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A 41-year-old man presented to his primary care physician with a 1-month history of left neck adenopathy in the context of a history of nonseminomatous germ cell tumors (NSGCTs). In 2011, the patient was treated for stage IB (T2N0M0S0) right-sided NSGCTs of the testis, which were 95% embryonal and 5% yolk sac tumors. He underwent a right radical orchiectomy and was followed until 2022 without recurrence. In the work-up for his adenopathy, laboratory results for human chorionic gonadotropin, lactate dehydrogenase, and [alpha]-fetoprotein were normal. CT scans confirmed clustered enlarged lymph nodes in the left lower spinal accessory posterior triangle, enlarged left lower neck lymph nodes, and several foci of enlarged left retroperitoneal periaortic lymph nodes. Fine needle aspiration of a left neck lymph node identified malignant tumor cells. A left neck dissection showed embryonal carcinoma in 12 of 28 nodes. Immunostaining showed the tumor cells were positive for SALL4 and CD30 but negative for CD117. This patient likely had a contralateral late relapse of his original right NSGCT after 11 years of remission. The patient's original cancer was on the right side, with recurrence surrounding the aorta on the contralateral side, representing an atypical pattern of spread., Case Report A 41-year-old Asian man presented to his primary care physician (PCP) in January 2023 with a 1-month history of left neck adenopathy in the context of a prior [...]

The homologous recombination repair (HRR) pathway is a frequently mutated pathway in advanced prostate cancer. The clinical course of patients with HRR gene alterations who have metastatic hormone sensitive prostate cancer (mHSPC) has not been fully characterized. Here, we examine the outcomes of men with mHSPC with HRR alterations.

Background: Little is known about the true rate of pathogenic (P)/likely pathogenic (LP) germline alterations in Hispanic men with prostate cancer as most studies analyzing the prevalence of P/LP germline alterations were performed in a largely non-Hispanic white population (NHW). Methods: We performed a retrospective analysis of two separate cohorts of men with prostate cancer: (1) a multicenter cohort of 17,256 men who underwent germline testing in a CLIA-certified laboratory and (2) a single-center cohort of all men eligible for germline testing between 2018 and 2020. The proportions of P/LP alterations and variants of uncertain significance (VUS) were computed. Fisher’s exact test was used to compare germline alteration rates for significance. A multivariate logistic regression was performed adjusting for demographic and clinical factors to examine factors associated with germline testing. Results: In the multicenter cohort, the rate of P/LP germline alterations among self-reported Hispanic men was 7.1%, which was lower than self-reported NHW men (9.7% vs. 7.1%, p= 0.058), but was not statistically significant. The VUS rate was significantly higher among the Hispanic cohort (21.5% vs. 16.6%, p= 0.005). In the single-center cohort, 136 Hispanic patients were eligible for testing of which 34 underwent germline testing (26.1%, N= 34/136). Of all prostate cancer patients in the single-center cohort undergoing germline testing (n= 173), the rate of P/LP alterations in Hispanic patients was not significantly different compared to NHW patients (14.7% vs. 12.2%, p= 0.77). The rate of VUS in Hispanic patients was significantly higher than that of NHW patients (20.6% vs. 7.2%, p= 0.047). Conclusion: The P/LP germline alteration rate in our cohorts was similar between Hispanic and NHW men. The rate of VUS was significantly higher in Hispanic men, a consequence of undertesting in minority populations. These data support that Hispanic men with prostate cancer should be screened for germline testing similar to NHW men.

There has been considerable interest in ctDNA next generation sequencing platforms to assess genomic alterations in mCRPC given its accessibility and identification of temporal genomic data.

We analyzed outcomes of neoadjuvant sunitinib in patients with renal-cell carcinoma (RCC) and inferior vena caval (IVC) tumor and compared outcomes to patients who did not undergo neoadjuvant therapy before surgery.

Neoadjuvant sunitinib might facilitate partial nephrectomy (PN) in imperative indications. We performed a retrospective comparison of functional outcomes in patients who had and had not received neoadjuvant sunitinib before PN for imperative indications. We noted similar renal functional outcomes between the 2 groups. To the best of our knowledge, these findings represent the first such reported comparison.

Telomerase reverse transcriptase (TRT) is the first bona fide common tumor antigen. While several 9mer peptides of the human TRT have been identified for HLA-A2, little information exists on peptides for the remaining HLA types. Here, we used a multi-step approach to select and characterize a panel of HLA-B7 9mer peptides as candidate immunogens. In sequence, we used algorithm-based predictions, in vivo immunization of HLA-B7 transgenic (Tg) mice, in vitro immunization of human blood lymphocytes from two normal donors and two cancer patients, in vivo processing in HLA-B7 Tg mice and HLA-B7 supertype binding. We found a correlation between the in vivo immunogenicity and the actual HLA-B7 binding avidity of the seven predicted peptides. Furthermore, endogenous processing correlated with in vitro immunogenicity in human PBMC and HLA-B7 supertype binding. Peptide 1123LPSDFKTIL1131 (p1123) with the wider spectrum of supertype binding displayed the highest immunogenicity overall and was endogenously processed in several human lymphoblastoid cells. Since no single step of the screening/selection process could substitute for the whole approach, we conclude that the identification of MHC class I-restricted peptides for potential vaccination of cancer patients remains, by and large, an empirical process.

Purpose:The CALGB conducted a phase II multicenter trial to evaluate the activity of gemcitabine in malignant mesothelioma (CALGB protocol 9530). Patients and methods:Seventeen patients were accrued between February 1996 and May 1996 and received gemcitabine 1500 mg/m2by intravenous infusion over 30 min weekly for 3 weeks, followed by a 1 week break. Eligibility included a performance status of 0–2 by CALGB criteria, and no prior chemotherapy. Nine patients had epithelial cell type and eight had mixed or sarcomatoid cell types. There were 11 cases with measurable disease and six with evaluable disease. Results:There were no complete or partial responders. Eight patients had stable disease, seven developed progressive disease, and two were not evaluable for tumor response. Two patients had minor responses. Median survival from study entry was 4.7 months (95% CI 3.1–12.9 months); one year survival was 24% (95% CI 10–55%). One patient remains alive at 37 months. There were two early deaths, one from disease progression and one from pneumonia. Toxicity was mild and included anemia, lymphopenia and infection; no patient experienced grades three or four thrombocytopenia. Conclusion:No antitumor activity was observed for single-agent gemcitabine in patients with malignant mesothelioma in this multicenter phase II study.

The markers, CD11 b, CD11 c, CD14, CD21, CD23, CD25, CD38, and FMC7 were correlated with morphologic and other laboratory and clinical characteristics of 127 patients with untreated CD5+chronic lymphocytic leukemia (CLL). Only CD38 and CD21 were significantly associated with atypical CLL morphology. The integrin associated markers CD11 b and CD11c were associated with lower leukocyte count (white blood cell count [WBC]) and lower Rai stage. By contrast, the activation antigen CD23 was associated with a higher WBC, higher Rai stage, younger age group, and the presence of lymphadenopathy. Therefore, we conclude that CD23 positivity may reflect a more aggressive form of CLL, and CD11b and CD11c positivity a less aggressive form. The BCL-1 gene rearrangement was present in 5 of 84 (6%) CLL cases examined and was associated with atypical morphology and surface expression of CD11b. Patients with a BCL-1 gene rearrangement may represent a CLL subset or possibly a different B-cell disease.

Sepsis is a common cause of morbidity and mortality. Neutrophils are the major defense against bacterial invasion, and granulocyte colony-stimulating factor (G-CSF) augments both neutrophil number and function. In our study, 160 rabbits were inoculated transtracheally with 0.5 mL of a solution containing 104colony forming units per milliliter of Pasteurella multocida.Twenty-four hours later, chest x-rays and quantitative blood cultures demonstrated pneumonia and bacteremia. Therapy was then begun with penicillin G and either recombinant human G-CSF (rG-CSF; 5 to 8 μg/ kg subcutaneously) or placebo every day for 5 days. Arterial blood gases and 23 other parameters of organ function were performed before inoculation and serially thereafter. All rabbits underwent histologic examination of organs at the time of septic death or when sacrificed on day 6. A total of 149 rabbits survived long enough to initiate therapy. A significant increase in leukocytes by day 4 was found in the rG-CSF–treated group. There was a trend towards improved survival in the rG-CSF group (77% v67%; P= .13, n = 149). Analysis of pretreatment variables revealed sepsis-induced leukopenia (≤2,800/μL) as the only predictor of significantly improved survival with rG-CSF treatment (57% v39%; P= .04, n = 73). The majority of the survival benefit occurred within the first 24 hours of treatment. This was before the time that a significant difference in mean white blood cell (WBC) count was observed between the study groups, making intravascular leukocytosis an unlikely explanation for the survival advantage in the rG-CSF group. No significant difference in laboratory variables reflecting organ function was demonstrated between the groups. Histologic grading of inflammation (0, normal, to 6, necrosis) in seven organs revealed that the surviving rabbits had mild but statistically significant increased inflammation in the liver, spleen, and noninoculated lung in the rG-CSF versus placebo groups (liver: 2.6 v1.5, P≤ .0001; spleen: 3.2 v2.3, P≤ .0001; and noninoculated lung: 2.9 v2.5, P= .04). Administration of rG-CSF, in addition to penicillin G, in immune competent rabbits with gram-negative sepsis complicated by leukopenia significantly improved survival over antibiotics alone. The administration of rG-CSF in early sepsis for a short therapeutic duration was not associated with any clinically evident toxicity. Clinical trials using rG-CSF in septic patients with leukopenia are indicated.

Alloimmunization to donor class I HLA antigens represents a major obstacle to successful platelet transfusion therapy. It is desirable to distinguish alloimmunization from nonimmunologic causes of poor platelet survival to assess the need for HLA-matched, single-donor platelets. We describe a new in vitro assay for anti-HLA antibodies and report its application to the problem of platelet crossmatching. In contrast to previously described crossmatch techniques, the immunobead assay is specific for anti-HLA antibodies. The assay was used to evaluate 51 single-donor platelet transfusions given to seven patients from 35 different donors. Recipient plasma was assayed for antibodies directed against HLA antigens present on donor platelets. A one-hour posttransfusion corrected count increment of ≥7,500 was considered a successful outcome. Twenty-nine of 33 (87.9%) transfusion episodes associated with a negative immunobead assay had successful outcomes. The four unsuccessful transfusions were associated with potential nonimmunologic causes of poor platelet survival. Only two of 18 (11.1%) episodes associated with a positive assay had successful outcomes. Only one unsuccessful transfusion episode was associated with a negative immunobead assay and a positive radiolabeled antiglobulin test result, which suggested that isolated alloantibodies to antigens other than class I HLA antigens are not a common cause of platelet refractoriness. Platelets stored in suspension at 4°C or frozen in liquid nitrogen were found suitable for crossmatch testing. © 1987 by Grune & Stratton, Inc.