Is early-stage pancreatic adenocarcinoma truly early: stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing

BackgroundNeoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT.MethodsUtilizing the National Cancer Data Base (NCDB), patients with cStage I-II PDAC who underwent pancreatoduodenectomy in 2006–2013 were pathologically staged using the AJCC 8th edition and compared by treatment sequencing.ResultsAmong 13,871 patients, 15.3% received NT. Despite higher pre-treatment T-stage (cT2: 71.9% vs. 56.3%, p < 0.001), NT patients had lower rates of pathologic nodal metastases (46.2% vs. 69.2% in SF, p < 0.001), suggesting higher rates of pathologic downstaging. In cStage II, 33.0% were upstaged to stage III after SF, vs. only 14.0% after NT. In cStage I, 65.5% were upstaged following SF, vs. 46.7% after NT (all p < 0.001). Patients with NT (HR-0.77, p < 0.001) or downstaging (HR-0.80, p < 0.001) had improved overall survival (OS).ConclusionNT is associated with reduction in unexpected upstaging, reduction in nodal positivity, and improved OS, compared to SF approach in putatively early-stage PDAC. Because clinical staging underestimates the underlying disease burden in resectable PDAC, patients with cStage I-II should be considered for NT.     

High Systemic Immune-Inflammation Index (SII) Represents an Unfavorable Prognostic Factor for Small Cell Lung Cancer Treated with Etoposide and Platinum-Based Chemotherapy

Purpose

Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with prognosis of a series of solid tumors. However, its role in small cell lung cancer (SCLC) remains poorly understood. The present study aims to evaluate the prognostic significance of pretreatment SII in SCLC treated with etoposide and platinum-based chemotherapy.

Methods

Sixty hundred and fifty-three newly diagnosed SCLC patients were enrolled. The optimal cut-off values for SII and LDH (lactate dehydrogenase) were obtained by a receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed by univariate and multivariate analyses.

Results

The optimal cut-off values of pretreatment SII and LDH were 748.51 × 10⁹/L and 188.5 U/L, respectively. High pretreatment SII was significantly associated with advanced tumor stage (limited disease, LD vs. extensive disease, ED; 26.3% vs 46.5%; p < 0.001). On univariate analysis, age < 65 years, female, non-smoker, limited disease, SII < 748.51 × 10⁹/L, LDH < 188.5 U/L, distant metastasis numbers < 2, chemotherapy + radiotherapy, and chemotherapy + surgery were closely correlated with a prolonged OS (p < 0.05). The median OS for patients in high SII group was 12.0 months, compared with that of 17.0 months for patients in low SII group. Multivariate analysis showed smoking history (p = 0.014), tumor stage (p < 0.001), pretreatment SII (p < 0.001), LDH (p = 0.002), distant metastasis numbers (p = 0.006), and chemotherapy + radiotherapy (p < 0.001) were independent prognostic factors of OS. Furthermore, SII remained prognostic significance for SCLC stratified by variable subgroups analysis.

Conclusion

Pretreatment SII represents a powerful prognostic biomarker for SCLC patients treated with etoposide and platinum-based chemotherapy. It is significant for treatment strategy making in clinics.

     

Perioperative blood transfusion and resection of colorectal cancer liver metastases: outcomes in routine clinical practice

BackgroundPrior work has shown associations between blood transfusion (BT) and inferior outcomes during resection for colorectal cancer liver metastases (CRLM). Herein, we describe short and long-term outcomes relating to perioperative BT in routine clinical practice.MethodsAll CRLM resections in Ontario, Canada from 2002 to 2009 were identified using the Ontario Cancer Registry. Log-binomial regression and Cox regression were used to explore factors associated with receipt of BT and the association of BT with 5-year cancer specific (CSS) and overall survival (OS), respectively.ResultsThe study included 1310 patients; 31% (403/1310) had perioperative BT. Transfused patients had longer median length of stay (9 vs. 7 days, p < 0.001), higher 90-day mortality (9% vs. 1%, p < 0.001), greater 90-day readmission (28% vs. 16%, p < 0.001), and inferior 5-year CSS (41% vs. 48%, p = <0.001) and OS (38% vs. 47%, p < 0.001). Transfusion was independently associated with inferior CSS (HR = 1.35, 95% CI: 1.11–1.63) and OS (HR = 1.30, 95% CI: 1.10–1.53), however, excluding 90-day postoperative deaths showed these associations were no longer significant.ConclusionPerioperative BT is common in patients undergoing resection of CRLM. While transfusion is associated with greater morbidity, mortality, and inferior survival, after excluding early postoperative deaths, BT does not appear to be independently associated with CSS or OS.     

Pathologic complete response following neoadjuvant therapy for pancreatic ductal adenocarcinoma: defining the incidence,predictors, and outcomes

BackgroundNeoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC) but the nationwide incidence and long-term prognosis of a pathologic complete response (pCR) remains poorly understood.MethodsPatients with localized PDAC and known cT and pT stage who received NT prior to pancreatectomy from 2004 to 2016 were identified using the National Cancer Database. The clinicopathologic characteristics and long-term outcomes of patients who did and did not experience a pCR were compared.ResultsAmong 7,902 patients who underwent NT prior to pancreatectomy, 244 (3.1%) experienced a pCR while 7,658 (96.9%) did not. On multivariable regression, longer duration of NT (OR 1.20, 95% CI 1.14–1.27 per month) and use of preoperative radiation (OR 9.98, 95% CI 3.05–32.71) were independently associated with a pCR. Median overall survival (OS) was longer among patients who experienced a pCR (77 vs 26 months, p < 0.001). On multivariate analysis, pCR was the strongest predictor of improved OS (HR 0.43, 95%CI 0.32–0.58, p < 0.001).ConclusionA pCR following NT for PDAC occurs infrequently but is associated with significantly improved OS. Better predictors of response and more effective preoperative regimens should be aggressively sought.     

Haematological response and overall survival in two consecutive Dutch patient cohorts with AL amyloidosis diagnosed between 2008 and 2016

Abstract

Background: Although survival has improved in recent decades, the short-term prognosis of patients with immunoglobulin light chain (AL) amyloidosis remains grim. We aimed to assess overall survival (OS) of AL amyloidosis patients by comparing cohorts in two consecutive time periods.

Methods: Data were collected and compared on 126 patients from two tertiary referral centres in The Netherlands during the time periods 2008–2012 and 2013–2016.

Results: There was a non-significant trend to improved 6-month OS in the last cohort (78% vs. 67%, p?=?.216, crude odds ratio 1.66, 95%CI 0.74–3.70, adjusted odds ratio 2.22, 95%CI 0.88–5.56). Patients in this cohort had higher Mayo risk scores (stage III 40% vs. 24%, p?<?.001 and revised stage IV 14% vs. 11%, p?<?.001), higher use of bortezomib (50% vs. 30%), and better haematological response (complete response/very good partial response in 39% vs. 27%, p?<?.001). Diagnostic delay was similar in both time periods.

Conclusions: In the 2013–2016 cohort there was a trend toward improved 6-month OS, and an improved haematological response. Patients in this cohort had more advanced cardiac disease and received bortezomib more frequently, but diagnostic delay was similar to the 2008–2012 cohort. For further prognostic improvement, practitioners should be more alert, especially for cardiac amyloidosis.     

A comprehensive SEER registry analysis of elderly patients with classical Hodgkin lymphoma based on treatment era and race

We conducted a Surveillance, Epidemiology, and End Results Program (SEER-18) registry analysis of classical Hodgkin lymphoma (cHL) patients more than 60 years old and compared outcomes of those diagnosed between 2006 and 2010 (cohort 1) to those identified between 2011 and 2015 (cohort 2) based on treatment era and race. Cohort 1 had a median overall survival (OS) of 4 years and cohort 2 had a median OS of 4.75 years [hazard ratio (HR): 0.92 (0.85–1.00); p = 0.052]. Non-Hispanic blacks (NHBs) had a similar 5-year OS compared to non-Hispanic whites (NHWs) of 48.6% vs. 50.2% (HR: 0.95 [0.79–1.15]; p > 0.99); on the contrary, Hispanics had worse 5-year OS of 41.8% vs. 48.6% (HR: 1.24 [1.09–1.41]; p < 0.001). NHW was the only race that had improvement in 5-year OS in 2011–2015 compared to 2006–2010 (51% vs. 46.5%, p = 0.002). In the multivariable analysis, older age, male gender, stage III–IV, unmarried status, Hispanic race, lack of chemotherapy, and diagnosis in 2006–2010 were associated with worse OS. Lymphoma was the most common cause of death in 60% of patients. In conclusion, elderly cHL patients diagnosed after 2010 had improved OS by nine months that was most prevalent in NHWs, and disparity in OS existed between NHWs and Hispanics throughout the study period.     

Preoperative level of serum amyloid A is superior to C‐reactive protein in the prognosis of esophageal squamous cell carcinoma

Preoperative elevations in the levels of serum amyloid A (SAA) or C‐reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative‐intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1‐, 3‐, and 5‐year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r² = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.     

Outcomes of young adults (aged ≤ 40 years) with newly diagnosed multiple myeloma after up-front autologous stem cell transplant

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22–40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9–238.0), median PFS and OS were 43.1 months (95% CI 31.2–65.0) and 146.6 months (95% CI 100.0–208.1) respectively. Patients who underwent auto-HCT after 2010 had better median PFS (84.9 months vs. 28.2 months, p < 0.001) and OS (NR vs. 91.8 months, p < 0.001) compared with those transplanted earlier. In multi-variate analysis, achieving ≥CR as best post-transplant response was associated with improved PFS (HR [95% CI] 0.55 [0.32–0.95], p = 0.032), while achieving ≥VGPR was predictive of superior OS (0.32 [0.16–0.62], p < 0.001). Three patients (3%) developed a second primary malignancy. Younger MM patients had durable survival after auto-HCT, which further improved after the availability of novel anti-myeloma drugs in recent years. Depth of response following transplant remains a key predictor of survival.     

Safety,Efficacy, and Long-Term Outcomes of Anticoagulation in Cirrhotic Portal Vein Thrombosis

Background

The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear.

Aims

We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not.

Methods

Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan–Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals.

Results

A total of 214 patients were followed for a median 27 months (IQR 12–48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p?=?0.0007), (multivariable HR for CRR with AC; 2.49 (1.54–4.04, p?=?0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p?=?0.0013), (multivariable HR for RCO with AC; 4.86 (1.91–12.37, p?=?0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p?=?0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68–2.46, p?=?0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p?=?0.1362), (HR for death with AC; 0.69 (0.38–1.28, p?=?0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence).

Conclusions

AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.

     

Impact of anti-centromere antibodies on pulmonary function test results in patients with systemic sclerosis without established or suspected pulmonary disease

Pulmonary arterial hypertension (PAH) occurs in approximately 15 % of patients with systemic sclerosis (SSc). Annual screening with pulmonary function tests (PFT) is recommended to help identify those patients at risk of PAH. We have noted that patients with SSc who carry anti-centromere autoantibodies (ACA) often have PFT abnormalities, in the absence of clinical evidence of PAH. To evaluate this further, we undertook a retrospective case-control study evaluating PFT results in patients with SSc in whom pulmonary complications have neither been diagnosed nor suspected. Patients were divided according to ACA carriage and groups compared for PFT results. The median forced vital capacity (FVC) was higher in ACA-positive patients (106 vs. 93 %, p?=?0.004). The gas transfer factor (TLco) was significantly lower in the ACA group (62.5 vs. 71 %, p?=?0.013). The resulting FVC:TLco was significantly higher for ACA-positive vs. ACA-negative patients with SSc (1.70 vs. 1.29, p?<?0.001). Our findings suggest patients carrying ACA, without established or suspected pulmonary complications, have PFT abnormalities consistent with indolent increased pulmonary vascular resistance despite the majority of such patients not subsequently developing PAH. The long-term sequelae of PFT abnormalities in those patients with ACA who do not subsequently develop PAH are unknown.     

Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study

Background

Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., ‘right-sided colon vs. left-sided colon,’ ‘colon vs. rectum,’ and ‘right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).’ This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum.

Methods

Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined.

Results

Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59–0.72; p < 0.001) and left-sided colon cancer (n = 3910) (HR 0.72; 95% CI 0.66–0.78; p < 0.001) after adjusting for key clinical factors (i.e., sex, age, histological type, CEA, adjuvant therapy, T category, and N category). Among patients with recurrence (n = 2823), rectal cancer was associated with better OS compared to right-sided colon cancer (HR 1.23; 95% CI 1.08–1.40; p = 0.002) and worse OS compared to left-sided colon cancer (HR 0.88; 95% CI 0.79–0.99; p = 0.029). Twenty percent of right-sided colon cancer recurrences exhibited peritoneal dissemination, 42% of left-sided colon cancer recurrences were liver metastases, and 33% of rectal cancer recurrences were local recurrences.

Conclusions

The three tumor locations (right-sided colon, left-sided colon, rectum) had different prognostic implications for recurrence after curative resection and overall mortality, suggesting that tumor location serves as a prognostic biomarker in stage III colorectal cancer.

     

Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR)

Idelalisib (idela), a phosphatidylinositol 3-kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R-idela) versus ibrutinib have been conducted. Therefore, we performed a real-world retrospective analysis of patients with R/R CLL treated with R-idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R-idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression-free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R-idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R-idela in patients with R/R CLL treated in routine practice. The R-idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative.     

New drugs for colorectal cancer (irinotecan, oxaliplatin, raltitrexed) meet expectations in routine practice: a single center's experience before and after their introduction

Background and Aims: Treatment of metastatic colorectal cancer with new drugs (NDs) as oxaliplatin and irinotecan had improved response and survival. In order to check whether the promising achievements of the trials are obtained in routine clinical practice, we have reviewed retrospectively our results for two periods, before (period A: 1993–1995, n=63) and after (period B: 1998–2000 n=103) the introduction of these NDs. Patients characteristics, treatment modalities, survival, and prognostic factors were compared. Patients: There were 74 women and 92 men, aged 60.8 ±11.6 yr, 7 patients received best supportive care only, 91 had synchronous metastasis. Results: Period B patients were older, with WHO score >1 more often, more adjuvant treatment, more metachronous metastasis, and NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo). But when looking at the population aged <75 years with WHO score <2, median survival was 13 mo (period A) vs 21 mo (period B); survival at 1,2, and 3 yr were respectively 59.5±8%, 16.2±6%, 13.5±6% vs 69.8±6%, 49.6±7%, 29.8±7%, p<0.01). In multiparametric analysis, factors correlated with survival were the absence of elevated serum alkaline phosphatase, a unique metastatic organ, and administration of NDs. Conclusion: In our routine clinical experience the use of NDs for metastatic CRC has allowed a significant improvement in survival among patients with unresectable tumors.     

Hodgkin lymphoma post‐transplant lymphoproliferative disorder: A comparative analysis of clinical characteristics,prognosis, and survival

Hodgkin lymphoma post‐transplant lymphoproliferative disorder (HL‐PTLD) is an uncommon PTLD with unclear prognosis and differences between HL‐PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL‐PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL‐SEER). Overall survival (OS) and disease‐specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL‐PTLD diagnosis was 88 months. When compared with HL‐SEER, patients with HL‐PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five‐year OS for patients with HL‐PTLD was 57% versus 80% for HL‐SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL‐PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL‐specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10‐year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL‐PTLD patients have inferior survival when compared with HL‐SEER. Furthermore, treatment with HL‐specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560–565, 2016. © 2016 Wiley Periodicals, Inc.     

Arterial pressure profile in patients with cirrhosis: Fourier analysis of arterial pulse in relation to pressure level,stroke volume,and severity of disease: On the reduction of afterload in the hyperdynamic syndrome

Abstract

Objective. Patients with cirrhosis have cardiovascular dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyze the arterial pressure curve in relation to mean arterial pressure level, stroke volume, and severity of liver disease. Materials and methods. Forty-one patients with cirrhosis (Child–Turcotte classes A/B/C = 13/15/13) were studied during a hemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. We applied fast Fourier analysis to quantify the pressure components of the arterial curve, the harmonic Fourier coefficients (HFC). Results. Mean arterial pressure was significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis versus controls. The HFC were significantly lower in patients with cirrhosis than in controls (–15 to –24%, p < 0.002), except for the fourth HFC, which was significantly increased (+28%, p < 0.02). In contrast to controls, which showed a highly significant effect of the level of arterial pressure on their HFC (p < 0.001), patients with cirrhosis did not show pressure or stroke volume dependence on their HFC, indicating an overall compliant and slow reflective arterial vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to the Child–Turcotte score (p < 0.05), and the HFC were borderline significantly related to this score (p = 0.07). Conclusions. The arterial pulsation in cirrhosis is qualitatively changed with reduced pulse reflections, which may protect against manifest cardiac failure in patients with advanced cirrhosis.     

Different prognosis of patients with esophageal carcinoma with M1a and regional node involvement

Background and purposeBased on the 6th edition of the American Joint Commission on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC), M1a node involvement was classified as regional node involvement in the revised 7th/8th edition. However, the clinical significance of M1a node involvement is unclear. Thus, we analyzed the prognostic value of M1a node involvement in patients with ESCC after definitive concurrent chemoradiotherapy (CCRT).Materials and methodsIn total, 188 patients with ESCC had M0 disease according to the 7th/8th edition AJCC. We reclassified 31 (16.5%) of these patients as having M1a disease according to the 6th edition. After definitive CCRT, we compared baseline characteristics between the two groups and analyzed the rates of responders and recurrence. Finally, we compared prognoses according to overall survival (OS), disease-specific OS, and disease-free survival (DFS).ResultsAmong 31 patients reclassified to have M1a disease, 21 (67.7%) had supraclavicular lymph node metastasis and 10 (32.3%) had celiac lymph node metastasis. The number of responders was significantly lower for M1a disease based on univariate (p = 0.004) and multivariate (p = 0.011) analyses. Significantly lower survival rates were observed in individuals with M1a disease (median OS, 16.4 vs. 42.7 months; 5-year OS, 10.8% vs. 41.2%).ConclusionsM1a node involvement should be differentiated from regional node involvement.     

Comparison of adherence,persistence, and clinical outcome of generic and brand-name statin users: A retrospective cohort study using the Japanese claims database

BackgroundNon-adherence to statin treatment results in an increased risk of cardiovascular events and all-cause mortality. This study compared adherence, persistence, and clinical outcomes of patients who initiated brand-name and generic statins in the Japanese population.MethodsThe retrospective cohort study included adult patients who initiated statins between 2014 and 2016. Primary adherence was measured as the proportion of days covered (PDC) within 1 year. Persistence was assessed using the proportion of non-persistent users. Any major adverse cardiac and cerebrovascular event (MACCE) was assessed as a clinical outcome. Propensity score matching was performed to adjust for confounding factors.ResultsAmong 47,770 patients who met inclusion criteria in the study, 32,130 (67.3%) initiated generic statins. The median age of the patients was 53 (interquartile range: 46-59) years and 60.2% were male. A higher proportion of patients with PDC ≥80% [60.2% vs. 57.1%; odds ratio, 1.14; 95% confidence interval (CI), 1.09–1.19; p<0.001] and a higher PDC value (median, 90.2% vs. 87.9%; difference, 2.3%; p<0.001) were observed in the generic group. Similarly, fewer patients discontinued statins in the generic group [24.2% vs. 27.7%; hazard ratio (HR), 0.91; 95% CI, 0.87–0.95; p<0.001]. Differences in MACCE occurrence were not significant between the groups (4.3% vs. 4.2%; HR, 1.04; 95% CI, 0.93–1.17; p=0.99).ConclusionsAdherence and persistence were higher among generic statin recipients; nevertheless, no significant differences in clinical outcomes were noted between the two groups, suggesting that generic medication did not impair treatment benefits and may improve patient adherence.     

Clinical characteristics,molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Methods: We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002–2015).

Results: MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n?=?19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n?=?12), 35% for CD68 (n?=?8), 30% for CD34 (n?=?7), and 26% for lysozyme (n?=?6). Cytogenetic abnormalities were seen in 63% (n?=?12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n?=?3) or monosomal (n?=?2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4–24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p?=?0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p?Conclusion: Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.     

Applicability of the PAINESD risk score for 30-day mortality prediction post ventricular tachycardia catheter ablation in Chagas disease

Background

Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is standard of care. However, it is underutilized. In July 2012, our institution began providing cell phone adapters (CPAs) to patients free of charge following CIED implantation to improve remote transmission (RT) adherence.

Methods

Patients in our institution’s RM database from January 1, 2010, thru June 30, 2015, were retrospectively reviewed. There were 2157 eligible patients. Remote transmission proportion (RTP) and time to transmission (TT) were compared pre- and post-implementation of free CPA. Chi-squared analysis and Kruskal-Wallis tests were performed to compare RTP and TT.

Results

There was a significant increase in RTP (134 [18.4%] vs 99 [54.7%]; p?<?0.001) and decrease in median TT in days (189[110–279] vs 58 [10–149]; p?<?0.001) after CPAs were provided to patients. Caucasian patients were more likely than African Americans and Hispanics to use RM prior to CPAs (p?=?0.04). After the implementation of CPAs, there was a significant increase in RTP for all racial groups (<?0.001) with no difference in RTP among racial groups (p?=?0.18). The RTP for urban residents was significantly greater than non-urban residents with CPAs (p?=?0.008). Patients greater than 70 years of age were significantly less likely to participate in RT before and after CPAs were provided (p?=?0.03, p?=?0.01, respectively).

Conclusions

CPAs significantly improve RTP and reduce median TT for all patients regardless of race, geographic residence, and age (>?70 years old to lesser extent). Broad institution of CPAs following ICD implantation could potentially reduce disparity in RTP and deserves more study.

     

Bone marrow plasma cell infiltration in light chain amyloidosis: impact on organ involvement and outcome

Abstract

Objectives: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis.

Methods: The clinical records of 79 patients with AL amyloidosis treated at a single institution.

Results: Median BMPC infiltration at diagnosis was 11% and significantly correlated with the serum free light-chain difference (p?<?.001). Patients with more than 10% BMPCs had more frequent cardiac involvement (86 vs. 63%; p?=?.015), a trend towards a higher early mortality (27 vs. 11%; p?=?.08) and a significantly shorter progression-free survival (PFS) (median of 18 vs. 48?months, p?=?.02) and overall survival (median of 33?months vs. not reached; p?=?.046). In the multivariate analysis, a BMPC infiltration over 10% retained its adverse prognostic value for PFS (HR?=?2.26; 95% CI, 1.048–4.866; p?=?.038). The use of new drugs seemed to overcome the negative prognostic impact of a higher BMPC infiltration.

Conclusion: Higher BMPC infiltration in AL amyloidosis might be associated with increased systemic organ damage, particularly cardiac involvement and is rarely related to the development of myeloma features.