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Reto/patologia , Medição de Risco , Fatores de Risco , Adulto Jovem
8.
Gastrointest Endosc ; 87(1): 222-231.e2, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28713060

RESUMO

BACKGROUND AND AIMS: Dysplasia within sessile serrated polyps (SSPs) is difficult to detect and may be mistaken for an adenoma, risking incomplete resection of the background serrated tissue, and is strongly implicated in interval cancer after colonoscopy. The use of endoscopic imaging to detect dysplasia within SSPs has not been systematically studied. METHODS: Consecutively detected SSPs ≥8 mm in size were evaluated by using a standardized imaging protocol at a tertiary-care endoscopy center over 3 years. Lesions suspected as SSPs were analyzed with high-definition white light then narrow-band imaging. A demarcated area with a neoplastic pit pattern (Kudo type III/IV, NICE type II) was sought among the serrated tissue. If this was detected, the lesion was labeled dysplastic (sessile serrated polyp with dysplasia); if not, it was labeled non-dysplastic (sessile serrated polyp without dysplasia). Histopathology was reviewed by 2 blinded specialist GI pathologists. RESULTS: A total of 141 SSPs were assessed in 83 patients. Median lesion size was 15.0 mm (interquartile range 10-20), and 54.6% were in the right side of the colon. Endoscopic evidence of dysplasia was detected in 36 of 141 (25.5%) SSPs; of these, 5 of 36 (13.9%) lacked dysplasia at histopathology. Two of 105 (1.9%) endoscopically designated non-dysplastic SSPs had dysplasia at histopathology. Endoscopic imaging, therefore, had an accuracy of 95.0% (95% confidence interval [CI], 90.1%-97.6%) and a negative predictive value of 98.1% (95% CI, 92.6%-99.7%) for detection of dysplasia within SSPs. CONCLUSIONS: Dysplasia within SSPs can be detected accurately by using a simple, broadly applicable endoscopic imaging protocol that allows complete resection. Independent validation of this protocol and its dissemination to the wider endoscopic community may have a significant impact on rates of interval cancer. (Clinical trial registration number: NCT03100552.).


Assuntos
Adenoma/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Adenoma/patologia , Adenoma/cirurgia , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita , Carga Tumoral
9.
Endoscopy ; 50(11): 1080-1088, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29739023

RESUMO

BACKGROUND: Sessile serrated polyps (SSPs) are important precursors of colorectal carcinoma and interval cancer. Large SSPs (≥ 20 mm) outside the definition of serrated polyposis syndrome (SPS) have not been studied in comparison with SPS. We aimed to describe the characteristics of patients with large SSPs in this context. METHODS: Patients with at least one SSP (≥ 20 mm) were eligible. Data from three consecutive colonoscopies were used to compare clinical and endoscopic characteristics in three patient groups: SPS, a solitary large SSP, and patients with at least two SSPs without fulfilling the criteria for SPS (oligo-SSP). Data on the diagnostic colonoscopy were collected retrospectively, whereas the remaining data was collected prospectively. RESULTS: 67/146 patients (45.9 %) had SPS, 53/146 (36.3 %) had a solitary SSP, and 26/146 (17.8 %) were categorized as oligo-SSP. Personal (16.4 %, 9.4 %, and 11.5 %, respectively) and family (17.9 %, 17.0 %, and 23.1 %, respectively) history of colorectal carcinoma did not differ significantly between groups. Polyp burden was greater in SPS compared with solitary SSP but was not different from oligo-SSP (advanced adenomas: SPS 32.8 % vs. solitary SSP 9.4 % [P = 0.002] vs. oligo-SSP 34.6 % [P = 0.87]; ≥ 10 conventional adenomas: 11.9 % vs. 0 % [P = 0.01] vs. 3.8 % [P = 0.44], respectively). Dysplasia in large SSPs was frequent in all groups (41.1 % overall). SPS was recognized by referring endoscopists in only 9.0 % of cases. CONCLUSION: Patients with oligo-SSPs have similar synchronous polyp burden and clinical characteristics as patients with SPS and may require similar surveillance. Modification of the criteria for the diagnosis of SPS to include this group seems warranted. Patients with a solitary SSP have a lower risk of synchronous polyps, including advanced adenomas. Larger studies are warranted to determine whether these patients may return to standard surveillance following complete examination and clearance of the colon.


Assuntos
Polipose Adenomatosa do Colo/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Lesões Pré-Cancerosas/patologia , Polipose Adenomatosa do Colo/diagnóstico por imagem , Idoso , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Estudos Prospectivos , Estudos Retrospectivos
10.
Gut ; 66(4): 644-653, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26786685

RESUMO

OBJECTIVE: Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. DESIGN: Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. RESULTS: From a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p<0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p<0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20-25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups. CONCLUSION: Recurrence after EMR of 20-25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01368289.


Assuntos
Adenoma/cirurgia , Perda Sanguínea Cirúrgica , Pólipos do Colo/cirurgia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa , Perfuração Intestinal/etiologia , Recidiva Local de Neoplasia/patologia , Hemorragia Pós-Operatória/etiologia , Adenoma/patologia , Assistência ao Convalescente , Fatores Etários , Idoso , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Prospectivos , Falha de Tratamento , Carga Tumoral
11.
Endoscopy ; 48(2): 117-22, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26535562

RESUMO

BACKGROUND AND STUDY AIMS: Stricture formation is the main limitation of endoscopic resection in the esophagus. The optimal electrosurgical current (ESC) for endoscopic resection in the esophagus and other gastrointestinal sites is unknown. There may be a relationship between the type of ESC used and the development of post-procedure esophageal stricture. Unlike the low power coagulating current (LPCC), the microprocessor-controlled current (MCC), which alternates between short pulse cutting and coagulation, avoids high peak voltages that are thought to result in deep thermal injury. The aim of this study was to determine the histopathological variables associated with these two commonly employed ESCs used for esophageal endoscopic resection. METHODS: Standardized endoscopic resection of normal mucosa by band mucosectomy was performed by a single endoscopist in 12 adult pigs. The procedures were randomized 1 : 1 to either LPCC (ERBE 100 C at 25 W) or MCC (ERBE Endocut Q, Effect 3). Necropsy and esophagectomy were performed at 72 hours after the procedure. Two histopathologists, who were blinded to the ESC allocation, independently assessed the presence and depth of ulceration, necrosis and inflammation. RESULTS: A total of 45 resections were analyzed. In the LPCC and MCC groups, ulceration extending into the muscularis propria was present in 9/24 (37.5 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.04). Necrosis extending into the muscularis propria was present in 13/24 (54.1 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.002). One case of microperforation with muscularis propria injury was noted in the LPCC group compared with none in the MCC group. The quantified mean depth of ulceration, necrosis, and acute inflammation was significantly greater in the LPCC group.  CONCLUSIONS: In an in vivo porcine survival model of esophageal endoscopic mucosal resection, the use of MCC resulted in significantly less deep thermal ulceration, necrosis, and acute inflammation compared with LPCC. MCC should be used in preference over LPCC for esophageal endoscopic resection.


Assuntos
Esôfago de Barrett/cirurgia , Eletrocirurgia/métodos , Esofagectomia/métodos , Esofagoscopia/métodos , Esôfago/patologia , Mucosa Intestinal/cirurgia , Neoplasias Experimentais , Animais , Esôfago de Barrett/patologia , Estenose Esofágica/prevenção & controle , Esôfago/cirurgia , Mucosa Intestinal/patologia , Suínos
13.
Research (Wash D C) ; 7: 0382, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812532

RESUMO

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

14.
Methods Protoc ; 6(2)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37104017

RESUMO

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

15.
Cell Rep Med ; 4(11): 101257, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37918406

RESUMO

The definitive diagnosis of non-alcoholic steatohepatitis (NASH) currently relies on invasive and labor-intensive liver biopsy. Here, we identified soluble CUB domain-containing protein 1 (sCDCP1) as a top-ranked non-invasive biomarker for NASH using Olink-based proteomics in 238 obese individuals with liver biopsies. Both the circulating concentration and hepatic mRNA abundance of sCDCP1 were significantly elevated in patients with NASH and correlated closely with each histological feature of NASH. In the pooled multicenter validation cohort, sCDCP1 as a standalone biomarker achieved an area under the receiver operating characteristic (AUROC) of 0.838 (95% confidence interval [CI] 0.789-0.887) for diagnosing NASH, which is better than those achieved with cytokeratin-18 and other non-invasive tests. Furthermore, the C-DAG model established by the combination of sCDCP1 with diabetes, aspartate aminotransferase (AST), and gender accurately rules in and rules out both NASH and fibrotic NASH (gray zones <20%). Thus, sCDCP1-based non-invasive tests can be potentially implemented for screening and early diagnosis of NASH and for ruling out low-risk individuals to avoid unnecessary liver biopsies.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , População do Leste Asiático , Obesidade/diagnóstico , Biomarcadores , Medição de Risco , Antígenos de Neoplasias , Moléculas de Adesão Celular
16.
Respirol Case Rep ; 10(5): e0935, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35386575

RESUMO

Radial EndoBronchial UltraSound (R-EBUS)-guided biopsies are a promising biopsy technique for pulmonary nodules suspected of lung cancer with great safety profile. Programmed cell death ligand 1 (PD-L1) testing is increasingly demanded from lung biopsies. GenCut is a novel blunt tool that can be used to obtain core biopsies. This case series explores prospective performance of the GenCut core biopsy with R-EBUS. Once Peripheral Pulmonary Lesion was located, GenCut biopsy was performed followed by conventional (forceps ± cytology brush) R-EBUS biopsies. The overall diagnostic yield for the 16 patients with a mean peripheral pulmonary lesion (PPL) size of 4.1 cm was 100% from multi-modal R-EBUS sampling. The diagnostic yield for GenCut tool alone was 13/16 (81.2%) and the ability to perform PD-L1 from GenCut was 10/16 (62.5%). There were no adverse events recorded. GenCut tool is a novel blunt instrument that can be used safely to obtain a core biopsy suitable for PD-L1 in combination with R-EBUS without compromising the high safety profile.

17.
J Clin Endocrinol Metab ; 107(8): e3230-e3240, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35532410

RESUMO

CONTEXT: Metabolic associated fatty liver disease (MAFLD) is the hepatic manifestation of obesity-related metabolic syndrome (MetS). Noninvasive biomarkers for monitoring the progression and severity of these metabolic comorbidities are needed. OBJECTIVES: To investigate the associations of serum thrombospondin-2 (TSP2) with MetS and MAFLD severity, and the potential diagnostic value of serum TSP2 for identifying at-risk metabolic associated steatohepatitis (MASH). METHODS: Blood samples, clinical data, and liver biopsies were collected from consecutively recruited 252 individuals with morbid obesity receiving bariatric surgery. Histopathology samples of liver biopsies were examined in a blinded fashion by 3 independent pathologists. Serum TSP2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum TSP2 levels were significantly elevated in MetS (1.58 [1.07-2.20] ng/mL) compared with non-MetS (1.28 [0.84-1.73] ng/mL; P = .006) in obese patients and positively correlated with increasing number of the MetS components, fasting glucose, glycated hemoglobin, fasting insulin, C-peptide, and homeostatic model assessment of insulin resistance after adjustment of conventional confounders. Serum TSP2 levels differentiated MASH (1.74 [1.32-3.09] ng/mL) from the other non-MASH less severe groups: normal liver (1.41 [1.04-1.63] ng/mL), simple steatosis (1.45 [0.89-1.92] ng/mL), and borderline MASH (1.30 [0.99-2.17] ng/mL) (P < .05). Elevated serum TSP2 was positively associated with the severity of hepatic steatosis, inflammation, fibrosis, and abnormal liver function independent of age, sex and adiposity. Furthermore, high serum TSP2 identified at-risk MASH with area under the operating curve of 0.84 (95% CI 0.70-0.98). CONCLUSION: Serum TSP2 is closely associated with severity and progression of MetS and MAFLD, and is a promising noninvasive biomarker for differentiating MASH from benign steatosis and identifying at-risk MASH patients among individuals with obesity.


Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Trombospondinas , Biomarcadores/sangue , Índice de Massa Corporal , Humanos , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Índice de Gravidade de Doença , Trombospondinas/sangue
18.
Cancer Rep (Hoboken) ; 4(1): e1297, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33030308

RESUMO

BACKGROUND: There is significant variation in attitude both towards the role of microsatellite instability (MSI) in predicting prognosis, and towards its role in guiding which Stage II colon cancer patients may benefit from adjuvant chemotherapy. AIM: To examine the current status of specialist attitudes towards MSI in guiding prognosis and adjuvant therapy in stage II colon cancer. METHODS: The Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. A 5-scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP). RESULTS: 164 specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. 80.5% regularly attended colorectal multidisciplinary team (MDT) meetings. 89.63% and 59.26% of specialists reported that MSI status was likely or definitely to influence prognosis in colon cancer and recommendations for adjuvant therapy in Stage II colon cancer respectively. IRT modelling was achieved in 17 pathological features for prognosis. MSI IRT score was 4.47 (95% CI: 4.05-4.68). IRT modelling was achieved in 10 pathological features for adjuvant therapy. MSI IRT score was 3.62 (2.89-4.15). MSI ranked 10 (of 17) in order of importance in determining prognosis and ranked three (of 10) in guiding adjuvant therapy. CONCLUSION: MSI status is considered an important biomarker when selecting patients for adjuvant therapy in Stage II colon cancer. MSI is also considered useful in prognostication of colon cancer. MSI status was ranked similar to the tumour grade of differentiation and the presence of perineural invasion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colectomia/estatística & dados numéricos , Neoplasias do Colo/terapia , Instabilidade de Microssatélites , Padrões de Prática Médica/estatística & dados numéricos , Australásia/epidemiologia , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Tomada de Decisão Clínica/métodos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Estudos de Viabilidade , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Oncologistas/estatística & dados numéricos , Patologistas/estatística & dados numéricos , Prognóstico , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos
19.
J Surg Case Rep ; 2021(9): rjab396, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34567515

RESUMO

Granular cell tumours (GCTs) are generally benign neoplasms, which are believed to be of neural origin. They are uncommon in the gastrointestinal tract. They are rarely found in the colon and even more rarely found to be multiple. We present a case of a man who underwent a right hemicolectomy for a submucosal lesion and polyps and was found to have multiple nodules diagnosed as caecal GCTs with cellular atypia. While uncommon, this case shows it remains an important differential due to implications for patient management, given the often benign nature of disease.

20.
World J Clin Oncol ; 12(4): 238-248, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33959477

RESUMO

BACKGROUND: Recent studies in non-colorectal malignancy have associated T resident memory (TRM) cells with improved patient survival. It is unknown if TRM plays a role in colorectal cancer (CRC). AIM: To examine the potential role of TRM cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status. METHODS: Patients with known MSI and BRAF mutation status were eligible for inclusion in this study. CRC tumour sections stained with haematoxylin and eosin were microscopically reviewed and the images scanned prior to assessment for location of invading edge and core of tumour. Sequential sections were prepared for quantitative multiplex immunohistochemistry (IHC) staining. Opal Multiplex IHC staining was performed with appropriate positive and negative controls and imaged using a standard fluorescent microscope fitted with a spectral scanning camera (Mantra) in conjunction with Mantra snap software. Images were unmixed and annotated in inForm 2.2.0. Statistical analysis was performed using Graphpad Prism Version 7 and Stata Version 15. RESULTS: Seventy-two patients with known MSI and BRAF status were included in the study. All patients were assessed for MSI by IHC and high resolution capillary electrophoresis testing and 44 of these patients successfully underwent quantitative multiplex IHC staining. Overall, there was a statistically significant increase in CD8+ TRM cells in the MSI (BRAF mutant and wild type) group over the microsatellite stable (MSS) group. There was a statistically significant difference in CD8+ TRM between high level MSI (MSI-H):BRAF mutant [22.57, 95% confidence interval (CI): 14.31-30.84] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0076 andMSI-H:BRAF wild type [16.18 (95%CI: 10.44-21.93)] vs MSS [8.031 (95%CI: 4.698-11.36)], P = 0.0279. There was no statistically significant difference in CD8 T cells (both CD8+CD103- and CD8+CD103+TRM) between MSI-H: BRAF mutant and wild type CRC. CONCLUSION: This study has shown that CD8+ TRM are found in greater abundance in MSI-H CRC, both BRAF mutant and MSI-H:BRAF wild type, when compared with their MSS counterpart. CD8+ TRM may play a role in the immunogenicity in MSI-H CRC (BRAF mutant and BRAF wild type). Further studies should focus on the potential immunogenic qualities of TRM cells and investigate potential immunotherapeutic approaches to improve treatment and survival associated with CRC.

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