ResearchPad - retrospective-study https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care]]> https://www.researchpad.co/article/elastic_article_13954 Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIMTo define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODSAll patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012–2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSIONDespite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered. ]]> <![CDATA[Optimal proximal resection margin distance for gastrectomy in advanced gastric cancer]]> https://www.researchpad.co/article/elastic_article_13925 The conventional guidelines to obtain a safe proximal resection margin (PRM) of 5-6 cm during advanced gastric cancer (AGC) surgery are still applied by many surgeons across the world. Several recent studies have raised questions regarding the need for such extensive resection, but without reaching consensus. This study was designed to prove that the PRM distance does not affect the prognosis of patients who undergo gastrectomy for AGC.AIMTo investigate the influence of the PRM distance on the prognosis of patients who underwent gastrectomy for AGC.METHODSElectronic medical records of 1518 patients who underwent curative gastrectomy for AGC between June 2004 and December 2007 at Asan Medical Center, a tertiary care center in Korea, were reviewed retrospectively for the study. The demographics and clinicopathologic outcomes were compared between patients who underwent surgery with different PRM distances using one-way ANOVA and Fisher’s exact test for continuous and categorical variables, respectively. The influence of PRM on recurrence-free survival and overall survival were analyzed using Kaplan-Meier survival analysis and Cox proportional hazard analysis.RESULTSThe median PRM distance was 4.8 cm and 3.5 cm in the distal gastrectomy (DG) and total gastrectomy (TG) groups, respectively. Patient cohorts in the DG and TG groups were subdivided into different groups according to the PRM distance; ≤ 1.0 cm, 1.1-3.0 cm, 3.1-5.0 cm and > 5.0 cm. The DG and TG groups showed no statistical difference in recurrence rate (23.5% vs 30.6% vs 24.0% vs 24.7%, P = 0.765) or local recurrence rate (5.9% vs 6.5% vs 8.4% vs 6.2%, P = 0.727) according to the distance of PRM. In both groups, Kalpan-Meier analysis showed no statistical difference in recurrence-free survival (P = 0.467 in DG group; P = 0.155 in TG group) or overall survival (P = 0.503 in DG group; P = 0.155 in TG group) according to the PRM distance. Multivariate analysis using Cox proportional hazard model revealed that in both groups, there was no significant difference in recurrence-free survival according to the PRM distance.CONCLUSIONThe distance of PRM is not a prognostic factor for patients who undergo curative gastrectomy for AGC. ]]> <![CDATA[Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation]]> https://www.researchpad.co/article/Nc3395340-6a24-4902-b8c0-6eecc876f67b Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIMTo assess the impact of pre-transplant iron metabolism parameters on post-transplant survival.METHODSFrom 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.RESULTSAt the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)].CONCLUSIONOur results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study. ]]> <![CDATA[Pediatric living donor liver transplantation decade progress in Shanghai: Characteristics and risks factors of mortality]]> https://www.researchpad.co/article/N3379f5c8-b807-41e1-9acf-5d05c5e1a62f

BACKGROUND

Pediatric living donor liver transplantation (LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, surgical and anesthesia techniques, the survival rates and long-term outcomes of patients after LDLT have significantly improved worldwide. However, data on anesthetic management and postoperative survival rate of pediatric LDLT in China are rare.

AIM

To review the status of pediatric LDLT in Shanghai and investigate the factors related to anesthetic management and survival rate in pediatric LDLT.

METHODS

We conducted a retrospective observational study to investigate the status of pediatric LDLT in Shanghai by reviewing 544 records of patients who underwent pediatric LDLT since the first operation on October 21, 2006 until August 10, 2016 at Renji Hospital and Huashan Hospital.

RESULTS

The 30-d, 90-d, 1-year, and 2-year survival rates were 95.22%, 93.38%, 91.36%, and 89.34%, respectively. The 2-year patient survival rate after January 1, 2011 significantly improved compared with the previous period (74.47% vs 90.74%; hazard ratio: 2.92; 95% confidence interval (CI): 2.16–14.14; P = 0.0004). Median duration of mechanical ventilation in the intensive care unit (ICU) was 18 h [interquartile range (IQR), 15.25–20.25], median ICU length of stay was 6 d (IQR: 4.80–9.00), and median postoperative length of stay was 24 d (IQR: 18.00–34.00). Forty-seven (8.60%) of 544 patients did not receive red blood cell transfusion during the operation.

CONCLUSION

Pediatric end-stage liver disease (PELD) score, anesthesia duration, operation duration, intraoperative blood loss, and ICU length of stay were independent predictive factors of in-hospital patient survival. Pediatric end-stage liver disease score, operation duration, and ICU length of stay were independent predictive factors of 1-year and 3-year patient survival.

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<![CDATA[Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation: Results from a retrospective study on 38 Chinese patients]]> https://www.researchpad.co/article/Nb7b95e07-7202-4487-905e-185a593376ac

BACKGROUND

Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. Some patients have steroid-refractory (SR) GVHD.

AIM

To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.

METHODS

We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered 5-10 mg/d depending on disease severity, patient status, and the use of anti-fungal drugs. Overall response rate, time to best response, malignancy relapse rate, infection rate, and treatment-related adverse events were assessed.

RESULTS

The analysis included 10 patients with SR-aGVHD (grade III/IV, n = 9) and 28 patients with SR-cGVHD (moderate/severe, n = 24). For the SR-aGVHD and SR-cGVHD groups, respectively: Median number of previous GVHD therapies was 2 (range: 1-3) and 2 (1-4); median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo; median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo; and overall response rate was 100% (complete response: 80%) and 82.1% (complete response: 10.7%) with a response observed in all GVHD-affected organs. The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0% and 10.7%, respectively. Reactivation rates for cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus, respectively, were 30.0%, 10.0%, and 0% for the SR-aGVHD group and 0%, 14.3%, and 7.1% for the SR-cGVHD group.

CONCLUSION

Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

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<![CDATA[Clinical course of percutaneous cholecystostomies: A cross-sectional study]]> https://www.researchpad.co/article/Na63215d4-2877-4615-86d6-10a3a46d41bd

BACKGROUND

Although cholecystectomy is the standard treatment modality, it has been shown that perioperative mortality is approaching 19% in critical and elderly patients. Percutaneous cholecystostomy (PC) can be considered as a safer option with a significantly lower complication rate in these patients.

AIM

To assess the clinical course of acute cholecystitis (AC) in patients we treated with PC.

METHODS

The study included 82 patients with Grade I, II or III AC according to the Tokyo Guidelines 2018 (TG18) and treated with PC. The patients’ demographic and clinical features, laboratory parameters, and radiological findings were retrospectively obtained from their medical records.

RESULTS

Eighty-two patients, 45 (54.9%) were male, and the median age was 76 (35-98) years. According to TG18, 25 patients (30.5%) had Grade I, 34 (41.5%) Grade II, and 23 (28%) Grade III AC. The American Society of Anesthesiologists (ASA) physical status score was III or more in 78 patients (95.1%). The patients, who had been treated with PC, were divided into two groups: discharged patients and those who died in hospital. The groups statistically significantly differed only concerning the ASA score (P = 0.0001) and WBCC (P = 0.025). Two months after discharge, two patients (3%) were readmitted with AC, and the intervention was repeated. Nine of the discharged patients (13.6%) underwent interval open cholecystectomy or laparoscopic cholecystectomy (8/1) within six to eight weeks after PC. The median follow-up time of these patients was 128 (12-365) wk, and their median lifetime was 36 (1-332) wk.

CONCLUSION

For high clinical success in AC treatment, PC is recommended for high-risk patients with moderate-severe AC according to TG18, elderly patients, and especially those with ASA scores of ≥ III. According to our results, PC, a safe, effective and minimally invasive treatment, should be preferred in cases suffering from AC with high risk of mortality associated with cholecystectomy.

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<![CDATA[Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure]]> https://www.researchpad.co/article/Nbb501aa5-1812-4762-8842-367849eeb2de

BACKGROUND

Acute-on-chronic liver failure (ACLF), which includes hepatic and multiple extra-hepatic organ failure, is a severe emergency condition that has high mortality. ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation. Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.

AIM

To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B (COSSH).

METHODS

A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016. The characteristics of BIs, the 28-d transplant-free survival rates, and the independent predictors of the 28-d outcomes were evaluated.

RESULTS

A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF. Among the episodes, 13.4% were community-acquired, 46.4% were healthcare-associated, and 40.2% belonged to nosocomial BIs. Pneumonia (40.7%), spontaneous bacterial peritonitis (SBP) (34.5%), and bloodstream infection (BSI) (13.4%) were the most prevalent. As the ACLF grade increased, the incidence of SBP showed a downward trend (P = 0.021). Sixty-one strains of bacteria, including 83.6% Gram-negative bacteria and 29.5% multidrug-resistant organisms, were cultivated from 50 patients with ACLF. Escherichia coli (44.3%) and Klebsiella pneumoniae (23.0%) were the most common bacteria. As the ACLF grade increased, the 28-d transplant-free survival rates showed a downward trend (ACLF-1, 55.7%; ACLF-2, 29.3%; ACLF-3, 5.4%; P < 0.001). The independent predictors of the 28-d outcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio [HR] = 1.371), acute kidney injury (HR = 2.187), BSI (HR = 2.339), prothrombin activity (HR = 0.967), and invasive catheterization (HR = 2.173).

CONCLUSION

For patients with HBV-ACLF combined with first BIs, pneumonia is the most common form, and the incidence of SBP decreases with increasing ACLF grade. COSSH-ACLF score, acute kidney injury, BSI, prothrombin activity, and invasive catheterization are the independent predictors of 28-d outcomes.

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<![CDATA[Application of hybrid operating rooms for treating spinal dural arteriovenous fistula]]> https://www.researchpad.co/article/Neaba77e3-b509-45ab-9014-f0d9438e295a

BACKGROUND

A hybrid operating room (hybrid-OR) is a surgical space that combines a conventional operating room with advanced medical imaging devices.

AIM

To explore and summarize the technical features and effectiveness of the application of a hybrid-OR in dealing with spinal dural arteriovenous fistulas (SDAVFs).

METHODS

Eleven patients with SDAVFs were treated with the use of a hybrid-OR at the Department of Neurosurgery of our hospital between January 2015 and December 2018. The dual-marker localization technique was used in the hybrid-OR to locate the SDAVFs and skin incision, and the interoperative digital subtraction angiography (DSA) technique was used before and after microsurgical ligation of the fistulae in the hybrid-OR to verify the accuracy of obliteration. The patients were followed for an average of 2 years after the operation, and the preoperative American Spinal Cord Injury Association (ASIA) score and postoperative ASIA score at 6 mo after the operation were compared.

RESULTS

The location and skin incision of the SDAVFs were accurately obtained by using the dual-marker localization technique in the hybrid-OR in all patients, and there were no cases that required expansion of the range of the bone window in order to expose the lesions. Intraoperative error obliteration occurred and was identified in two patients by using the intraoperative DSA technique; therefore, the findings provided by the intraoperative DSA system significantly changed the surgical procedure in these two patients. With the assistance of the hybrid-OR, the feeding artery was correctly ligated in all cases, and the intraoperative error obliteration rate decreased from 18.2% (2/11) to 0%. All 11 patients were followed for an average of 2 years. The ASIA score at 6 mo after the operation was significantly improved compared with the preoperative ASIA score, and there were no patients with late recurrence during the follow-up.

CONCLUSION

Compared with intra-arterial embolization for the treatment of SDAVFs, hybrid-ORs can solve the problem of a higher incidence of initial failure and late recurrence. Compared with direct occlusion of SDAVFs in microsurgery, hybrid-ORs can take advantage of the intraoperative DSA system for locating the shunt and verifying the obliteration of fistulae in order to reduce the error obliteration rate. At this point, our experience suggests that the safety and ease of use make hybrid-ORs combined with microsurgery and intraoperative DSA systems an attractive modality for dealing with SDAVFs.

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<![CDATA[Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience]]> https://www.researchpad.co/article/N655aeb56-a748-4eb6-a187-b533ac01657e

BACKGROUND

Pertuzumab is a humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer (MBC) when used in combination with a taxane and Trastuzumab, and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer. There are currently few reports on the pattern of use and value of Pertuzumab in real world settings. Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.

AIM

To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.

METHODS

A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted. Demographic and clinical data were extracted from electronic medical records. Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.

RESULTS

Thirty-one (62.0%) of the fifty (16.4%) patients who received Pertuzumab as first-line therapy. With a median follow-up of 21.5 mo, there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups [51.5 (95%CI: 35.8–60.0) vs 32.9 (95%CI: 28.1–37.5) mo; P = 0.0128]. Two (4.88%) patients in the Pertuzumab group experienced grade 3 (G3) cardiotoxicity. The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group. The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.

CONCLUSION

This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity. However, the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

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<![CDATA[What factors influence patient experience in orthopedic oncology office visits?]]> https://www.researchpad.co/article/N0cab9043-29be-42cb-a7b2-0e024d3d3904

BACKGROUND

Patient satisfaction and reported outcomes are becoming increasingly important in determining the efficacy of clinical care. To date no study has evaluated the patient experience in the orthopedic oncology outpatient setting to determine which factors of the encounter are priorities to the patient.

AIM

To evaluate what factors impact patient experience and report satisfaction in an outpatient orthopedic oncology clinic.

METHODS

Press Ganey® patient surveys from a single outpatient orthopedic oncology clinic at a tertiary care setting were prospectively collected per routine medical care. All orthopedic oncology patients who were seen in clinic and received electronic survey were included. All survey responses were submitted within one month of clinic appointment. IRB approval was obtained to retrospectively collect survey responses from 2015 to 2016. Basic demographic data along with survey category responses were collected and statistically analyzed.

RESULTS

One hundred sixty-two patient surveys were collected. Average patient age was 54.4 years (SD = 16.2 years) and were comprised of 51.2% female and 48.4% male. 64.2% of patients were from in-state. Out of state residents were more likely to recommend both the practice and attending physician. The likelihood to recommend attending physician was positively associated with MD friendliness/courtesy (OR = 14.4, 95%CI: 2.5-84.3), MD confidence (OR = 48.2, 95%CI: 6.2-376.5), MD instructions follow-up care (OR = 2.5, 95%CI: 0.4-17.4), and sensitivity to needs (OR = 16.1, 95%CI: 1-262.5). Clinic operations performed well in the categories of courtesy of staff (76%) and cleanliness (75%) and less well in ease of getting on the phone (49%), information about delays (36%), and wait time (37%).

CONCLUSION

Orthopedic specialties can utilize information from this study to improve care from the patient perspective. Future studies may be directed at how to improve these areas of care which are most valued by the patient.

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<![CDATA[Platelet-albumin-bilirubin score - a predictor of outcome of acute variceal bleeding in patients with cirrhosis]]> https://www.researchpad.co/article/N8d37f331-f6c9-4de0-a67f-66564d871a12

BACKGROUND

The albumin-bilirubin (ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin (PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation.

AIM

To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.

METHODS

The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh (CTP) class, Model of End-stage Liver Disease (MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receiving-operator characteristic curve (AUROC) were calculated for survival and rebleeding.

RESULTS

Mean age was 52.6 years; 1176 were male (77.5%), 69 CTP-A (4.5%), 434 CTP-B (29.2%), 1014 CTP-C (66.8%); 306 PALBI-1 (20.2%), 285 PALBI-2 (18.8%), and 926 PALBI-3 (61.1%). Three hundred and thirty-two patients died during hospitalization (21.9%). Bleeding-related mortality occurred in 11% of CTP-B, 28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively.

CONCLUSION

PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.

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<![CDATA[Radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting liver failure]]> https://www.researchpad.co/article/N82694ad7-bdf6-4c2d-9cda-43296c38fd32

BACKGROUND

Postoperative liver failure is the most severe complication in cirrhotic patients with hepatocellular carcinoma (HCC) after major hepatectomy. Current available clinical indexes predicting postoperative residual liver function are not sufficiently accurate.

AIM

To determine a radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting liver failure in cirrhotic patients with HCC after major hepatectomy.

METHODS

For this retrospective study, a radiomics-based model was developed based on preoperative hepatobiliary phase gadoxetic acid-enhanced magnetic resonance images in 101 patients with HCC between June 2012 and June 2018. Sixty-one radiomic features were extracted from hepatobiliary phase images and selected by the least absolute shrinkage and selection operator method to construct a radiomics signature. A clinical prediction model, and radiomics-based model incorporating significant clinical indexes and radiomics signature were built using multivariable logistic regression analysis. The integrated radiomics-based model was presented as a radiomics nomogram. The performances of clinical prediction model, radiomics signature, and radiomics-based model for predicting post-operative liver failure were determined using receiver operating characteristics curve, calibration curve, and decision curve analyses.

RESULTS

Five radiomics features from hepatobiliary phase images were selected to construct the radiomics signature. The clinical prediction model, radiomics signature, and radiomics-based model incorporating indocyanine green clearance rate at 15 min and radiomics signature showed favorable performance for predicting postoperative liver failure (area under the curve: 0.809-0.894). The radiomics-based model achieved the highest performance for predicting liver failure (area under the curve: 0.894; 95%CI: 0.823-0.964). The integrated discrimination improvement analysis showed a significant improvement in the accuracy of liver failure prediction when radiomics signature was added to the clinical prediction model (integrated discrimination improvement = 0.117, P = 0.002). The calibration curve and an insignificant Hosmer-Lemeshow test statistic (P = 0.841) demonstrated good calibration of the radiomics-based model. The decision curve analysis showed that patients would benefit more from a radiomics-based prediction model than from a clinical prediction model and radiomics signature alone.

CONCLUSION

A radiomics-based model of preoperative gadoxetic acid–enhanced MRI can be used to predict liver failure in cirrhotic patients with HCC after major hepatectomy.

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<![CDATA[Landscape of BRIP1 molecular lesions in gastrointestinal cancers from published genomic studies]]> https://www.researchpad.co/article/N8d73af57-0183-4411-a842-4030618dedaa

BACKGROUND

BRIP1 is a helicase that partners with BRCA1 in the homologous recombination (HR) step in the repair of DNA inter-strand cross-link lesions. It is a rare cause of hereditary ovarian cancer in patients with no mutations of BRCA1 or BRCA2. The role of the protein in other cancers such as gastrointestinal (GI) carcinomas is less well characterized but given its role in DNA repair it could be a candidate tumor suppressor similarly to the two BRCA proteins.

AIM

To analyze the role of helicase BRIP1 (FANCJ) in GI cancers pathogenesis.

METHODS

Publicly available data from genomic studies of esophageal, gastric, pancreatic, cholangiocarcinomas and colorectal cancers were interrogated to unveil the role of BRIP1 in these carcinomas and to discover associations of lesions in BRIP1 with other more common molecular defects in these cancers.

RESULTS

Molecular lesions in BRIP1 were rare (3.6% of all samples) in GI cancers and consisted almost exclusively of mutations and amplifications. Among mutations, 40% were possibly pathogenic according to the OncoKB database. A majority of BRIP1 mutated GI cancers were hyper-mutated due to concomitant mutations in mismatch repair or polymerase ε and δ1 genes. No associations were discovered between amplifications of BRIP1 and any mutated genes. In gastroesophageal cancers BRIP1 amplification commonly co-occurs with ERBB2 amplification.

CONCLUSION

Overall BRIP1 molecular defects do not seem to play a major role in GI cancers whereas mutations frequently occur in hypermutated carcinomas and co-occur with other HR genes mutations. Despite their rarity, BRIP1 defects may present an opportunity for therapeutic interventions similar to other HR defects.

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<![CDATA[Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma]]> https://www.researchpad.co/article/N46cfdd86-7a72-4be0-b261-363583d92805

BACKGROUND

Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence.

AIM

To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC.

METHODS

Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria.

RESULTS

Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs.

CONCLUSION

Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

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<![CDATA[Ipsilateral breast tumor recurrence in early stage breast cancer patients treated with breast conserving surgery and adjuvant radiation therapy: Concordance of biomarkers and tumor location from primary tumor to in-breast tumor recurrence]]> https://www.researchpad.co/article/Nd4bfb3d1-d758-40d3-b4e7-e5c5a8e716fa

BACKGROUND

Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge.

AIM

To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes.

METHODS

Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated.

RESULTS

We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR.

CONCLUSION

Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

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<![CDATA[Predictors of distant metastasis in acinic cell carcinoma of the parotid gland]]> https://www.researchpad.co/article/N75238fb3-3b1b-4b71-b50e-f900982bb3f3

BACKGROUND

AiCC is a primarily indolent disease process. Our aim with this study is to determine characteristics consistent with rapidly progressive AiCC of the parotid gland.

AIM

To report on patients with metastatic lung disease from AiCC and potential correlative factors.

METHODS

Single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017. Univariate analyses were performed.

RESULTS

A total of 55 patients were identified. There were 6 patients (10.9%) with primary AiCC of the parotid gland who developed lung metastases. The mean age at diagnosis for patients with lung metastases was 57.8 years of age, in comparison to 40.2 years for those without metastases (P = 0.064). All 6 of the patients with lung metastases demonstrated gross perineural invasion intraoperatively, in comparison to none of those in the non-lung metastases cohort. Worse disease-free and overall survival were significantly associated with gross perineural invasion, high-grade differentiation, and T4 classification (P < 0.001).

CONCLUSION

AiCC of the parotid gland is viewed as a low-grade neoplasm with good curative outcomes and low likelihood of metastasis. With metastasis, however, it does exhibit a tendency to spread to the lungs. These patients thereby comprise a unique and understudied patient population. In this retrospective study, factors that have been shown to be statistically significant in association with worse disease-free survival and overall survival include presence of gross facial nerve invasion, higher T-classification, and high-grade disease.

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<![CDATA[Post-infantile giant cell hepatitis: A single center’s experience over 25 years]]> https://www.researchpad.co/article/Nbdb1f5c8-51f2-41a5-ad70-8f3c06053041

BACKGROUND

Giant cell hepatitis in the adult population remains very poorly defined with only 100 case reports published in the literature over the last three decades.

AIM

To present our center’s experience in an attempt to learn about the predisposing factors, outcomes and efficacy of proposed therapeutic interventions for giant cell hepatitis.

METHODS

A retrospective chart review was conducted through the electronic records of the University of Pittsburgh Medical Center. We queried 36726 liver biopsy reports from January 1, 1991 to December 6, 2016. Our search yielded 50 patients who were identified as carrying a definite diagnosis of post-infantile giant cell hepatitis (PIGCH) by pathology. The data collected included demographic information, laboratory data (liver function tests, autoimmune markers) and transplant status. In order to better analyze patient characteristics and outcomes, subjects were separated into a non-transplant (native) liver group and a post-liver transplant (allograft) group.

RESULTS

The incidence of PIGCH was approximately 0.14% of all biopsies queried in the 25-year period. The mean age was 48 years with 66% females. Liver function tests were classified as 38.2% cholestatic, 35.3% hepatocellular and 26.5% mixed. Autoimmune hepatitis was found to be the most prevalent predisposing factor leading to PIGCH constituting 32% of cases. Management consisted mainly of immunosuppression, viral targeted therapy, supportive care and in six cases liver transplantations.

CONCLUSION

The diagnosis of PIGCH remains clinically challenging and requires a high index of suspicion as well as a thorough history, physical examination, serological workup and liver biopsy. Treatment of the underlying cause can result in clinical stability in a large number of cases.

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<![CDATA[Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers]]> https://www.researchpad.co/article/N537a070d-fe11-4db2-b393-38effb482612

BACKGROUND

Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report median progression-free survival (PFS) less than 3 mo on second-line therapy. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum, though there is a paucity of data regarding its efficacy in this population.

AIM

To assess the efficacy of FOLFIRI in patients with biliary tract cancers.

METHODS

We retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were collected on patient demographics, BTC subtype, response per RECIST v1.1, progression and survival.

RESULTS

Ninety-eight patients were included of which 74 (75%) had metastatic and 24 (25%) had locally advanced disease at the time of treatment with FOLFIRI. The median age was 60 (range, 22-86) years. The number of patients with extrahepatic cholangiocarcinoma, gall bladder cancer and intrahepatic cholangiocarcinoma were 10, 17 and 71, respectively. FOLFIRI was used as 1st, 2nd, 3rd or 4th – Nth lines in 8, 50, 36 and 4 patients, respectively. Median duration on FOLFIRI in the entire cohort was 2.2 (range, 0.5-8.4) mo. The median PFS and overall survival were 2.4 (95% confidence interval (CI): 1.7-3.1) and 6.6 (95%CI: 4.7-8.4) mo, respectively. Median PFS for patients treated with FOLFIRI in 1st, 2nd, 3rd or 4th – Nth lines were 3.1, 2.5, 2.3 and 1.5 mo, respectively. Eighteen patients received concurrent bevacizumab (n = 13) or EGFR-targeted therapy (n = 5) with FOLFIRI, with a median PFS of 2.7 mo (95%CI: 1.7-5.1).

CONCLUSION

In this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI, efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens.

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<![CDATA[Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages I and II gastric cancer]]> https://www.researchpad.co/article/N66a24eea-ca5e-4062-aa89-b31bed8170b7

BACKGROUND

Primary gastric adenosquamous carcinoma (ASC) is an exceedingly rare histological subtype. Gastric signet ring cell carcinoma (SRC) is a unique subtype with distinct tumor biology and clinical features. The prognosis of gastric ASC vs SRC has not been well established to date. We hypothesized that further knowledge about these distinct cancers would improve the clinical management of such patients.

AIM

To investigate the clinicopathological characteristics and prognosis of gastric ASC vs SRC.

METHODS

A cohort of gastric cancer patients was retrospectively collected from the Surveillance, epidemiology, and end results program database. The 1:4 propensity score matching was performed among this cohort. The clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive statistics. Kaplan-Meier method was utilized to calculate the median survival of the two groups of patients. Cox proportional hazard regression models were used to identify prognostic factors.

RESULTS

Totally 6063 patients with gastric ASC or SRC were identified. A cohort of 465 patients was recruited to the matched population, including 370 patients with SRC and 95 patients with ASC. Gastric ASC showed an inferior prognosis to SRC after propensity score matching. In the post-matching cohort, the median cancer specific survival was 13.0 (9.7-16.3) mo in the ASC group vs 20.0 (15.7-24.3) mo in the SRC group, and the median overall survival had a similar trend (P < 0.05). ASC and higher tumor-node-metastasis stage were independently associated with a poor survival, while radiotherapy and surgery were independent protective factors for improved prognosis. Subgroup survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II patients.

CONCLUSION

ASC may have an inferior prognosis to SRC in patients with stages I and II gastric cancer. Our study supports radiotherapy and surgery for the future management of this clinically rare entity.

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<![CDATA[Efficacy of mucosa-submucosa clip closure method after gastric endoscopic submucosal dissection]]> https://www.researchpad.co/article/Nbb471a1a-d2e0-4917-86ea-a21ee3abca4e

BACKGROUND

We recently developed a new endoscopic closure technique using only conventional endo-clips for colorectal lesions. Little is known about the feasibility of the endoscopic mucosa-submucosa clip closure method for gastric lesions.

AIM

To elucidate the efficacy of the endoscopic mucosa-submucosa clip closure method after gastric endoscopic submucosal dissection (ESD).

METHODS

Twenty-two patients who underwent gastric ESD and mucosa-submucosa clip closure were included in this study. In this method, endo-clips are placed at the edges of a mucosal defect. Additional endo-clips are then applied in the same way to facilitate reduction of the defect size. Additional endo-clips are applied to both sides of the mucosal defect. Complete closure can be achieved. We have also developed a “location score” and “closure difficulty index” for assessment purposes.

RESULTS

Complete closure was achieved in 68.2% of the patients (15/22). The location score in the failure group was significantly larger than that in the complete closure group (P = 0.023). The closure difficulty index in the failure group was significantly higher than that in the complete closure group (P = 0.007). When the cutoff value of the closure difficulty index was set at 99, the high closure difficulty index predicted failure with a sensitivity of 57.1%, specificity of 100%, and accuracy of 86.3%.

CONCLUSION

The endoscopic mucosa-submucosa clip closure method was unreliable after gastric ESD, especially in cases with a high closure difficulty index.

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