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PURPOSE: Patients with chemotherapy-responsive advanced biliary tract cancers (BTCs) are usually observed after 6 months of gemcitabine-based therapy. There is limited prospective evidence for maintenance strategies after chemotherapy. METHODS: This investigator-initiated, open-label, randomized, integrated phase II-III study enrolled adult patients with advanced BTC from two cancer centers in India. Patients with histologically confirmed advanced biliary tract adenocarcinoma who had at least disease stabilization after 6 months of gemcitabine-based chemotherapy were randomly assigned (1:1) to either active surveillance or switch maintenance, which was a combination of bevacizumab 5 mg/kg intravenous once every 21 days plus erlotinib 100 mg once daily. Both arms were continued until disease progression, unacceptable toxicity, or patient decision to withdraw. The primary end point of the phase II component of the trial was investigator-evaluated progression-free survival. This trial is registered with Clinical Trials Registry of India (CTRI/2019/05/019323I). RESULTS: From May 2021 to November 2022, 98 patients were randomly assigned to active surveillance (n = 49) or bevacizumab-erlotinib (n = 49). A majority of patients had gallbladder cancer (80%). The median follow-up was 13.4 months. The median progression-free survival was 3.1 months (95% CI, 2.47 to 3.64) in the active surveillance group versus 5.3 months (95% CI, 3.53 to 7.04) in the bevacizumab-erlotinib group (hazard ratio, 0.51 [95% CI, 0.33 to 0·74]; P = .0013). The most common grade 3 class-specific adverse events associated with bevacizumab-erlotinib were acneiform rash 1 (2%) and oral stomatitis 1 (2%) with erlotinib and bleeding 1 (2%) with bevacizumab. CONCLUSION: The combination of bevacizumab and erlotinib as switch maintenance improves progression-free survival with an acceptable safety profile compared with active surveillance in patients with advanced BTCs in this phase II study. The trial moves on to the phase III component to evaluate improvement in overall survival.
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BACKGROUND: We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). METHODS: This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. RESULTS: Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. CONCLUSION: FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944).
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Docetaxel , Junção Esofagogástrica , Fluoruracila , Leucovorina , Oxaliplatina , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Pessoa de Meia-Idade , Feminino , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Docetaxel/administração & dosagem , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Idoso , Receptor ErbB-2/genética , Oxaliplatina/administração & dosagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Estimativa de Kaplan-Meier , Compostos Organoplatínicos/administração & dosagem , Instabilidade de Microssatélites , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologiaRESUMO
Importance: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs). Objective: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT). Design, Setting, and Participants: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023. Interventions: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity. Results: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm. Conclusions and Relevance: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs. Trial Registration: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Cisplatino , Desoxicitidina , Neoplasias da Vesícula Biliar , Gencitabina , Humanos , Neoplasias da Vesícula Biliar/terapia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Quimioterapia Adjuvante , Adulto , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Intervalo Livre de Doença , Carcinoma Adenoescamoso/terapia , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologiaRESUMO
ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.
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Laparoscopia , Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Reto/patologia , Laparoscopia/métodos , Terapia Neoadjuvante , Segunda Neoplasia Primária/cirurgiaRESUMO
PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).
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Adenocarcinoma , Sistema Biliar , Adulto , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Sistema Biliar/metabolismo , Cisplatino , Classe I de Fosfatidilinositol 3-Quinases/genética , Desoxicitidina , Gencitabina , Hibridização in Situ Fluorescente , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêuticoRESUMO
Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.
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PURPOSE: The current study was conducted to examine the role of consolidation chemotherapy after neoadjuvant radiation therapy (NART) in decreasing the involvement of the mesorectal fascia (MRF) in high-risk locally advanced rectal cancers (LARCs). METHODS: In total, 46 patients who received consolidation chemotherapy after NART due to persistent MRF involvement were identified from a database. A team of 2 radiologists, blinded to the clinical data, studied sequential magnetic resonance imaging (MRI) scans to assess the tumor response and then predict a surgical plan. This prediction was then correlated with the actual procedure conducted as well as histopathological details to assess the impact of consolidation chemotherapy. RESULTS: The comparison of MRI-based parameters of sequential images showed significant downstaging of T2 signal intensity, tumor height, MRF involvement, diffusion restriction, and N category between sequential MRIs (P < 0.05). However, clinically relevant downstaging (standardized mean difference, > 0.3) was observed for only T2 signal intensity and diffusion restriction on diffusion-weighted imaging. No clinically relevant changes occurred in the remaining parameters; thus, no change was noted in the extent of surgery predicted by MRI. Weak agreement (Cohen κ coefficient, 0.375) and correlation (Spearman rank coefficient, 0.231) were found between MRI-predicted surgery and the actual procedure performed. The comparison of MRI-based and pathological tumor response grading also showed a poor correlation. CONCLUSION: Evidence is lacking regarding the use of consolidation chemotherapy in reducing MRF involvement in LARCs. The benefit of additional chemotherapy after NART in decreasing the extent of planned surgery by reducing margin involvement requires prospective research.
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Lung cancer is the most diagnosed cancer worldwide. Many non-malignant pulmonary lesions, such as tuberculosis, fungal infection, organizing pneumonia, inflammatory myofibroblastic tumor, and IgG4 disease, can mimic lung cancer due to their overlapping morphological appearance on imaging. These benign entities with minor differentiating imaging clues may go unnoticed in a high-volume cancer institution, leading to over-investigation that may result in repeated biopsies, pointless wedge resections, and related morbidities. However, with a thorough medical history, laboratory diagnostic work-up, and careful analysis of imaging findings, one can occasionally restrict the range of possible diagnoses or arrive at a definitive conclusion. When imaging features overlap, image-guided lung sampling is crucial since histopathological analysis is the gold standard.
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Neoplasias Pulmonares , Pneumonia , Humanos , Atenção Terciária à Saúde , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/patologia , Pulmão/patologia , Pneumonia/patologiaRESUMO
Melanotic pigment in the thyroid is practically synonymous with chronic minocycline therapy and rare cases of melanotic medullary thyroid carcinoma. However, primary melanoma of the thyroid has not been reported yet. We report a rare case of a 25-year-old male with a locally aggressive thyroid mass and distant metastases at presentation. Radiologically, a 8.3×7.6-cm nodule was identified in the right thyroid lobe. Fine-needle aspiration cytology (FNAC) showed discohesive atypical plasmacytoid cells with prominent nucleoli and no cytoplasmic pigmentation. Serum calcitonin levels were normal. A trucut biopsy showed a malignant tumor with a similar cytomorphology, including marked nuclear pleomorphism. In addition, intracytoplasmic melanin was seen in <1% of cells. Tumor cells were immunonegative for AE1/AE3, TTF1, synaptophysin, and chromogranin while positive for SOX10, S100P, HMB45, and Melan A, confirming the diagnosis of malignant melanoma, without any detectable MTC component in the biopsy. An HRAS G13R mutation was detected on NGS, which, intriguingly, is a known mutation in MTC, and exceedingly rare in melanocytic lesions. No other clinically or radiologically apparent primary lesion was identified elsewhere in the patient. The unusual histology and hitherto unreported molecular findings make this case of primary thyroid melanocytic neoplasm worth reporting. Abstruse origin of melanoma cells in the thyroid gland with molecular signature suggestive of MTC in our case raises a nomenclature and management conundrum, prompting us to revisit the "ontogeny recapitulates phylogeny" theory.
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PURPOSE: Evaluate MR patterns of response and their evolution in rectal cancer patients on watch and wait (WW). METHODS: We retrospectively reviewed 337 MRIs of 60 patients (median follow-up: 12 months; range: 6-49 months). Baseline MRIs (available in 34/60 patients) were evaluated for tumor morphology, location, thickness, circumferential involvement, nodal status and EMVI. First post-treatment MRIs (in all patients) were additionally evaluated for pattern of response on T2 and DWI. Change in post-treatment scar thickness and scar depth angle between the first and second post-treatment scans was also evaluated. Evolution of the response pattern/recurrence were evaluated till the last available scan. RESULTS: On the baseline scans, 20/34 (59%) patients had polypoidal tumor with 12/20 having ≤ 25% circumferential wall involvement. We saw five patterns of response-normalized rectal wall (2/60-3%), minimal fibrosis (23/60-38%), full thickness fibrosis (16/60-27%), irregular fibrosis (11/60-18%) and split scar (6/60-10%), with 2/60 (3%) showing possible residual disease. On the first post-treatment scans, 12/60 (20%) had restricted diffusion, with 3/12 having persistent restriction till last follow-up. Post-treatment fibrosis/split scar remained stable in 44/60 (73%) cases and improved further in the rest. 9/60 (15%) patients developed regrowth/recurrence. Patients with recurrence had < 10 mm scar thickness and < 21° change in scar angle between the first and second post-treatment MRIs. CONCLUSION: Most patients on WW protocol developed minimal or full thickness fibrosis, majority of which remained stable on follow-up.
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Metastasis to the thyroid gland is very uncommon with an incidence of 2-3% of all thyroid malignancies. A higher incidence is noted in autopsy studies indicating incidental detection. However, tumour-to-tumour metastasis is extremely uncommon with a handful of cases published in the literature to date. Also, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P) is a rare neoplasm; diagnosis requires meticulous sampling of the entire capsule and fulfilment of other diagnostic criteria. We report a case of primary adenocarcinoma of lung in a 57-year-old female who additionally had a left thyroid nodule which appeared suspicious on ultrasonography. Histology of lung tumour was conventional papillary adenocarcinoma while aspiration cytology from the thyroid raised suspicion of metastatic adenocarcinoma. On hemithyroidectomy, the thyroid nodule showed metastatic adenocarcinoma in the centre of the nodule, while the peripheral portion showed non-invasive follicular thyroid neoplasm with papillary-like nuclear features; the diagnosis of which was confirmed with complete sampling of the thyroid capsule. The immunoprofile also supported the above dual histology. This is an extremely uncommon occurrence and metastasis within a NIFT-P has not been reported to the best of our knowledge.
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Adenocarcinoma de Pulmão , Adenocarcinoma Folicular , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/patologia , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias Pulmonares/diagnósticoRESUMO
CONTEXT.: Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. OBJECTIVE.: To study the detailed clinicopathologic features of PABOT. DESIGN.: Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. RESULTS.: Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI-type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI-like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non-GI-type case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear ß-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). CONCLUSIONS.: We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories.
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This study's objective was to compare detection rates of radiograph, computed tomography (CT), and positron emission tomography-contrast-enhanced computed tomography (PET-CECT) for pulmonary metastasis/synchronous primary lung tumors in head and neck squamous cell cancer (HNSCC) and its association with clinico-radio-pathological factors. Our retrospective study included 837 HNSCC patients from January 2012 to December 2017. Lung nodules were characterized on CT as benign, indeterminate, and metastatic. The true detection rate and statistical significance of associated risk factors were calculated. Risk factors for metastasis were determined using univariate and multivariate logistic regression models. Seventy-five (8.9%) patients had pulmonary metastasis and 3 (0.3%) had second lung primary. Detection rate of pulmonary metastasis by CT was higher (sensitivity-97.3%, specificity-97.2%) as compared to radiograph (sensitivity 49% and specificity 89%). Correlation was found between pulmonary and extra-pulmonary metastasis and N classification (P = 0.01, P = 0.02) and positive low jugular node (P = 0.001, P = 0.001). Using PET-CECT in place of CT costed an extra outlay of 7,033,805 INR (95,551.85 USD) while detecting distant metastasis in only 4 (0.47%) extra cases. Chest CT is a useful pulmonary metastases screening tool in advanced HNSCC patients with reasonable imaging cost as compared to PET-CT.
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Parathyroid cancer is a rare endocrine malignancy with only a few thousand cases reported worldwide. As a result, there exists considerable controversy regarding the various aspects of this disease, viz., etiology, diagnosis, and management. We hereby attempt to review the literature on parathyroid carcinoma (PC) and summarize the practices based on the current evidence available. The majority of the PC are sporadic although an association with hyperparathyroidism-jaw tumor syndrome, multiple endocrine neoplasia (MEN) 1 and 2, and isolated familial hyperparathyroidism has been shown. As preoperative diagnosis is challenging, PC should be suspected in patients presenting with a neck mass with signs and symptoms of invasion to surrounding structures. Skeletal and renal symptoms are often associated with PC as presenting complaints. The biochemical parameters are more pronounced in the case of PC compared with benign countpart. Due to its rarity, the American Joint Committee of cancer control (AJCC) acknowledges that as yet a clear distinct staging system to prognosticate the disease would be premature. Complete excision with negative margins at first surgery offers the best chance of cure. The role of radiotherapy (RT) is still unclear; however few series have suggested a better locoregional control with adjuvant RT. Recurrences are common and are most significantly associated with an incomplete clearance at initial surgery. Surgical salvage of recurrent/metastatic disease with medical management of hypercalcemia is the treatment of choice. Large prospective studies and trials need to be conducted to understand the pathology better and improve management protocols; however this is a challenge due to rarity of cases.
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BACKGROUND: This phase I dose de-escalation study aimed to assess the tolerability, safety, pharmacokinetics (PK), and efficacy of sequentially decreasing doses of sorafenib in combination (SAM) with atorvastatin (A, 10 mg) and metformin (M, 500 mg BD) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients were enrolled in 1 of 4 sequential cohorts (10 patients each) of sorafenib doses (800 mg, 600 mg. 400 mg, and 200 mg) with A and M. Progression from one level to the next was based on prespecified minimum disease stabilization (at least 4/10) and upper limits of specific grade 3-5 treatment-related adverse events (TRAE). RESULTS: The study was able to progress through all 4 dosing levels of sorafenib by the accrual of 40 patients. Thirty-eight (95%) patients had either main portal vein thrombosis or/and extra-hepatic disease. The most common grade 3-5 TRAEs were hand-foot-syndrome (grade 2 and grade 3) in 3 (8%) and transaminitis in 2 (5%) patients, respectively. The plasma concentrations of sorafenib peaked at 600 mg dose, and the concentration threshold of 2400 ng/mL was associated with higher odds of achieving time to exposure (TTE) concentrations >75% centile (odds ratio [OR] = 10.0 [1.67-44.93]; P = .01). The median overall survival for patients without early hepatic decompensation (n = 31) was 8.9 months (95% confidence interval [CI]: 3.2-14.5 months). CONCLUSION: The SAM combination in HCC patients with predominantly unfavorable baseline disease characteristics showed a marked reduction in sorafenib-related side effects. Studies using sorafenib 600 mg per day in this combination along with sorafenib drug level monitoring can be evaluated in further trials.(Trial ID: CTRI/2018/07/014865).
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Metformina , Antineoplásicos/efeitos adversos , Atorvastatina/uso terapêutico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Metformina/farmacologia , Metformina/uso terapêutico , Niacinamida , Compostos de Fenilureia/uso terapêutico , Sorafenibe/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: Rectovaginal fistulas (RVFs) are an uncommon and disturbing complication with limited success in treatment. This study was aimed at determining the incidence of RVFs after rectal resections in the era of neoadjuvant radiation therapy and the outcomes of their treatment. METHODS: This was a retrospective study of female patients who underwent sphincter-preserving total mesorectal excision for rectal cancer and developed RVF. RESULTS: Four hundred eighty-eight patients underwent rectal resections between January 2013 and December 2019, and 9 developed RVF (1.8%). Average time to presentation was 280 days (range, 6-540 days). The median time to onset for those presenting prior to stoma reversal was 90 days, whereas the duration between stoma reversal and RVF detection in those presenting after stoma closures was 115 days. Success rates of fecal diversion and local procedures for treatment of RVF were 20% (2/10 procedures) and 40% (2/5 procedures), respectively. Redo coloanal anastomosis was performed for 2 patients with successful outcome. An average of 2.1 procedures were performed per patient (19/9) with a per-procedure success rate of 31.6% (6/19 procedures) and a per-patient success rate of 66.7% (6/9). At median follow-up of 64 months, 50% (3/6) of patients with a healed fistula were free of stoma, and all of them were continent. Four patients were sexually active. CONCLUSIONS: The incidence of RVF after rectal resection is low, but treatment outcomes are disappointing. Diversions and local repairs had high failure rates in our patients where the majority received preoperative radiation therapy. After successful healing, sexual function and continence are acceptable.
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Neoplasias Retais , Fístula Retovaginal , Feminino , Humanos , Incidência , Neoplasias Retais/cirurgia , Fístula Retovaginal/epidemiologia , Fístula Retovaginal/etiologia , Fístula Retovaginal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Comparative bowel functional outcomes between ultralow anterior resections (ULAR) and inter-sphincteric resection (ISR) for similar tumour and patient characteristics is not known. METHODS: Single centre study of low rectal caners (<5cm from anal verge) with 1:1 propensity matching of age, sex, body mass index, prior radiation, and surgical approach (open vs. minimally invasive) was performed for the ULAR and ISR groups. Primary outcome measure was Wexner Incontinence scores and Low Anterior Resection Syndrome (LARS) score at a single time point after stoma reversal. RESULTS: Seventy-two matched patients were included. Median Wexner scores were five and eight for the ULAR and ISR cohorts (p = 0.006). Major incontinence (Wexner >11) was found in 5.6% versus 33% after ULAR and ISR, respectively. Major LARS (score > 29) was demonstrated in 11% versus 25% in ULAR versus ISR (p = 0.293). Majority in both groups has no LARS (score < 20), that is, 72.2% versus 63.9% in ULAR against ISR. Besides these, stool fragmentation (p < 0.001), nocturnal defecation (p < 0.001) and use of anti-diarrhoeal medications (p = 0.023) were significantly more after ISR. CONCLUSIONS: Bowel continence was relatively inferior after ISR as compared to an ULAR for low rectal cancers in matched cohorts. Major LARS in ISR was twice as prevalent without statistical differences.
Assuntos
Protectomia , Neoplasias Retais , Canal Anal/patologia , Canal Anal/cirurgia , Humanos , Complicações Pós-Operatórias , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , SíndromeRESUMO
INTRODUCTION: Lateral pelvic lymph node dissection (LPLND) is a technically challenging procedure and its learning curve has not been analysed against an oncologically relevant outcome. The purpose of the study was to determine the learning curve for LPLND in rectal cancers using nodal retrieval as performance measure. METHODS: Consecutive LPLND for rectal adenocarcinomas from a single institution were retrospectively analysed. Cumulative sum (CUSUM) control charts were used to detect difference in performance with respect to lymph node yield. Negative binomial regression was used to determine factors influencing nodal harvest using Incidence Risk Ratios (IRR). Separate CUSUM curves were generated for open and minimally invasive surgeries (MIS). RESULTS: One-hundred and twenty patients were included and all received preoperative radiation. MIS was used in 53.3%. Median lymph node yield was 6 with 20% nodal positivity. Increasing experience (IRR - 1.196) and MIS (IRR - 1.586) were the only factors that influenced nodal harvest. CUSUM charts revealed that learning curve was achieved after the 83rd case overall and after the 19 operations in MIS. There was a 20% increase in nodal yield after every 30 MIS LPLND performed. CONCLUSIONS: Learning curve for LPLND is relatively long and only increasing experience and minimally invasive operations increased nodal yield.
Assuntos
Curva de Aprendizado , Neoplasias Retais , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/patologia , Estudos RetrospectivosRESUMO
Ossifying fibromas of the head and neck region are classified as cemento-ossifying fibroma (COF) (odontogenic origin), and two types of juvenile ossifying fibromas: juvenile trabecular ossifying fibroma (JTOF), and juvenile psammomatous ossifying fibroma (JPOF). The potential for recurrence in JTOF and JPOF and the discovery of newer molecular signatures necessitates accurate histological classification. Over 12 years (2005-2017), a total of 45 patients with 51 tumours were retrieved and reviewed for clinic-pathological features from the archives of a tertiary care oncology centre. Of 45 cases, COF, JTOF and JPOF comprised 13 (28.9%), 11 (24.4%) and 18 (40%) cases respectively. Three cases were unclassifiable. M: F ratio was 1:3.3, 1.1:1, 2:1 for COF, JTOF and JPOF respectively with an age range of 6-66 years (mean: 24.6, median; 18.1 years). The most common site for COF was mandible, for JTOF was maxilla, and for JPOF was ethmoid sinus. One case of mixed JTOF and JPOF histology was seen. Aneurysmal bone cyst-like areas were seen in 26.6% of cases, most commonly in JPOF. Follow up was available in 23 cases, and ranged from 4 to 207 months. Three cases of JPOF had a recurrence and one patient with JTOF had residual disease after surgery. One case of COF demonstrated increased parathyroid hormone levels. COF, JTOF, and JPOF are clinically, radiologically and histologically distinct entities. Surgical resection is the mainstay of treatment. JPOF has a higher incidence of recurrence as compared to JTOF and COF and hence needs a more aggressive follow-up.