Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy.

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.

Characteristics of appendicitis after immune checkpoint inhibitor therapy among cancer patients.

PURPOSE: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer care but is associated with immune-related adverse events (irAEs). Recent case reports raised the concern that acute appendicitis may be an irAE. In this study, we sought to describe the disease course of post-ICI therapy appendicitis and its associated complications. METHODS: Adult patients who had an International Classification of Diseases code for appendicitis within the first 2 years after initiating ICI therapy from January 2010 to April 2021 and who had imaging evidence of appendicitis were studied retrospectively. RESULTS: 13,991 patients were identified who had ICI exposure during the study period, 44 had codes for appendicitis, 10 of whom met the inclusion criteria. Their median age at the time of diagnosis was 59 years. The median time from ICI therapy initiation to appendicitis onset was 188 days. The most common presenting symptoms were abdominal pain (70%) and fever (40%). Abscesses were present in two patients, and a perforation was present in one. All 10 patients received broad-spectrum antibiotics. Five patients needed surgery or interventional radiology drainage. Nine patients had resolution of appendicitis symptoms after treatment. CONCLUSION: Post-ICI therapy appendicitis is rare but presents similarly to and has similar complications rates as conventional appendicitis. Appendectomy remains the mainstay of treatment, but its use can be limited in cancer patients. The decision to continue ICI therapy remains at the discretion of the clinician. Further studies are needed to bring awareness to and advance the understanding of this clinical entity.

Role of progenitor cell marker CD133 in supporting diagnosis of collapsing glomerulopathy.

PURPOSE: A previous immunofluorescent study suggests that, in collapsing glomerulopathy, most hyperplastic podocytes that stained positively for a progenitor cell marker CD133 are derived from CD133 + parietal epithelial cells. In pathology practice, not all renal biopsies with collapsing glomerulopathy show the typical morphologic features for this entity, which include florid podocyte hyperplasia, collapsing glomerular capillary loops, and cystic tubular dilation. This study was made to determine if CD133 staining using an immunohistochemical method can be used to confirm hyperplastic podocytes and identify extensive acute tubular injury in collapsing glomerulopathy. METHODS: Twenty-one collapsing glomerulopathy biopsies were stained for CD133 and compared with 15 biopsies with focal segmental glomerulosclerosis, not otherwise specified (FSGS). RESULTS: All patients with collapsing glomerulopathy were of African American descent with prominent renal failure and nephrotic range proteinuria. In contrast, the FSGS group consisted of patients from a variety of ethnic backgrounds with nephrotic range proteinuria but relatively low serum creatinine. The striking finding was that all collapsing glomerulopathy cases showed positive CD133 staining in the clusters of hyperplastic podocytes. There was significantly higher CD133-positive staining rate for hyperplastic podocytes (38%) in the glomeruli of the collapsing glomerulopathy group when compared to small clusters of hyperplastic podocytes in the FSGS group (8%). In addition, when compared to the relatively weak CD133 staining in the proximal tubules of the FSGS group, the proximal tubules of the collapsing glomerulopathy group all showed diffuse and strong CD133 staining as a feature of severe acute tubular injury, which corresponded to the high serum creatinine levels in these patients. CONCLUSION: Our data indicate that the combination of the distinctive mosaic CD133 staining in hyperplastic podocytes and the diffuse tubular CD133 staining is helpful in supporting a diagnosis of collapsing glomerulopathy.

A Novel Method Enables General Pathologists to Create Web Dynamic Forms for Synoptic Tumor Reporting.

CONTEXT.­: Tumor reporting constitutes a significant daily task of pathologists. An efficient tumor-reporting methodology is thus vitally important. The Web dynamic form (WbDF) method offers a multitude of advantages over the prevailing transcription-mediated reporting method based on static-text checklists. However, its adaptation has been severely hampered for 2 decades by its costly needs to maintain a complex back-end system and to change the system for frequent updates of reporting content. OBJECTIVE.­: To overcome these 2 obstacles with a serverless Web platform that enables users to create, customize, use, and download WbDFs as synoptic templates for structured tumor reporting. DESIGN.­: Deploy ReactJS as a Web platform. Create form components in JavaScript Object Notation files. Use JavaScript Object Notation files to make WbDFs on the Web platform. Use the WbDFs to generate final pathology reports. RESULTS.­: Ordinary users (pathologists) can create/customize reporting templates as WbDFs on the Web platform. The WbDF can be used to make a pathology report and stored/shared like ordinary document files. There is no back-end system to change, nor a requirement for computer programming skills. CONCLUSIONS.­: This strategy eliminates the need for a complex back-end system and the associated cost when updating tumor-reporting standards, making it possible to adopt the WbDF method without the technological drawbacks associated with content updates. It also opens a new field of how the tumor-reporting system should be organized, updated, and implemented.

Kidney injury molecule-1, a sensitive and specific marker for identifying acute proximal tubular injury, can be used to predict renal functional recovery in native renal biopsies.

Kidney injury molecule-1 (KIM-1) staining has been shown to be very useful in identifying acute proximal tubular injury, but its sensitivity, specificity and predicting values for the recovery of renal function after injury in renal biopsies have not been well established. In the first study, we randomly selected 184 renal biopsies from a wide age range of patients (children to elderly) with various renal diseases. KIM-1 staining scores were significantly correlated with serum creatinine (sCr) levels (P < 0.05) in all age groups. Receiver-operating characteristic curve (ROC) was generated to evaluate true-positive rate (sensitivity) and true-negative rate (1-specificity). The area under the curve (AUC) in pediatric cases was 0.74, which demonstrated KIM-1 was a fair index in correlating with sCr. In adults, the AUC was 0.87, indicating that KIM-1 was an even better index in the adult population in correlating to sCr. The second study was to determine whether KIM-1 could be a potential predictor of the recovery of acute kidney injury (AKI), and 51 indicated native biopsies with acute tubular injury were randomly selected for KIM-1 staining and sCr follow-up over a 6-month period. A higher KIM-1/sCr ratio (0.57 ± 0.06) was significantly and positively associated with a better reduction in sCr over 6 months. In summary, our data demonstrated that KIM-1 staining in renal biopsies is a sensitive and specific marker to identify acute tubular injury and KIM-1/sCr ratio is useful for predicting the recovery of renal function after injury, although some patients' sCr levels cannot return to their baseline levels.

Monoclonal Gammopathy of Renal Significance and its Associated Experimental Models.

Monoclonal gammopathy of renal significance (MGRS) is a state of circulating monoclonal immunoglobulin (Ig) and light chains that cause kidney injury without definite evidence of multiple myeloma (MM). Although chemotherapy is used to treat many variants of MGRS and has been recently recommended, relatively limited clinical validation studies are available. A few transgenic models of MM reveal renal deposition of monoclonal Ig and light chains. We have demonstrated that the XBP1s-transgenic mouse model from early plasma cell dyscrasia to MM reveals monoclonal IgG/kappa deposition at the subendothelial spaces of the glomeruli, mimicking proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Inhibition of a key immune-modulator, gp96/grp94, genetically or pharmacologically results in a significant reduction of plasma cells within the bone marrow and reduced renal deposition of monoclonal IgG and kappa light chain. This article will review the emerging role of in vitro and animal models from plasma cell dyscrasia to MM in understanding the renal deposition of monoclonal Ig and light chains, along with its potential treatment strategies.

Physical Health Conditions Among a Population-Based Cohort of Vietnam-Era Women Veterans: Agreement Between Self-Report and Medical Records.

BACKGROUND: Little is known about medical morbidity among women Vietnam-era veterans, or the long-term physical health problems associated with their service. This study assessed agreement comparing data on physical health conditions from self-report and medical records from a population-based cohort of women Vietnam-era Veterans from the Health of Vietnam Era Women's Study (HealthViEWS). MATERIALS AND METHODS: Women Vietnam-era veterans (n = 4219) self-completed a survey and interview on common medical conditions. A subsample (n = 900) were contacted to provide permission to obtain medical records from as many as three of their providers. Medical record reviews were conducted using a standardized checklist. Agreement and kappa (agreement beyond chance) were calculated for physical health condition groups. RESULTS: Of the 900, 449 had medical records returned, and of those, 412 had complete surveys/interviews. The most commonly reported conditions based on self-report or medical record review included hypertension, hyperlipidemia, or arthritis. Kappa scores between self-reported conditions and medical record documentation were 0.75-0.91 for hypertension, diabetes, most cancers, and neurological conditions, but lower (k = 0.29-0.55) for cardiovascular diseases, musculoskeletal, and gastrointestinal conditions. Generally, agreement did not significantly vary by different sociodemographic groups. CONCLUSIONS: There was relatively high agreement for physical health conditions when self-report was compared with medical record review. As more women are increasingly represented in the military and more veterans in general seek care outside the Veterans Health Administration, accurate measurement of physical health conditions among population-based samples is crucial.

Cause-specific mortality among Veterans with serious mental illness lost to follow-up.

OBJECTIVE: Although reduced care engagement has been linked to increased mortality for persons with serious mental illness (SMI), there have been limited investigations into specific mortality causes for this group. This study evaluates the effects of care disengagement on mortality cause and time until death in Veterans with SMI. METHOD: A total of 3300 Veterans with SMI lost to Veterans Affairs care for more than 1 year were contacted by providers who attempted treatment reengagement. Fisher's Exact Tests evaluated associations between mortality cause and reengagement status, and a Cox proportional hazard model evaluated the association between reengagement and survival. RESULTS: During the study, 146 (4.6%) patients died. A lack of reengagement was associated with increased noninjury death [odds ratio (OR)=1.64], increased cancer-based mortality (OR=4.76) and an average of 97.4 fewer days of life. CONCLUSIONS: Care reengagement may support medical care management and reduce preventable medical mortality for Veterans with SMI.

Design and rationale of a randomized controlled trial to reduce cardiovascular disease risk for patients with bipolar disorder.

BACKGROUND: Persons with bipolar disorder (BD) experience a disproportionate burden of medical comorbidity, notably cardiovascular disease (CVD), contributing to decreased function and premature mortality. We describe the design, rationale, and baseline findings for the Self-Management Addressing Heart Risk Trial (SMAHRT), a randomized controlled effectiveness trial of an intervention (Life Goals Collaborative Care; LGCC) designed to reduce CVD risk factors and improve physical and mental health outcomes in patients with BD. METHODS: Patients with BD and at least one CVD risk factor were recruited from a VA healthcare system and randomized to either LGCC or usual care (UC). LGCC participants attended four weekly, group-based self-management sessions followed by monthly individual contacts supportive of health behavior change and ongoing medical care management. In contrast, UC participants received monthly wellness newsletters. Physiological and questionnaire assessments measured changes in CVD outcomes and quality of life (QOL) over 24 months. RESULTS: Out of the 180 eligible patients, 134 patients were enrolled (74%) and 118 started the study protocols. At baseline (mean age=54, 17% female, 5% African American) participants had a high burden of clinical risk with nearly 70% reporting at least three CVD risk factors including, smoking (41%) and physical inactivity (57%). Mean mental and physical HRQOL scores were 1.5 SD below SF-12 population averages. CONCLUSION: SMAHRT participants experienced substantial CVD morbidity and risk factors, poor symptom control, and decreased QOL. LGCC is the first integrated intervention for BD designed to mitigate suboptimal health outcomes by combining behavioral medicine and care management strategies.

Mood disorder symptoms and elevated cardiovascular disease risk in patients with bipolar disorder.

OBJECTIVES: We examined the association between mood symptoms and 10-year CVD risk estimated by Framingham risk score in a cohort of patients with bipolar disorder. METHODS: Veterans with bipolar disorder and CVD risk factors (N=118) were recruited from outpatient VA clinics. CVD risk factor data were collected from electronic medical records and patient surveys, and used to calculate patient Framingham Scores. The relationship between mood symptoms (depressive, manic) and Framingham scores was examined, as was the relationship between mental health symptoms and individual CVD risk factors (lipids, blood pressure, weight, smoking, and fasting glucose). RESULTS: Mean sample age was 53 years (SD=9.9), 17% were female, and 5% were African-American. Almost 70% were obese (BMI≥30), 84% had hyperlipidemia, 70% were hypertensive, and 25% had diabetes. Nineteen percent had a Framingham score of >20%, indicative of elevated 10-year risk of developing CVD. After adjusting for age, gender, diabetes diagnosis, smoking status, and mood symptoms, patients with clinically significant depressive symptoms had a 6-fold increased odds of having a Framingham score of >20% (OR=6.1, p=0.03) while clinically significant manic symptoms were not associated with the Framingham score (OR=0.6, p=0.36). Depressive symptoms were also associated with elevated BMI, fasting glucose, and blood pressure. LIMITATIONS: Single-site study reliant on cross-sectional and self-reported mood measures. CONCLUSION: After controlling for physiologic correlates, depressive symptoms were associated with greater relative 10-year risk for CVD mortality among patients with bipolar disorder. Interventions that address self-management of depressive symptoms may help persons with bipolar disorder decrease CVD risk.

Quality of general medical care among patients with serious mental illness: does colocation of services matter?

OBJECTIVE: This study was conducted to determine whether patients with serious mental illness receiving care in Veterans Affairs (VA) mental health programs with colocated general medical clinics were more likely to receive adequate medical care than patients in programs without colocated clinics based on a nationally representative sample. METHODS: The study included all VA patients with diagnoses of serious mental illness in fiscal year (FY) 2006-2007 who were also part of the VA's External Peer Review Program (EPRP) FY 2007 random sample and who received care from VA facilities (N=107 facilities) with organizational data from the VA Mental Health Program Survey (N=7,514). EPRP included patient-level chart review quality indicators for common processes of care (foot and retinal examinations for diabetes complications; screens for colorectal health, breast cancer, and alcohol misuse; and tobacco counseling) and outcomes (hypertension, diabetes blood sugar, and lipid control). RESULTS: Ten out of 107 (10%) mental health programs had colocated medical clinics. After adjustment for organizational and patient-level factors, analyses showed that patients from colocated clinics compared with those without colocation were more likely to receive foot exams (OR=1.87, p<.05), colorectal cancer screenings (OR=1.54, p<.01), and alcohol misuse screenings (OR=2.92, p<.01). They were also more likely to have good blood pressure control (<140/90 mmHg; OR=1.32, p<.05) but less likely to have glycosylated hemoglobin <9% (OR=.69, p<.05). CONCLUSIONS: Colocation of medical care was associated with better quality of care for four of nine indicators. Additional strategies, particularly those focused on improving diabetes control and other chronic medical outcomes, might be warranted for patients with serious mental illness.

Isolation of Aspergillus in critically ill patients: a potential marker of poor outcome.

OBJECTIVE: Recent reports have suggested a rising incidence of pulmonary aspergillosis in intensive care unit (ICU) patients. The aim of this study was to determine the clinical significance of isolating Aspergillus from respiratory samples of critically ill patients. DESIGN: Retrospective review of medical records. SETTING: Tertiary medical center that has a large cancer center. PATIENTS: All patients admitted to the ICU between January 1998 and August 2004, in whom Aspergillus was isolated from respiratory samples or lung tissue. INTERVENTION: None. RESULTS: The charts of 104 patients were reviewed. Aspergillus was isolated for a mean of 6.6 days after ICU admission. Thirty-three percent of patients had hematological malignancy, 10% had absolute neutropenia, 14% had bone marrow transplant, 11% had HIV infection, and 22% had chronic obstructive pulmonary disease. Upon admission to ICU, 79%, 43%, and 19% were on antibiotics, corticosteroids, or immunosuppressive therapy, respectively. Ninety percent of patients required mechanical ventilation. The mean Acute Physiologic and Chronic Health Evaluation II score on ICU admission was 20.6, with predicted mortality of 35.5%. However, the actual ICU mortality rate for the cohort was 50%. Twenty-eight percent of patients were diagnosed with probable or definite invasive pulmonary aspergillosis, and 72% had Aspergillus colonization. On univariate analysis, the significant clinical differences between the 2 groups were the presence of neutropenia (P < .05), immunosuppressants (P < .05), antibiotics (P < .05), or bone marrow transplant (P < .05). The differences in Acute Physiologic and Chronic Health Evaluation II score, the need for mechanical ventilation, ICU length of stay, and ICU mortality were not statistically significant. On multivariate analysis, the following factors were independently associated with invasive diseases, bone marrow transplantation (P < .01), hematological malignancy (P = .02), and broad-spectrum antibiotics (P = .02). CONCLUSION: Isolation of Aspergillus in critically ill patients is a poor prognostic marker and is associated with high mortality irrespective of invasion or colonization. Those who are neutropenic, on immunosuppressive therapy, on broad-spectrum antibiotics, or had bone marrow transplantation are more likely to have invasive pulmonary aspergillosis.

Intermittent hormone therapy in nonmetastatic prostate cancer.

PURPOSE: The object of this study was to evaluate the duration of response to intermittent androgen deprivation (IAD) in patients with nonmetastatic recurrent or localized prostate cancer. PATIENTS AND METHODS: One hundred ten patients received IAD from February 1992 to February 2005. One hundred three patients were treated after failure of primary radiation therapy and/or prostatectomy, with the remaining 7 patients treated primarily with IAD. The median duration of treatment cycle was 6 months. Patients were considered resistant to hormone therapy if the prostate-specific antigen (PSA) level increased, with castrate levels of testosterone. At the time of initial diagnosis, the median Gleason score was 7 (range, 4-9), and tumor stages were as follows: T1/T2 (n = 73), T3 and T4 N1 (n = 34), and other (n = 3). The median PSA at the initiation of IAD was 8.25 ng/mL. RESULTS: The median follow-up after beginning IAD was 45.5 months. Patients received a median of 2 cycles (range, 1-9 cycles). Ninety-four of 110 patients (85.5%) remained responsive to IAD. Sixteen patients (14.5%) progressed to become refractory to primary hormone treatment. Patients with a higher tumor stage (T3 and T4) were significantly more likely to develop resistance. The median time to become refractory to hormone therapy was 47.9 months (range, 9.4-93.4 months). Five patients were put on secondary continuous hormone treatment, and 3 of them developed resistance at a median of 9 months. One patient was put on a secondary IAD and was still responding at the last follow-up. CONCLUSION: With 85.5% of the original patient population still responding to the primary hormone therapy at 45.5 months of follow-up, IAD appears to be a viable option for patients with biochemical failure after local radiation therapy. A pattern of shortening time between cycles and an increasing nadir PSA level with each successive cycle is consistent with the gradual development of hormone resistance.

Detection of carotid stenosis in African Americans with ischemic heart disease.

OBJECTIVES: This study was conducted to define the frequency of internal carotid stenosis in African American patients with ischemic heart disease (IHD). METHODS: We recruited 101 African American patients with IHD from a university medical center for carotid duplex examination. RESULTS: The frequency of >30%, >50%, and >70% stenosis was 21%, 11%, and 5%, respectively. Age >60 years (21% vs 3%, P < .01) and diabetes mellitus (22% vs 5%, P < .01) were predictors of unilateral stenosis of >50% and remained significant on multivariate testing. CONCLUSION: African American patients with established IHD have higher rates of extracranial carotid stenosis than community dwelling African American subjects and comparable rates with other populations.

Racial disparity in clinical course and outcome of metastatic androgen-independent prostate cancer.

OBJECTIVES: To perform a review of patient and disease characteristics and response and survival outcomes of patients with metastatic androgen-independent prostate cancer. Racial differences in prostate cancer have usually been attributed to socioeconomic status, quality of care, comorbidities, and dietary factors. In a clinical trial population, some of these factors, such as access to care and performance status, are likely to be relatively uniform. METHODS: The patients included in the review had been registered in clinical trials between 1991 and 2001 at Wayne State University. RESULTS: Of 145 patients, 90 (62%) were white Americans and 55 (38%) were black Americans, 27% were 70 years or older, and 34% had minimal metastatic disease (axial bony involvement and/or lymph node involvement) and 66% had extensive disease (appendicular skeleton and/or visceral involvement). The chi-square test demonstrated no statistically significant difference by race in the distribution of the patient and disease characteristics. The prostate-specific antigen response rate was 41% in whites and 29% in blacks (P = 0.12). Log-rank analysis revealed race to be the only statistically significant factor predictive of the time to prostate-specific antigen progression (P = 0.02, median 4.6 months in whites and 2.3 months in blacks). No statistically significant difference by race was found in overall survival. Poor performance status, extensive disease, elevated alkaline phosphatase and lactate dehydrogenase levels, and a lack of prostate-specific antigen response were statistically significant predictors of worse overall survival. CONCLUSIONS: In patients with androgen-independent metastatic prostate cancer studied in clinical trials, race was an independent predictor of therapeutic outcome. Additional investigation of the biologic and genetic differences underlying this clinical disparity is warranted.

The effect of race/ethnicity on prostate cancer treatment outcome is conditional: a review of Wayne State University data.

PURPOSE: The mortality rate for prostate cancer in black American men (AAMs) is 2 times greater than that in other ethnic groups. However, there is considerable controversy as to whether race/ethnicity is an independent predictor of survival outcome. We present conditions in which race/ethnicity is and is not an independent predictor of survival outcomes. MATERIALS AND METHODS: We examined the conditions of age, stage and year of diagnosis, and the role of race/ethnicity on disease-free survival in men who underwent consecutive radical prostatectomy as monotherapy from 1990 to 1999. Data were collected from 229 AAMs and 562 white American men prospectively in the Karmanos Cancer Institute Prostate cancer data bases. RESULTS: When the majority of the cohort had pathologically organ confined disease, race/ethnicity was not an independent predictor of disease-free survival. When the majority of the cohort had a mean age of 70 years or greater, race/ethnicity was not an independent predictor. In studies done in the late 1990s, when the stage of radical prostatectomy cases had shifted toward pathologically organ confined disease as the dominant stage, race/ethnicity was not an independent predictor. However, if the cohort was diagnosed at younger age and/or with more advanced prostate cancer, race/ethnicity became an independent predictor. In the early 1990s there was pathologically advanced disease in the majority of our cohort. CONCLUSIONS: Race/ethnicity as an independent predictor of prostate cancer is conditional and dependent on age, stage and year of diagnosis. Year of diagnosis is associated with a stage shift to earlier staged prostate cancer from the early to late 1990s. In general, study cohorts are often subranges of the entire spectrum of prostate cancer that are limited by these factors, especially stage at diagnosis and treatment. If diagnosed and treated early enough, although there is evidence suggesting that AAMs have more aggressive disease biologically, the role of race as a factor in outcome is significantly decreased. The age factor is more complex and must be discussed in more detail.