Frequency and prognostic utility of MSI and TILs in advanced noncolorectal GI malignancies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 313-313
Author(s):  
Uqba Khan ◽  
Ameer Hamza ◽  
Muhammad S Khurram ◽  
Renny Abraham ◽  
Paul Mazzara ◽  
...  

313 Background: Mismatch repair gene mutation status not only has a role in pathogenesis but also has significant clinical implications with respect to treatment with checkpoint inhibitors. Additionally tumor infiltrating lymphocytes (TILs) are also emerging prognostic biomarker and are utilized in adoptive T-cell therapy as well. Methods: This is a retrospective cohort study of patients who were diagnosed with advanced unresectable non-colorectal GI (NCGI) cancers. Biopsy specimens of patients diagnosed between 2009 and 2015 at St. John Hospital and Medical Center were analyzed. Immunohistochemistry panels were performed on a representative tissue sections for microsatellite instability (MSI) testing. TILs were assessed on the hematoxylin and Eosin stained slide of the same tissue section. MSI was interpreted as stable or high and TILs were categorized as ≤5 and > 5 per high power field. Descriptive statistics were generated using frequency distributions, medians and means. Kaplan-Meier analysis was performed to determine the impact of TILs and MSI on survival; differences by factor were assessed with the Log_Rank test. Results: We analyzed 114 patients; the mean age at diagnosis was 66.8 ± 10.7 years, 61.4% were male. All samples were MSI stable. The percentage of patients with TILs ≤ 5 was 46.5. When stratified by tumor stage, overall median survival by TILs level did not differ significantly. When stratified by type of tumor, overall median survival by TILs level was significantly different only for hepatocellular cancers (HCC) (≤ 5 TILs, 86 days vs. > 5 TILs 312 days, p = 0.031) only, (see table). Conclusions: Our study shows that MSI-H tumors are very rare in advanced NCGI malignancies. TILs are definitely present in tumor microenvironment of NCGI malignancies. Though the number of patients of our study was small, there was a statistically significant difference in median overall survival of patients with HCC when stratified by TILs status.[Table: see text]

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 89-89
Author(s):  
Uqba Khan ◽  
Ameer Hamza ◽  
Renny Abraham ◽  
Muhammad S Khurram ◽  
Tarik H. Hadid ◽  
...  

89 Background: Tumor infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with respect to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable non-colorectal GI (NCGI) cancers. Methods: This is a retrospective cohort study of patients who were diagnosed with metastatic or unresectable NCGI cancers between 2009 and 2015 at St. John Hospital and Medical Center. Immunohistochemistry panels were performed on representative tissue sections for MMR testing. TILs were assessed on the hematoxylin and eosin stained slide of the same tissue section. MMR was interpreted as deficient (d) or proficient and TILs were categorized as ≤5 or > 5 per high power field. Descriptive statistics were generated using frequency distributions, medians and means. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival; differences by factor were assessed with the Log_Rank test. Results: We analyzed 132 patients; the mean age at diagnosis was 66.7 years, 62.1% were male. All samples had proficient MMR status. The percentage of patients with TILs ≤ 5 was 46.2. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different only for hepatocellular cancers (HCC) (≤ 5 TILs, 86 days vs. > 5 TILs 312 days, p = 0.031), table 1. Conclusions: Our study suggests that MMR-d tumors are quite rare in advanced NCGI malignancies. TILs can be present in tumor microenvironment of NCGI malignancies. Though the number of patients in our study was small, there was a statistically significant difference in median OS of patients with HCC when stratified by TILs status.[Table: see text]


2018 ◽  
Vol 27 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Ameer Hamza ◽  
Uqba Khan ◽  
Muhammad Siddique Khurram ◽  
Renny Abraham ◽  
Paul Mazzara ◽  
...  

Background. Tumor-infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with regard to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable noncolorectal gastrointestinal (NCGI) malignancies. Methods. This is a retrospective cohort study of patients who were diagnosed with advanced noncolorectal gastrointestinal tumors. Biopsy specimens were tested for MMR status by immunohistochemistry along with evaluation of TILs. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival. Results. We analyzed 146 patients; the mean age at diagnosis was 66.4 ± 11.2 years. 65.8% patients were male, and 62.3% patients had stage 4 disease. All cases had proficient MMR status. The percentage of patients with TILs >5 was 50.7%. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different for hepatocellular cancers (⩽5 TILs, 86 days versus >5 TILs 312 days, P = .031). Conclusions. Our study suggests that MMR-deficient tumors are quite rare in advanced NCGI malignancies. More than 5 TILs per high power field, evaluated simply on a routine hematoxylin and eosin–stained glass slide confer a better prognosis to most noncolorectal gastrointestinal malignancies, especially hepatocellular carcinoma. This has immense clinical utility with regard to eligibility for immunotherapy.


2021 ◽  
Vol 164 (4) ◽  
pp. 781-787
Author(s):  
Samuel Rubin ◽  
Jacqueline A. Wulu ◽  
Heather A. Edwards ◽  
Robert W. Dolan ◽  
David M. Brams ◽  
...  

Objective Determine whether opioid prescriber patterns have changed for tonsillectomy, parotidectomy, and thyroidectomy after implementation of the Massachusetts Prescription Awareness Tool (MassPAT). Study Design Retrospective cohort study. Setting Single-center tertiary care hospital. Methods Patients were included if they received tonsillectomy, parotidectomy, or thyroid surgery at Lahey Hospital and Medical Center (Burlington, Massachusetts) between October 1, 2015, and October 1, 2019. Prescribing patterns were compared prior to implementation of MassPAT, October 1, 2015, to October 14, 2016, to postimplementation of MassPAT, October 15, 2016, to October 1, 2019. Quantity of opioids prescribed was described using total morphine milligram equivalents (MME). Data were analyzed using univariate analysis, multivariate analysis, and trend line using line of best fit. Results A total of 737 subjects were included in the study. There was a downward trend in the quantity of opioids prescribed for all 3 surgeries during the study period. There was a significant difference in the quantity of opioids prescribed pre- and postimplementation of MassPAT for tonsillectomy (647.70 ± 218.50 MME vs 474.60 ± 185.90 MME, P < .001), parotidectomy (241.20 ± 57.66 MME vs 156.70 ± 72.99 MME, P < .001), and thyroidectomy (171.20 ± 93.77 MME vs 108.50 ± 63.84 MME, P < .001). There was also a decrease in the number of patients who did not receive opioids for thyroidectomy pre- and post-MassPAT (7.56% vs 24.14%). Conclusion We have demonstrated that there is an association with state drug monitoring programs and decrease in the amount of opioids prescribed for acute postoperative pain control for common otolaryngology surgeries.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 498-498
Author(s):  
Prantesh Jain ◽  
Gino Cioffi ◽  
Nirav Patil ◽  
Aman Opneja ◽  
Asrar Alahmadi ◽  
...  

498 Background: Primary liver angiosarcoma (LAS) is a rare and aggressive tumor of the liver. In this analysis of the national cancer database (NCDB) we sought the risk of mortality and factors associated with survival amongst patient diagnosed with LAS. Methods: Patients diagnosed with hepatocellular carcinoma (HCC) or LAS from 2004 – 2014 were identified in the NCDB. The Kaplan-Meier method with the log-rank test was used to calculate survival for HCC and LAS patients. Additional analyses were performed on the cohort with LAS to assess the impact of surgery, chemotherapy, radiation therapy (RT) and facility type on overall survival (OS). Multivariable analyses using cox proportional methods, adjusted for age, sex, Charlson/Deyo score, race, ethnicity, insurance status, facility location and type, surgery status, and chemotherapy status were performed to obtain adjusted hazard ratio (aHR). Results: Total of 118,066 patients with HCC and 346 patients with LAS were identified in the database. Median survival for HCC patients was 11.9 months (95% CI: 11.7-12.2) and 2.0 months for LAS patients (95% CI: 1.8 – 2.4). Risk of mortality was higher for patients with LAS compared to those with HCC (aHR (95% CI): 2.23 (1.97 - 2.53), p < .0001). Among the LAS patients, those who received surgery had a median survival of 8.6 months (95% CI: 5.6 - 17.3), and 1.8 months for those who did not (95% CI: 1.48 - 1.94). Risk of mortality was lower in patients who received surgery compared to those who did not (aHR (95% CI): 0.23 (0.15 - 0.37), p < .0001). Patients treated at and academic center had a higher median survival (3.3 months, 95% CI: 2.2 - 4.1) then those treated at a non-academic center (1.5 months, 95% CI: 1.2 - 1.8). Though, there was no significant difference in OS (aHR (95% CI): 0.48 (0.21 - 1.10), p = 0.082). A very small number of patients received chemotherapy or RT to conduct a meaningful analysis. Conclusions: Patients diagnosed with primary LAS have a worse OS compared to those with HCC. Amongst patients with primary LAS, surgical resection is associated with best survival outcomes. Treatment at an academic center is associated with better median survival, although OS did not reach statistical significance in our analysis.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S144-S144
Author(s):  
Azza Elamin ◽  
Faisal Khan ◽  
Ali Abunayla ◽  
Rajasekhar Jagarlamudi ◽  
aditee Dash

Abstract Background As opposed to Staphylococcus. aureus bacteremia, there are no guidelines to recommend repeating blood cultures in Gram-negative bacilli bacteremia (GNB). Several studies have questioned the utility of follow-up blood cultures (FUBCs) in GNB, but the impact of this practice on clinical outcomes is not fully understood. Our aim was to study the practice of obtaining FUBCs in GNB at our institution and to assess it’s impact on clinical outcomes. Methods We conducted a retrospective, single-center study of adult patients, ≥ 18 years of age admitted with GNB between January 2017 and December 2018. We aimed to compare clinical outcomes in those with and without FUBCs. Data collected included demographics, comorbidities, presumed source of bacteremia and need for intensive care unit (ICU) admission. Presence of fever, hypotension /shock and white blood cell (WBC) count on the day of FUBC was recorded. The primary objective was to compare 30-day mortality between the two groups. Secondary objectives were to compare differences in 30-day readmission rate, hospital length of stay (LOS) and duration of antibiotic treatment. Mean and standard deviation were used for continuous variables, frequency and proportion were used for categorical variables. P-value &lt; 0.05 was defined as statistically significant. Results 482 patients were included, and of these, 321 (67%) had FUBCs. 96% of FUBCs were negative and 2.8% had persistent bacteremia. There was no significant difference in 30-day mortality between those with and without FUBCs (2.9% and 2.7% respectively), or in 30-day readmission rate (21.4% and 23.4% respectively). In patients with FUBCs compared to those without FUBCs, hospital LOS was longer (7 days vs 5 days, P &lt; 0.001), and mean duration of antibiotic treatment was longer (14 days vs 11 days, P &lt; 0.001). A higher number of patients with FUBCs needed ICU care compared to those without FUBCs (41.4% and 25.5% respectively, P &lt; 0.001) Microbiology of index blood culture in those with and without FUBCs Outcomes in those with and without FUBCs FUBCs characteristics Conclusion Obtaining FUBCs in GNB had no impact on 30-day mortality or 30-day readmission rate. It was associated with longer LOS and antibiotic duration. Our findings suggest that FUBCs in GNB are low yield and may not be recommended in all patients. Prospective studies are needed to further examine the utility of this practice in GNB. Disclosures All Authors: No reported disclosures


Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 771-786
Author(s):  
Kerstin Schütte ◽  
Regina Schinner ◽  
Mathias P. Fabritius ◽  
Melina Möller ◽  
Christiane Kuhl ◽  
...  

<b><i>Introduction:</i></b> Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. <b><i>Objective:</i></b> To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). <b><i>Methods:</i></b> SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. <b><i>Results:</i></b> In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, <i>n</i> = 11; adrenal glands, <i>n</i> = 5; peritoneum, <i>n</i> = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (<i>p</i> = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; <i>p</i> = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, <i>p</i> = 0.0060). <b><i>Conclusions:</i></b> This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
R King ◽  
D Giedrimiene

Abstract Funding Acknowledgements Type of funding sources: None. Background The management of patients with multiple comorbidities represents a significant burden on healthcare each year. Despite requiring regular medical care to treat chronic conditions, a large number of these patients may not receive proper care. Significant disparities have been identified in patients with multiple comorbidities and those who experience acute coronary syndrome or acute myocardial infarction (AMI). Only limited data exists to identify the impact of comorbidities and utilization of primary care physician (PCP) services on the development of adverse outcomes, such as AMI. Purpose The primary objective was to analyze how PCP services utilization can be associated with comorbidities in patients who experienced an AMI. Methods This study was based on retrospective data analysis which included 250 patients admitted to the Hartford Hospital Emergency Department (ED) for an AMI. Out of these, 27 patients were excluded due to missing documentation. Collected data included age, gender, medications and recorded comorbidities, such as hypertension, hyperlipidemia, diabetes mellitus (DM), chronic kidney disease (CKD) and previous arrhythmia. Each patient was assessed regarding utilization of PCP services. Statistical analysis was performed in order to identify differences between patients with documented PCP services and those without by using the Chi-square test. Results The records allowed for identification of documented PCP services for 172 out of 223 (77.1%) patients. The most common comorbidities were hypertension and hyperlipidemia: in 165 (74.0%) and 157 (70.4%) cases respectively. The most frequent comorbidity was hypertension: 137 out of 172 (79.7%) in pts with PCP vs 28 out of 51 (54.9%) without PCP, and significantly more often in patients with PCP, p&lt; 0.001. Hyperlipidemia was the second most frequent comorbidity: in 130 out of 172 (75.6%) vs 27 out of 51 (52.9%) accordingly, and also significantly more often (p&lt; 0.002) in patients with PCP services. The number of comorbidities ranged from 0-5, including 32 (14.3%) patients without comorbidities: 16 (9.3%) with a PCP and 16 (31.4%) without PCP services. The majority of patients - 108 (48.5% of 223), had 2-3 documented comorbidities: 89 (51.8%) had two and 19 (34.6%) had three. The remaining 40 (17.9%) patients had 4-5 comorbidities: 37 (21.5%) of them with a PCP and 3 (10.3%) without, with a significant difference (p &lt; 0.001) found for patients with a higher number of comorbidities who utilized PCP services. Conclusions Our study shows that the majority of patients who presented with an AMI had one or more comorbidities. Furthermore, patients who did not utilize PCP services had fewer identified comorbidities. This suggests that there may be a significant number of patients who experienced AMI with undiagnosed comorbidities due to not having access to PCP services.


1994 ◽  
Vol 14 (7) ◽  
pp. 4802-4814
Author(s):  
S D Priebe ◽  
J Westmoreland ◽  
T Nilsson-Tillgren ◽  
M A Resnick

Sequence homology is expected to influence recombination. To further understand mechanisms of recombination and the impact of reduced homology, we examined recombination during transformation between plasmid-borne DNA flanking a double-strand break (DSB) or gap and its chromosomal homolog. Previous reports have concentrated on spontaneous recombination or initiation by undefined lesions. Sequence divergence of approximately 16% reduced transformation frequencies by at least 10-fold. Gene conversion patterns associated with double-strand gap repair of episomal plasmids or with plasmid integration were analyzed by restriction endonuclease mapping and DNA sequencing. For episomal plasmids carrying homeologous DNA, at least one input end was always preserved beyond 10 bp, whereas for plasmids carrying homologous DNA, both input ends were converted beyond 80 bp in 60% of the transformants. The system allowed the recovery of transformants carrying mixtures of recombinant molecules that might arise if heteroduplex DNA--a presumed recombination intermediate--escapes mismatch repair. Gene conversion involving homologous DNAs frequently involved DNA mismatch repair, directed to a broken strand. A mutation in the PMS1 mismatch repair gene significantly increased the fraction of transformants carrying a mixture of plasmids for homologous DNAs, indicating that PMS1 can participate in DSB-initiated recombination. Since nearly all transformants involving homeologous DNAs carried a single recombinant plasmid in both Pms+ and Pms- strains, stable heteroduplex DNA appears less likely than for homologous DNAs. Regardless of homology, gene conversion does not appear to occur by nucleolytic expansion of a DSB to a gap prior to recombination. The results with homeologous DNAs are consistent with a recombinational repair model that we propose does not require the formation of stable heteroduplex DNA but instead involves other homology-dependent interactions that allow recombination-dependent DNA synthesis.


2020 ◽  
Author(s):  
Shun-Ku Lin ◽  
Chien-Tung Wu ◽  
Chia-Jen Liu ◽  
Hui-Jer Chou ◽  
Fu-Yang Ko ◽  
...  

Abstract Background: Large-scale epidemics have changed people’s medical behavior, and patients tend to delay non-urgent medical needs. However, the impact of the pandemic on the use of complementary and alternative medicine remains unknown. Methods: This retrospective study aimed to analyze the changes in the number of traditional Chinese medicine (TCM) patients and examine the epidemic prevention policy during the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the number of TCM patients in Taipei City Hospital from January 2017 to May 2020. We tallied the numbers of patients in each month and compared them with those in the same months last year. We calculated the percentage difference in the number of patients to reveal the impact of the COVID-19 pandemic on TCM utilization. We used the Mann­–Whitney U test to examine whether there was a significant difference in the number of patients during the COVID-19 pandemic. Results: We included a total of 41 months and 1,935,827 patients in this study. During the COVID-19 pandemic, the number of patients decreased significantly, except in February 2020. The numbers of patients during the COVID-19 pandemic had fallen by more than 15% compared with those in the same months last year. March and April had the greatest number of patient losses, with falls of 32.8% and 40%, respectively. TCM patients declined significantly during the COVID-19 pandemic, and mobile medicine provided to rural areas fell considerably. Among all the TCM specialties, pediatrics and traumatology, as well as infertility treatment, witnessed the most significant decline in the number of patients. However, the number of cancer patients has reportedly increased. Conclusions: The COVID-19 pandemic decreased the utilization rate of TCM, especially for mobile healthcare in rural areas. We suggest that the government pay attention to the medical disparity between urban and rural areas, which are affected by the pandemic, as well as allocate adequate resources in areas deprived of medical care.


2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Hannah Elkadi ◽  
Eleanor Dodd ◽  
Theodore Poulton ◽  
William Bolton ◽  
Joshua Burke ◽  
...  

Abstract Aims Despite being the most common surgical procedure, there is wide variation that exists in the management of simple subcutaneous abscesses with no national guideline describing best practice. During the COVID-19 Pandemic national guidelines promoted the use of regional or local anaesthetic (LA) instead of general anaesthesia (GA) to avoid aerosol generating intubation associated with GA. This study aimed to assess the impact of anaesthetic choice in outcomes following incision and drainage of subcutaneous abscesses. Methods Two cohorts of patients undergoing abscess incision and drainage at St. James’ University Hospital Leeds were retrospectively identified over a 14-week period before and after the introduction of the new COVID-19 anaesthetic guidelines. Wound healing surrogate endpoints were used: i) total number of follow up appointments and ii) attendance to healthcare services after 30 days from I&D. Result 133 patients were included. Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%; p &lt; 0.0001) with a significant reduction in wound packing (68.3% vs 87.1%. p=0.00473). Follow up data found no significant difference in the average number of follow-up appointments (7.46 vs 5.11; p = 0.0731) and the number of patients who required ongoing treatment after 30 days (n = 14 vs n = 14, p = 0.921). Conclusion Drainage of simple subcutaneous abscess under 5 cm is safe under local anaesthetic with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient reported measures such as pain management and the health economics of this intervention.


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