Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention.

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.

Characteristics of Patients with Cancer Readmitted Within 30 Days to an Acute Palliative Care Unit.

OBJECTIVE(S): For patients with cancer, the emergence of acute palliative care units (APCU) may hold promise in curtailing hospital readmissions. The study aims to describe the characteristics of patients readmitted to an APCU. METHODS: This retrospective study examined patients with cancer readmitted within 30 days to an APCU. Readmissions were further classified as either potentially preventable or non-preventable. RESULTS: Out of 734 discharges from July 1, 2014 to July 1, 2015, 69 (9%) readmissions were identified and analyzed. For index admissions, median length of stay was five days, and one (1%) was discharged home with hospice care. For readmissions, median time from index admission to readmission was nine days, median length of stay was six days, three (4%) patients died, and 20 (30%) went home with hospice. Ten (14.5%) readmissions were deemed potentially preventable (95% CI 7.2-25.0%). Race/ethnicity-White/Black/Hispanic/Others-was 60%, 10%, 20% and 10%, respectively, among potentially preventable readmissions and 76%, 22%, 2% and 0%, respectively, among potentially non-preventable readmissions (P = .012). Potentially preventable readmissions were more likely to have venous thromboembolism (40% vs. 12%, P = .046) and more reasons for readmission (median 2 vs. 1, P = .019). CONCLUSIONS: Among patients with cancer readmitted to an APCU, one out of seven was potentially preventable and a far larger proportion was discharged with hospice care compared to the index admission. Recognition of disease course, meaningful goals of care discussions and timely transition to hospice care may reduce rehospitalization in this population.

Pain or fatigue: which correlates more with suffering in hospitalized cancer patients?

BACKGROUND: The association of pain and suffering seems intuitive, but evidence substantiating this association is lacking. In studies of cancer patients, fatigue, rather than pain, is the most prevalent and debilitating symptom. This study aimed to compare the correlation of pain and fatigue to suffering, and identify other potential sources of suffering in cancer patients treated in a palliative care unit. METHODS: One hundred fifty cancer patients were surveyed. Fifteen variables were measured on a 0- to 10-point scale: suffering, pain, level of acceptable pain, effect of pain on quality of life, fatigue, level of acceptable fatigue, effect of fatigue on quality of life, and specific types of suffering. Univariable associations with suffering were made with Pearson correlation (continuous variables) or t test (binary predictors). Multivariable associations with suffering were assessed with linear regression analysis and bootstrapping. RESULTS: In multivariable analysis, highest pain (parameter estimate 0.38) had a greater impact on suffering than highest fatigue (parameter estimate 0.21). When other variables were assessed, 38% of the variability in suffering was accounted for by pain "now", fatigue in the past 24 hours, and age. CONCLUSION: The most important predictors of greater suffering in hospitalized cancer patients are pain, younger age, and fatigue. Despite their significant effect on suffering, other underlying contributors to suffering have yet to be identified. Designing interventions to reduce fatigue, in addition to pain management, may help in alleviating overall suffering.

Influence of major histocompatibility complex class I chain-related gene A polymorphisms on cytomegalovirus disease after allogeneic hematopoietic cell transplantation.

OBJECTIVE/BACKGROUND: Cytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT. METHODS: We conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity. RESULTS: In multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00-1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83-2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor-recipient mismatch (HR = 1.05; 95% 95% CI, 0.66-1.68; p = .83 and HR = 0.94; 95% CI, 0.51-1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79-1.31; p = .89 and HR = 0.89; 95% CI, 0.65-1.22; p = .47, respectively). CONCLUSION: These findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.

Therapeutic Dose Monitoring of Busulfan Is Associated with Reduced Risk of Relapse in Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Optimal administration of busulfan (Bu) is hampered by variable and unpredictable drug metabolism in individual patients. At our institution, Bu was previously administered with fixed weight-based dosing (WBD) in combination with cyclophosphamide (Cy) and etoposide (E) for patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). In 2014, we adopted real-time pharmacokinetic (PK)-guided therapeutic drug monitoring (TDM) of Bu for all NHL patients undergoing Bu-containing ASCT. Here we compare outcomes of NHL patients who underwent ASCT with Bu/Cy/E using WBD and those who did so using TDM of Bu. We studied 336 consecutive adult NHL patients who underwent ASCT with Bu/Cy/E using WBD from January 2007 to December 2013 (n = 258) or TDM from May 2014 to December 2017 (n = 78), excluding patients with mantle cell lymphoma. Clinical outcomes, including relapse, nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), hepatotoxicity and pulmonary toxicity were compared in the 2 groups. To adjust for differences in baseline characteristics between the groups, propensity-matched cohorts of WBD and TDM patients were also studied. After the first dose of Bu, the dose was increased in 36% of the patients and decreased in 41%. Changes in pulmonary and liver function from baseline to transplantation were not different between the 2 groups, although these changes showed significantly less variability with TDM than with WBD. Relapse was significantly lower and PFS was improved with TDM; 2-year estimates were 19% for TDM and 38% for WBD for relapse (P = .004) and 69% and 55%, respectively, for PFS (P = .038). No significant between-group differences in NRM or OS were seen. In multivariable analysis, TDM remained prognostic for lower risk of relapse (hazard ratio [HR], .52; 95% confidence interval [CI], .30 to .89; P = .018), but did not remain prognostic for PFS (HR, .74; 95% CI, .48 to 1.16; P = .19). Propensity-matched cohorts displayed similar patterns of outcomes. In subset analysis based on disease status at ASCT, TDM was associated with less relapse and better PFS than WBD for patients who underwent transplantation in less than complete remission (CR) compared with those who underwent transplantation in CR. Compared with WBD, PK-directed TDM of Bu reduces the incidence of relapse when used in combination with Cy and E for patients with NHL undergoing ASCT, particularly for patients in less than CR. These data support the continued use of personalized PK-guided dosing for all NHL patients undergoing ASCT with Bu-containing preparative regimens.

Breath analysis in gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Volatile organic compounds (VOCs) are generated during pathologic processes, and their assessment can be used to diagnose and monitor a variety of diseases. Given the role of the microbiome in graft-versus-host disease (GVHD), we hypothesized that microorganisms producing volatile metabolites may alter VOCs expelled in breath in patients with gastrointestinal (GI) GVHD. In this pilot study, exhaled breath samples were obtained from 19 patients with grade 2 to 4 acute GI GVHD, 10 patients with no GVHD at day 100, and 10 healthy control subjects; the samples were analyzed by using mass spectrometry. Overall, nine (47%) patients had grade 2 GVHD, eight (42%) patients had grade 3 GVHD, and two (11%) patients had grade 4 GVHD; 26% had upper GI, 21% had lower GI, and 53% had both upper and lower GI manifestations. Stepwise canonical discriminant analysis identified 5 VOCs distinguishing patients with and without GI GVHD: 2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene (Wilks' Λ, 0.43; F statistic, 6.08; P = .001). The model correctly classified 89% (17 of 19) and 90% (9 of 10) of patients with and without GI GVHD, respectively. Breath analysis is a feasible and promising noninvasive method to detect acute GI GVHD. Further study of serial breath analysis and the gut microbiome in a larger cohort are ongoing to validate these findings.

Effect of bone marrow CD34+cells and T-cell subsets on clinical outcomes after myeloablative allogeneic hematopoietic cell transplantation.

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses. Most patients received busulfan-cyclophosphamide or etoposide-total body irradiation conditioning for acute leukemia or myelodysplastic syndrome. Calcineurin inhibitor-mycophenolate mofetil (CNI-MMF) (49%) or calcineurin inhibitor-methotrexate (CNI-MTX) (47%) were used for GvHD prophylaxis. In multivariable analysis, higher CD34+ dose was associated with platelet engraftment (P < 0.001) and lymphocyte recovery (P = 0.006). There was no association of donor cell subsets with donor chimerism or overall survival. In conclusion, BM graft composition is associated with myeloablative allogeneic HCT outcomes and future studies to evaluate optimal graft composition are needed.

Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. PATIENTS AND METHODS: A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. RESULTS: Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). CONCLUSION: Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option.

Prognostic Factors for Mortality among Day +100 Survivors after Allogeneic Hematopoietic Cell Transplantation.

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation. The majority underwent a myeloablative transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all-cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55; P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the first 100 days were associated with increased risk of ACM. Patients with higher income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells had lower risk of ACM. Our study identifies risk factors for adverse long-term survival in 100-day survivors, a time point when patients frequently are discharged from transplantation centers. In addition to disease- and transplantation-related factors, low socioeconomic status was associated with worse long-term survival, highlighting the need for focused efforts to improve outcomes in vulnerable patient populations.

Community Risk Score for Evaluating Health Care Disparities in Hematopoietic Cell Transplantation.

There is a critical need for tools to comprehensively describe disparities in hematopoietic cell transplant (HCT) recipients. We conducted a retrospective cohort study to evaluate a Community Risk Score (CRS) tool for this purpose. CRS included 10 community health indicators based on county or state of residence obtained from several secondary data sources and a composite score was assigned to each county (range 0 to 40), that was further categorized into six tiers (I to VI) with higher tiers indicating poor community health. CRS was assessed for 509 allogeneic and 1033 autologous HCT recipients from 2003 to 2013. Our cohort represented allogeneic and autologous HCT recipients from 300 and 431 unique ZIP codes from 99 and 125 counties in 15 and 16 states, although 86% and 90% patients were from Ohio, respectively. A greater proportion of patients had adverse individual community risk indicators in higher-risk tiers (P < .001 for trend for all). In multivariable analysis, clear trends toward association of CRS with outcomes were not observed. For autologous HCTs, Tier III has higher risks of relapse mortality (hazard ratio [HR] 2.2, P = .02) and all-cause mortality (HR 1.8, P = 0.03). In conclusion, CRS was able to categorize patients into groups representing greater levels of health care disparities. We did not see a clear association between CRS and transplant outcomes, although our cohort was limited to a relatively small group of counties. Community-based risk score model may serve as a tool for evaluating disparities in HCT recipients, but its validation in a nationally representative cohort of patients is needed.

Efficacy of Standard Dose R-CHOP Alternating With R-HDAC Followed by Autologous Hematopoietic Cell Transplantation as Initial Therapy of Mantle Cell Lymphoma, a Single-Institution Experience.

BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC. We herein report our experience with 28 patients treated with this regimen who proceeded to AHCT, and compare their outcomes with patients treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate, and cytarabine; n = 21), before AHCT. RESULTS: With a median follow-up duration of 26 months, our data show that this modification of the Nordic regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year progression-free and overall survival rates of 69% and 75%, respectively). CONCLUSION: By using a less intense induction, this regimen can serve as a platform for combined use of novel agents, with less risk of additive toxicity.

Analysis of Origins of Admission for Solid Tumor Oncology Inpatients: Disease Severity and Outcomes.

PURPOSE: Hospital transfers may affect clinical outcomes. Evaluation of admission by source of transfer, time of admission, and provider type may identify opportunities to improve inpatient outcomes. METHODS: We reviewed charts of patients admitted to the solid tumor oncology service between July and December 2014 from the Cleveland Clinic Foundation (CCF) Main Campus emergency department (ED), CCF Regional EDs, outside hospital (OSH) ED, OSH inpatient services, and CCF outpatient clinics. Data collected included time of admission, mortality and severity risk scores, and provider type. Risk factors were assessed for clinical outcomes, including activations of the Adult Medical Emergency Team, intensive care unit transfers, in-hospital mortality, and length of stay (LOS). RESULTS: Five hundred admissions were included. OSH inpatient transfers had significantly higher disease severity compared with all other origins of admission. OSH inpatient transfers demonstrated significantly longer LOS compared with all other origins of admission, and higher mortality rates compared with the outpatient direct admits and CCF Main Campus ED admits. After adjusting for disease severity and risk of mortality, OSH ED patients remained at higher risk for Adult Medical Emergency Team activation, OSH inpatient transfers had the longest LOS, and CCF Main Campus ED patients had the lowest risk of mortality. Time of admission and provider type were not associated with any of the outcomes. CONCLUSION: Oncology inpatients transferred from an outside health care facility are at higher risk for adverse outcomes. The magnitude of difference is lessened, but still significant, after adjustment for disease severity and risk of mortality.

Comparative Effectiveness of Busulfan and Fludarabine versus Fludarabine and 400 cGy Total Body Irradiation Conditioning Regimens for Acute Myeloid Leukemia/Myelodysplastic Syndrome.

Allogeneic hematopoietic cell transplantation conditioning regimen intensity has varied for patients with acute myeloid leukemia and myelodysplastic syndrome. A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus those of fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 received FluTBI. The BuFlu group received more red blood cell transfusions (P = .02) and had a longer time to platelet recovery (P = .004). There were no differences between the regimens regarding incidence of acute or chronic graft-versus-host disease (GVHD), quality of life, or 2-year outcome estimates for relapse (48; 95% confidence interval [CI], 30 to 64 and 50; 95% CI, 33 to 65), nonrelapse mortality (29; 95% CI, 14 to 45 and 29; 95% CI, 15 to 44), relapse-free survival (27; 95% CI, 13 to 43 and 29; 95% CI, 16 to 44), and overall survival (35; 95% CI, 19 to 51; and 37; 95% CI, 22 to 52), respectively. These comparable outcomes have implications for health care resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and additional strategies to prevent relapse and limit toxicities as well as cost-effectiveness analyses are warranted.

Hope, Symptoms, and Palliative Care.

BACKGROUND: Hope is important to patients with cancer. Identifying factors that influence hope is important. Anxiety, depression, fatigue, and pain are reported to impair hope. The objective of this study was to determine whether age, gender, marital status, duration of cancer, symptoms, or symptom burden measured by the sum of severity scores on the Edmonton Symptom Assessment Scale (ESAS) correlated with hope measured by the Herth Hope Index (HHI). METHODS: Patients with advanced cancer in a palliative care unit participated. Demographics including age, gender, marital status, cancer site, and duration of cancer were collected. Individuals completed the ESAS and HHI. Spearman correlation and linear regression were used to assess associations adjusting for gender (male vs female), age (< 65 vs ≥ 65 years), marital status (married or living with a partner vs other), and duration of cancer (≤ 12 vs > 12 months). RESULTS: One hundred and ninety-seven were participated in the study, of which 55% were female with a mean age of 61 years (standard deviation 11). Hope was not associated with gender, age, marital status, or duration of cancer. In univariable analysis, hope inversely correlated with ESAS score (-0.28), lack of appetite (-0.22), shortness of breath (-0.17), depression (-0.39), anxiety (-0.32), and lack of well-being (-0.33); only depression was clinically relevant. In multivariable analysis, total symptom burden weakly correlated with hope; only depression remained clinically significant. DISCUSSION: This study found correlation between symptom burden and hope was not clinically relevant but was so for depression. CONCLUSION: Among 9 ESAS symptoms, only depression had a clinically relevant correlation with hope.

Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes.

PURPOSE: Preoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted. METHODS: Between 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50 mg/m2 d1, oxaliplatin 130 mg/m2 d1, and fluorouracil 200 mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 cycles and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy @ 1.8-2.0 Gy/day and 2 cycles of cisplatin (20 mg/m2/day) and fluorouracil (1000 mg/m2/day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. RESULTS: Persistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43-8.43), p = 0.006], recurrence free survival [HR 3.04 (1.34-6.92), p = 0.008], and overall survival [HR 3.31 (1.43-7.66), p = 0.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (p = 0.048) and N descriptor (pN) (p = 0.002), a greater median number of involved lymph nodes (3 v 1, p = 0.003), and greater residual tumor viability (p = 0.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease. CONCLUSIONS: Persistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.

Importance of residual primary cancer after induction therapy for esophageal adenocarcinoma.

OBJECTIVES: To (1) assess the continuous distribution of the percentage of residual primary cancer in resection specimens after induction therapy for locally advanced esophageal adenocarcinoma, (2) determine the effects of residual primary cancer on survival after esophagectomy, (3) ascertain interplay between residual primary cancer and classical classifications of response to induction therapy (ypTNM), and (4) identify predictors of residual primary cancer. METHODS: From January 2006 to November 2012, 188 patients (78%) underwent accelerated chemoradiotherapy, and 52 patients (22%) underwent chemotherapy alone followed by esophagectomy for adenocarcinoma. Mean age was 61 ± 9.2 years, and 89% were male. Residual primary cancer, assessed as the percentage of residual primary cancer cells in resection specimens, was quantified histologically by a gastrointestinal pathologist. Random Forest technology was used for data analysis. RESULTS: Twenty-five specimens (10%) had no residual primary cancer (ypT0), 79 (33%) had 1% to 25% residual cancer, 91 (38%) had 26% to 75%, and 45 (19%) had >75%. Survival was worse with increasing residual primary cancer, plateauing at 75%. Greater residual primary cancer was associated with worse survival across the spectrum of higher ypTN. Higher ypT, larger number of positive nodes, and use of induction chemotherapy rather than induction chemoradiotherapy were associated with greater residual primary cancer. CONCLUSIONS: Less residual primary cancer in response to preoperative therapy is associated with a linear increase in survival after esophagectomy for locally advanced esophageal adenocarcinoma; however, survival is poorer than for resected early-stage cancers. Therefore, for patients with poor prognostic indicators, including higher percentage of residual primary cancer, the role of adjuvant therapy needs to be further examined in an attempt to improve survival.

Mesenteric Arteriovenous Dysplasia/Vasculopathy Is Distinct From Fibromuscular Dysplasia.

Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic vasculopathy that usually affects the carotid and renal arteries. We have observed FMD-like vascular changes in specimens resected for ischemia or Crohn's disease (CD). On the basis of a systematic clinicopathologic review of these 11 cases identified between 1982 and 2014, we describe a distinct mesenteric vasculopathy that involves both arteries and veins [mesenteric arteriovenous dysplasia/vasculopathy (MAVD/V)] and is characterized by (1) concentric/eccentric smooth muscle collarette around the tunica media of both the artery and the vein in ≥2 foci, (2) varying degrees of intimal and medial hyperplasia and adventitial fibrosis, and (3) lack of inflammation or thrombi. MAVD/V cases were clinically diagnosed as CD (45%), mass/lesion (27%), ischemia (9%), obstruction (9%), or rectal prolapse (9%). Abdominal pain for >1 year was the most common symptom. Most patients were women (M:F=1:2.7; mean age, 63 y). Mucosal changes mimicking CD, such as architectural distortion (55%), multifocal ulcers (73%), and pyloric gland metaplasia (64%), were common; however, no granulomas or transmural lymphoid aggregates were identified. Ischemic pattern of injury was seen in 4 cases. Upon follow-up (mean, 31.2 mo), 8 patients were found to be asymptomatic, 2 had died of unrelated causes, and 1 was lost to follow-up. We propose the name MAVD/V for a distinct noninflammatory, nonatherosclerotic, localized form of mesenteric vasculopathy that involves both arteries and veins, distinct from FMD. Unlike FMD, surgical resection appears to be curative, with a favorable clinical outcome. Awareness of this vascular entity is important as patients may be potentially misdiagnosed as having CD and ischemic bowel disease.