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1.
Cureus ; 13(8): e17395, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34462709

ABSTRACT

The biopsychosocial (BPS) model proposed by George Engel posited that a disease developed through a complex interaction of biological, psychological and social factors. This popular model, despite its limitations, continues to influence the practice and treatment of illness and service delivery worldwide. We propose the networked computer metaphor as a novel and pragmatic tool to help psychiatric trainees appreciate and enhance the utility of the BPS model as it pertains to psychiatric disorders. We also propose that the application of this metaphor would help provide some clues to answer the question of achieving the goal envisioned by Engel of providing holistic and comprehensive patient-centered care. We also discuss the utility of this metaphor from trainee, teacher and patient perspectives and describe various examples of the application of this metaphor so as to deepen our understanding of the BPS model. We discuss the criticisms of this model, summarize the applications of this metaphor and outline future directions for research.

2.
Cureus ; 13(4): e14564, 2021 Apr 19.
Article in English | MEDLINE | ID: mdl-34026380

ABSTRACT

Major depression is a chronic debilitating condition affecting people of all ages and is rising over the past decade. Major depression among children and adolescents is often resistant to traditional treatments, thus necessitating the exploration of novel strategies. Repetitive transcranial magnetic stimulation (rTMS) is gaining increasing attention as a useful tool in treating various conditions and has received the US Food and Drug Administration (FDA) approval to treat depression and obsessive-compulsive disorder among adults. Favorable outcomes among adults generated interest in using it among children. Until recently, the existing literature lacked randomized sham-controlled trials on this topic among children and adolescents. The newest additions in the literature necessitated another in-depth look at the data to explore the safety and efficacy of rTMS in the context of depression among children and adolescents. We searched the Medline and Cochrane databases and included 18 articles for our systematic review. Our systematic review indicates level 1 evidence that rTMS is safe but failed to show its superiority to placebo as a stand-alone treatment for resistant depression among children and adolescents. However, there is level 2 evidence favoring add-on rTMS to treat major depression among children and adolescents. The study subjects appear to tolerate the rTMS treatment well with some minor and mostly self-limited side effects. Risks of treatment-emergent hypomanic symptoms and seizure appear to be very low. There is no evidence of worsening of suicidal ideation or cognitive decline during rTMS treatment.

3.
Psychiatr Clin North Am ; 44(2): 249-261, 2021 06.
Article in English | MEDLINE | ID: mdl-34049647

ABSTRACT

Multiple-choice tests are the most used method of assessment in medical education. However, there is limited literature in medical education and psychiatry to inform the best practices in writing good-quality multiple-choice questions. Moreover, few physicians and psychiatrists have received training and have experience in writing them. This article highlights the strategies in writing high-quality multiple-choice items and discusses some common flaws that can impact validity and reliability of the assessment examinations.


Subject(s)
Education, Medical , Educational Measurement , Humans , Reproducibility of Results , Writing
4.
Oncology ; 94(6): 345-353, 2018.
Article in English | MEDLINE | ID: mdl-29705797

ABSTRACT

OBJECTIVE: The goal of surveillance after therapy of localized esophageal cancer (LEC) is to identify actionable relapses amenable to salvage; however, the current surveillance algorithms are not optimized. We report on a large cohort of LEC patients with actionable locoregional relapses (LRRs). METHODS: Between 2000 and 2013, 127 (denominator = 752) patients with actionable LRR were identified. Histologic/cytologic confirmation was the gold standard. All surveillance tools (imaging, endoscopy, fine needle aspiration) were assessed. RESULTS: Most patients were men (89%), had adenocarcinoma (79%), and had no new symptoms (72%) when diagnosed with LRR. In trimodality patients, endoscopic confirmation of positron emission tomography-computed tomography-suspected LRR occurred in only 44%, and 56% required additional tools (e.g., fine needle aspiration). Alternatively, in bimodality patients, endoscopy confirmed LRRs in 81%. Trimodality patients had a higher risk of subsequent LRR/distant metastases after the first LRR than the bimodality patients (p = 0.03). In all patients, 78% of the subsequent relapses were distant. For patients who were salvaged, survival was significantly prolonged (50.6 vs. 25.1 months, p < 0.01). CONCLUSIONS: Patients live longer after successful salvage of the LRR than if salvage is not possible. After LRR, patients have a high risk of subsequent distant metastasis and whether the second relapse is local or distant, survival is uniformly poor.


Subject(s)
Adenocarcinoma/pathology , Esophageal Neoplasms/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/diagnosis , Salvage Therapy/methods , Adenocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Esophageal Neoplasms/drug therapy , Female , Humans , Male , Middle Aged , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Positron Emission Tomography Computed Tomography
5.
Am J Clin Oncol ; 41(4): 321-325, 2018 04.
Article in English | MEDLINE | ID: mdl-26908161

ABSTRACT

BACKGROUND: A randomized phase III study established docetaxel, cisplatin, and 5-fluorouracil (DCF) as one of the standard treatments for patients with untreated advanced gastric cancer (AGC). However, DCF use is limited due toxicity. With the purpose to evaluate a less toxic regimen, we conducted a single arm, phase I/II trial of modified DCF (oxaliplatin, 5-fluorouracil, and docetaxel [D-FOX]) for untreated AGC patients. The primary objective of the phase I study was to determine the maximum tolerated dose of docetaxel and for the phase II study was to assess the progression-free survival (PFS) at 6 months and overall survival (OS). PATIENTS AND METHODS: We enrolled a total of 98 patients with AGC. Docetaxel and oxaliplatin were administered intravenously on day 1 and 5-fluorouracil was infused starting on day 1 over 48 hours. Cycles were repeated every 2 weeks and patients were monitored for toxicities. Kaplan-Meir curve was used to estimate unadjusted OS and PFS. RESULTS: The maximum tolerated dose of docetaxel was 50 mg/m. In total, 24 (45%) patients experienced grade 2 adverse events, 22 (41%) experienced grade 3, and 1 (1.9%) experienced grade 4 toxicity. The median PFS in the phase II portion of the study was approximately 6.5 (95% confidence interval, 5.5-9.5) months and the median OS was 11.1 (95% confidence interval, 9.4-18.8) months. CONCLUSIONS: D-FOX administered every 2 weeks is a well-tolerated and active regimen in untreated AGC patients.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophagogastric Junction/drug effects , Stomach Neoplasms/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Docetaxel/administration & dosage , Esophagogastric Junction/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Oxaliplatin/administration & dosage , Prognosis , Prospective Studies , Stomach Neoplasms/pathology , Survival Rate
6.
Oncotarget ; 8(46): 81430-81440, 2017 Oct 06.
Article in English | MEDLINE | ID: mdl-29113402

ABSTRACT

PURPOSE: After therapy of localized gastric adenocarcinoma (GAC) patients, the costs of surveillance, relapse patterns, and possibility of salvage are unknown. MATERIALS AND METHODS: We identified 246 patients, who after having a negative peritoneal staging, received therapy (any therapy which included surgery) and were surveyed (every 3-6 months in the first 3 years, then yearly; ∼10 CTs and ∼7 endoscopies per patient). We used the 2016 Medicare dollars reimbursed as the "costs" for surveillance. RESULTS: Common features were: Caucasians (57%), men (60%), poorly differentiated histology (76%), preoperative chemotherapy (74%), preoperative chemoradiation (59%), and had surgery (100%). At a median follow-up of 3.7 years (range, 0.1 to 18.3), the median overall survival (OS) was 9.2 years (95% CI, 6.0 to 11.2). Tumor grade (p = 0.02), p/yp stage (p < 0.001), % residual GAC (p = 0.05), the R status (p = 0.01), total gastrectomy (p = 0.001), and relapse type (p = 0.02) were associated with OS. Relapse occurred in 79 (32%) patients (only 8% were local-regional) and 90% occurred within 36 months of surgery. P/yp stage (p < 0.001) and total gastrectomy (p = 0.01) were independent prognosticators for OS in the multivariate analysis. Only 1 relapsed patient had successful salvage therapy. The estimated reimbursement for imaging studies and endoscopies was $1,761,221.91 (marked underestimation of actual costs). CONCLUSIONS: The median OS of localized GAC patients was excellent with infrequent local-regional relapses. Rigorous surveillance had a low yield and high "costs". Our data suggest that less frequent surveillance intervals and limiting expensive investigations to symptomatic patients may be warranted.

7.
Br J Cancer ; 117(5): 648-655, 2017 Aug 22.
Article in English | MEDLINE | ID: mdl-28728163

ABSTRACT

BACKGROUND: Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it. METHODS: Untreated OC tissues from patients who underwent chemoradiation and surgery were assessed for nuclear Gli-1 by immunohistochemistry and labelling indices (LIs) were correlated with pathologic complete response (pathCR) or

Subject(s)
Adenocarcinoma/chemistry , Adenocarcinoma/therapy , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/therapy , Cell Nucleus/chemistry , Chemoradiotherapy, Adjuvant , Esophageal Neoplasms/chemistry , Esophageal Neoplasms/therapy , Zinc Finger Protein GLI1/analysis , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , CRISPR-Cas Systems , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Epidemiologic Methods , Esophageal Neoplasms/pathology , Esophagectomy , Female , Gene Editing , Hedgehog Proteins/analysis , Hedgehog Proteins/genetics , Humans , Male , Middle Aged , Neoadjuvant Therapy , RNA, Messenger/metabolism , Radiation Tolerance , Zinc Finger Protein GLI1/antagonists & inhibitors , Zinc Finger Protein GLI1/genetics
8.
Chin J Cancer ; 35(1): 69, 2016 07 26.
Article in English | MEDLINE | ID: mdl-27460019

ABSTRACT

Surgical management of gastric cancer improves survival. However, for some time, surgeons have had diverse opinions about the extent of gastrectomy. Researchers have conducted many clinical studies, making slow but steady progress in determining the optimal surgical approach. The extent of lymph node dissection has been one of the major issues in surgery for gastric cancer. Many trials demonstrated that D2 dissection resulted in greater morbidity and mortality than D1 dissection. However, long-term outcomes demonstrated that D2 dissection resulted in longer survival than D1 dissection. In 2004, the Japan Clinical Oncology Group reported a pivotal trial which was performed to determine whether para-aortic lymph node dissection combined with D2 dissection was superior to D2 dissection alone and found no benefit of the additional surgery. Gastrectomy with pancreatectomy, splenectomy, and bursectomy was initially recommended as part of the D2 dissection. Now, pancreas-preserving total gastrectomy with D2 dissection is standard, and ongoing trials are addressing the role of splenectomy. Furthermore, the feasibility and safety of laparoscopic gastrectomy are well established. Survival and quality of life are increasingly recognized as the most important endpoints. In this review, we present perspectives on surgical techniques and important trials of these techniques in gastric cancer patients.


Subject(s)
Gastrectomy/methods , Lymph Node Excision/methods , Stomach Neoplasms/surgery , Humans , Prognosis
9.
Oncology ; 90(5): 239-47, 2016.
Article in English | MEDLINE | ID: mdl-27046280

ABSTRACT

BACKGROUND: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. METHODS: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or

Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Signet Ring Cell/therapy , Chemoradiotherapy , Neoadjuvant Therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Adult , Aged , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Grading , Neoplasm Staging , Predictive Value of Tests , Preoperative Period , Prognosis , Treatment Outcome
10.
Oncology ; 91(1): 55-60, 2016.
Article in English | MEDLINE | ID: mdl-27120436

ABSTRACT

OBJECTIVE: Patients with metastatic gastroesophageal adenocarcinoma (MGEAC) have a poor but heterogeneous clinical course. Some patients have an unusually favorable outcome. We sought to identify clinical variables associated with more favorable outcomes. METHODS: Of 246 patients with MGEAC, we identified 64 who received systemic therapy and eventually received local consolidation therapy. Univariate and multivariate Cox regression models were used, and a nomogram was developed. RESULTS: Of these 64 patients, 61% had received consolidation chemoradiation (CRT) with doses of 50-55 Gy and 78% did not undergo surgery. The median follow-up time of survivors was 3.9 years, and the median overall survival (OS) from CRT start was 1.5 years (95% CI, 1.2-2.2). Surgery (as local consolidation) was an independent prognosticator for longer OS in the multivariate analysis (p = 0.02). The 5-year OS rate was 25% (SE = 6%). The contributors to the nomogram were longer duration of systemic therapy before CRT and the type of local therapy. CONCLUSIONS: Our data suggest that a subset of patients with MGEAC have an excellent prognosis (OS >5 years). However, these patients need to be identified during their clinical course so that local consolidation (CRT, surgery, or both) may be offered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Esophagogastric Junction/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/radiotherapy , Adult , Aged , Esophageal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Nomograms , Organoplatinum Compounds/administration & dosage , Pyrimidines/administration & dosage , Retrospective Studies , Stomach Neoplasms/pathology , Survivors , Taxoids/administration & dosage
11.
J Natl Compr Canc Netw ; 14(2): 173-9, 2016 02.
Article in English | MEDLINE | ID: mdl-26850487

ABSTRACT

BACKGROUND: Among patients with localized esophageal cancer (LEC), 35% or more develop distant metastases (DM) as first relapse, most in the first 24 months after local therapy. Implementation of novel strategies may be possible if DM can be predicted reliably. We hypothesized that clinical variables could help generate a DM nomogram. PATIENTS AND METHODS: Patients with LEC who completed multimodality therapy were analyzed. Various statistical methods were used, including multivariate analysis to generate a nomogram. A concordance index (c-index) was established and validated using the bootstrap method. RESULTS: Among 629 patients analyzed (356 trimodality/273 bimodality), 36% patients developed DM as first relapse. The median overall survival from DM was only 8.6 months (95% CI, 7.0-10.2). In a multivariate analysis, the variables associated with a higher risk for developing DM were poorly differentiated histology (hazard ratio [HR], 1.76; P<.0001), baseline T3/T4 primary (HR, 3.07; P=.0006), and baseline N+ LEC (HR, 2.01; P<.0001). Although variables associated with a lower risk for DM were age of 60 years or older (HR, 0.75; P=.04), squamous cell carcinoma (HR, 0.54; P=.013), and trimodality therapy (HR, 0.58; P=.0001), the bias-corrected c-index was 0.67 after 250 bootstrap resamples. CONCLUSIONS: Our nomogram identified patients with LEC who developed DM with a high probability. The model needs to be refined (tumor and blood biomarkers) and validated. This type of model will allow implementation of novel strategies in patients with LEC.


Subject(s)
Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/pathology , Adult , Aged , Aged, 80 and over , Combined Modality Therapy/methods , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Nomograms , Young Adult
12.
Eur J Cancer ; 51(17): 2545-52, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26321501

ABSTRACT

INTRODUCTION: The purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS). MATERIALS AND METHODS: Thirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUV max) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS. RESULTS: Among the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9-NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively). CONCLUSION: None of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/therapy , Multimodal Imaging/methods , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Bridged-Ring Compounds/administration & dosage , Chemoradiotherapy/methods , Esophageal Neoplasms/diagnosis , Female , Fluorodeoxyglucose F18 , Fluorouracil/administration & dosage , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Oxaliplatin , Prognosis , Proportional Hazards Models , Prospective Studies , Remission Induction , Taxoids/administration & dosage
13.
Oncology ; 89(6): 305-10, 2015.
Article in English | MEDLINE | ID: mdl-26393501

ABSTRACT

BACKGROUND: In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS). METHODS: We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis. RESULTS: The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (≤ 6; p = 0.0017). Patients with a high iSUV (> 6) had a longer OS compared to those with a low iSUV (≤ 6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV > 6 (hazard ratio = 0.26). CONCLUSION: Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Fluorodeoxyglucose F18/pharmacokinetics , Positron-Emission Tomography , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Preoperative Care , Prognosis , Prospective Studies , Radiopharmaceuticals/pharmacokinetics , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Survival Rate , Tissue Distribution
14.
Oncology ; 89(4): 215-20, 2015.
Article in English | MEDLINE | ID: mdl-26159599

ABSTRACT

BACKGROUND: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. METHODS: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. RESULTS: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (≥ 4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). CONCLUSION: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection.


Subject(s)
Antineoplastic Agents/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
15.
J Natl Compr Canc Netw ; 13(4): e19-29, 2015 Apr.
Article in English | MEDLINE | ID: mdl-26052595

ABSTRACT

Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.


Subject(s)
Biomarkers, Tumor , Molecular Targeted Therapy , Stomach Neoplasms , Adaptor Proteins, Signal Transducing , Aldehyde Dehydrogenase 1 Family , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , ErbB Receptors , Hedgehog Proteins , Hippo Signaling Pathway , Humans , Isoenzymes , Neovascularization, Pathologic/prevention & control , Phosphatidylinositol 3-Kinases , Phosphoproteins , Prognosis , Programmed Cell Death 1 Receptor , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins c-met , Receptor, ErbB-2 , Receptors, Fibroblast Growth Factor , Receptors, Vascular Endothelial Growth Factor , Retinal Dehydrogenase , SOX9 Transcription Factor , Signal Transduction , Stomach Neoplasms/chemistry , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , TOR Serine-Threonine Kinases , Transcription Factors , Vascular Endothelial Growth Factor A , YAP-Signaling Proteins
16.
Expert Opin Pharmacother ; 16(7): 955-60, 2015 May.
Article in English | MEDLINE | ID: mdl-25850442

ABSTRACT

Gastric cancer (GC) continues to be a significant problem worldwide and is the third leading cause of cancer death. Armamentarium to treat GC whether it is potentially curable or metastatic (incurable) has changed little over the last decades with only two new agents being approved (trastuzumab and ramucirumab). Many relatively healthy patients after second-line therapy have limited and generally ineffective options. The recent The Cancer Genome Atlas analysis has uncovered four genotypes of GC; however, it is not sufficient to change our treatment strategies and more work needs to be done. The popular front-line regimen containing a platinum compound and a fluoropyrimidine is widely used for drug development and has worked well globally. Thus, this combination appears suitable for adding a biologic agent. The search for new classes of cytotoxics has almost stopped, but it is clear that cytotoxic therapy continues to contribute and it is here to stay. Biologic agents that modulate the immune system of the host appear promising along with many other biologics that can potentially inhibit signaling pathways that are often employed by GC cells. We will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and MET pathways.


Subject(s)
Antineoplastic Agents/therapeutic use , Biological Products/therapeutic use , Stomach Neoplasms/drug therapy , Antibodies, Monoclonal/therapeutic use , Clinical Trials, Phase III as Topic , Drug Therapy, Combination , Humans , Molecular Targeted Therapy , Neoplasm Metastasis , Randomized Controlled Trials as Topic , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology
17.
Oncology ; 89(2): 65-9, 2015.
Article in English | MEDLINE | ID: mdl-25765719

ABSTRACT

BACKGROUND: We have limited knowledge of the geographic distribution of resistant esophageal adenocarcinoma (EAC) in resected specimens, but its clinical importance can be enormous. METHOD: We selected patients with baseline stage III EAC who had had chemoradiation followed by surgery and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (percentage of resistant EAC and anatomic distribution). RESULTS: A total of 100 clinical stage III patients were studied; 90% had an R0 resection, and 99% had either moderate or poorly differentiated EAC. Twelve percent had >50% residual cancer, 31% had 11-50% residual cancer, 53% had 1-10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa (66%), muscularis propria (76%), and serosa (62%); all compartments were involved in 35% of the cases. Lack of EAC (meaning response) was observed in the mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery showed no EAC in 79% of the patients, in the surgical specimens, resistant EAC was frequently occurring in the mucosa/submucosa (66%). CONCLUSION: Contrary to our hypothesis that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the postchemoradiation biopsies are misleading, and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients.


Subject(s)
Adenocarcinoma/pathology , Esophageal Neoplasms/pathology , Lymphatic Metastasis/pathology , Mucous Membrane/pathology , Neoplasm, Residual/pathology , Serous Membrane/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Drug Resistance, Neoplasm , Esophageal Neoplasms/therapy , Female , Humans , Male , Middle Aged , Radiation Tolerance , Retrospective Studies , Survival Analysis , Treatment Outcome
18.
Oncology ; 88(6): 332-6, 2015.
Article in English | MEDLINE | ID: mdl-25765098

ABSTRACT

BACKGROUND/AIM: Malignant nodes in patients with localized esophageal adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the correlation of the distribution of nodes with the outcome of patients undergoing chemoradiation/surgery (trimodality therapy). METHODS: We studied 209 L-EAC patients who had confirmed or suspicious nodes at baseline staging. All patients received trimodality therapy and were grouped according to the nodal geography: above the diaphragm (AD), below the diaphragm (BD), or above and below the diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier method, and the outcomes of the groups were assessed by the log-rank test. RESULTS: Patients were primarily Caucasian (91%) and male (93%), with a baseline stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4-11.7). Of the 209 patients, 35% (n = 73) had AD nodes, 20% (n = 41) had BD nodes, and 45% (n = 95) had ABD nodes. ABD patients had a 5-year overall survival rate of 33%, whereas this rate was 55% in AD patients and 60% in BD patients (p = 0.02). Patients with a higher histology grade were also at a higher risk of relapse and had a poor survival (p < 0.01 for both). CONCLUSIONS: L-EAC patients in the ABD group had the worst outcome after trimodality treatment compared to those in the AD or BD group. Novel strategies are needed for ABD patients.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Adenocarcinoma/mortality , Adult , Aged , Chemoradiotherapy , Combined Modality Therapy , Esophageal Neoplasms/mortality , Esophagectomy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prognosis , Retrospective Studies , Survival Analysis
19.
World J Gastroenterol ; 20(38): 13637-47, 2014 Oct 14.
Article in English | MEDLINE | ID: mdl-25320502

ABSTRACT

Gastric cancer represents a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy (United States), pre-and post-operative chemotherapy (Europe), and adjuvant chemotherapy after a D2 resection (Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population, the treatments remain limited. In the first line setting, the standard of care is a combination of fluoropyrimidine and platinum containing chemotherapy, with or without epirubicin or docetaxel. The results of targeted therapy trials have by and large been disappointing, but none of these trials looked at an appropriately enriched population. Finally there is a meager overall survival benefit in treating patients with metastatic disease in the second line setting, with either irinotecan, docetaxel or ramucirumab however none of these drugs have been compared head to head in a well-powered randomized controlled trial.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Humans , Molecular Targeted Therapy , Neoadjuvant Therapy , Risk Factors , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis , Treatment Outcome
20.
J Clin Oncol ; 32(30): 3400-5, 2014 Oct 20.
Article in English | MEDLINE | ID: mdl-25225435

ABSTRACT

PURPOSE: Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies. PATIENTS AND METHODS: Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied. RESULTS: The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3). CONCLUSION: Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.


Subject(s)
Chemoradiotherapy , Esophageal Neoplasms/therapy , Salvage Therapy , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged
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