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Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers., Methods: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1 + CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed., Results: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1 + CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1 + CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1 + individuals had comparable survival to PD-L1 - individuals, except ICI treatment for which PD-L1 + may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1 + CTCs had worse survival prognosis compared to those without PD-L1 + CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups., Conclusions: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1 + CTCs for ICI treatment needs validation by more large-scale studies in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected "target" lesions over time. At our cancer center, a majority of oncologists use Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 quantifying tumor progression based on lesion measurements on imaging. Currently, our oncologists handwrite tumor measurements, followed by multiple manual data transfers; however, our Picture Archiving Communication System (PACS) (Carestream Health, Rochester, NY) has the ability to export tumor measurements, making it possible to manage tumor metadata digitally. We developed an interface, "Exportable Notation and Bookmark List Engine" (ENABLE), which produces prepopulated RECIST v1.1 worksheets and compiles cohort data and data models from PACS measurement data, thus eliminating handwriting and manual data transcription. We compared RECIST v1.1 data from eight patients (16 computed tomography exams) enrolled in an IRB-approved therapeutic trial with ENABLE outputs: 10 data fields with a total of 194 data points. All data in ENABLE's output matched with the existing data. Seven staff were taught how to use the interface with a 5-min explanatory instructional video. All were able to use ENABLE successfully without additional guidance. We additionally assessed 42 metastatic genitourinary cancer patients with available RECIST data within PACS to produce a best response waterfall plot. ENABLE manages tumor measurements and associated metadata exported from PACS, producing forms and data models compatible with cancer databases, obviating handwriting and the manual re-entry of data. Automation should reduce transcription errors and improve efficiency and the auditing process.

A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. As the major catechins present in green tea are potent antioxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent antioxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared with an age-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared with animals consuming deionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2'deoxyguanosine and 4-hydroxynonenal content (markers of DNA adduct formation and lipid peroxidation, respectively) in the epithelium of the ventral prostate in aging animals. In addition, there was an increase in 8-hydroxy-2'deoxyguanosine expression, but no change in 4-hydroxynonenal expression in the seminal vesicles of older animals. An age-associated increase in expression of the antioxidant enzymes manganese superoxide dismutase and catalase in the epithelium of the ventral prostate of aging animals was observed. Furthermore, there was also an increase in manganese superoxide dismutase expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age-associated DNA adduct formation and lipid peroxidation in the ventral prostate and seminal vesicles of the aging rat.

Context: The percentage of cancer patients > or =80 years old is expected to increase in the next few years. However data on the use of chemotherapy in these patients are limited., Objective: We conducted a retrospective review to define the profile of patients > or =80 years old who received chemotherapy at our center and assess their survival., Design, Setting and Participants: Patients > or =80 years treated with chemotherapy between 1 January 2000 and 31 December 2004 were included in this analysis., Results: Of the 4689 patients treated with chemotherapy over the 5-year period, 133 patients (3%) were > or =80 years old. The median age was 83 years. 61% were females and 39% were males. 16% had hematologic tumors and 84% had solid tumors. Gynecological (32%) and aerodigestive cancers (27%) were the most common sites and lung cancer (22%) was the most common cancer. During the first regimen, 512 cycles of chemotherapy were delivered with a median of 3 cycles (range: 1-24 cycles). 49% received single and 51% multidrug regimens. Carboplatin was the most common single agent and carboplatin and paclitaxel was the most common combination among solid tumor patients. 19% of solid tumor patients received radiation with chemotherapy. The 1-year survival among hematologic cancer and solid tumor patients was 65% and 48%, respectively. Stage of disease was the only statistically significant factor predicting survival., Conclusions: In cancer patients > or =80 years old selected for chemotherapy, both single and multi-agent therapy appeared to be feasible.

The interaction of patients with their doctors impacts the experience of disease at many levels. It is thus important to measure patient satisfaction with such interaction as an outcome of care. Our goal was to investigate whether tumor status influences patient satisfaction with interaction with their doctors. Specifically, we investigated whether patients with no evidence of disease (NED), localized, or metastatic cancers seen in routine follow-up differ in their satisfaction with the oncologist. Outpatients attending clinics at a major cancer center completed a battery of questionnaires, including the Patient Satisfaction with Doctor (PSQ-MD) questionnaire, a 24-item, self-report instrument. It taps two facets of the doctor-patient exchange: perceived support and physician disengagement. Data concerning tumor status and satisfaction were obtained for 569 patients, sampled to include equivalent numbers of women and men with breast, head and neck, gastrointestinal, genitourinary, or lung cancer, or lymphoma. Controlling for age, marital status, annual family income, stressful life events, and employment status, patients with metastatic disease felt somewhat less supported by their physicians (mean=3.26+/-0.06) than those with localized disease (mean=3.42+/-0.04) or NED (mean=3.42+/-0.03), (analysis of covariance, p< 0.05). Physician disengagement did not differ across the groups (means=1.54+/-0.06, 1.43+/-0.04, and 1.47+/-0.03 respectively). These findings were consistent across cancer diagnoses. Patients with metastatic disease may feel less physician support than those with less advanced cancers. Increasing attention to satisfaction of different patient groups can pave the way to improved quality of care.

Cancers are often thought to be selectively neutral. This is because most of the individuals that they kill are post-reproductive. Some cancers, however, kill the young and so select for anticancer adaptations that reduce the chance of death. These adaptations could reduce the somatic mutation rate or the selective value of a mutant clone of cells, or increase the number of stages required for neoplasia. New theory predicts that cancer selection--selection to prevent or postpone deaths due to cancer--should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.

The FVB/N mouse strain was created in the early 1970s and has since been used extensively in transgenic research because of its well-defined inbred background, superior reproductive performance, and prominent pronuclei of fertilized zygotes, which facilitate microinjection of DNA. Little is known, however, about the survivability and spontaneous disease of nontransgenic FVB/N mice. Therefore, the purpose of this study was to determine survival to 24 mo of age and the incidence of neoplastic and nonneoplastic disease at 14 and 24 mo of age. At 14 mo of age, the incidence of tumor-bearing mice was 13% in males (n = 45) and 26% in females (n = 98). All tumors in males and most in females at this time were alveolar-bronchiolar (AB) neoplasms of the lung. Survival to 24 mo of age was approximately 60% in both sexes (29/50 males, 71/116 females), and the incidence of mice with tumors at this time was 55% in males and 66% in females. In decreasing order of frequency, the following neoplasms were observed in > 5% of subjects: in males, lung AB tumors, liver hepatocellular tumors, subcutis neural crest tumors, and Harderian gland adenomas; in females, lung AB tumors, pituitary gland adenomas, ovarian tumors (combined types), lymphomas, histiocytic sarcomas, Harderian gland adenomas, and pheochromocytomas. Compared with other mouse strains, the observed incidences of tumors in FVB/N mice suggest a higher than usual rate of lung tumors and a lower than usual incidence of liver tumors and lymphomas. This tumor profile should be considered in the interpretation of neoplastic phenotypes in FVB/N-derived transgenic lines.

Sixty-three pediatric patients with germ cell tumors are presented with details of symptoms, histological findings, staging, serological markers, treatment, and response to therapy. The primary sites were: ovarian 32, testicular 17, presacral 7, mediastinal 3, intraabdominal 2, vaginal 1, and right inguinal canal 1. These patients were treated with T2 (sequential use of dactinomycin, doxorubicin, vincristine, and cyclophosphamide, with or without radiation), T6 (combination chemotherapy with cyclophosphamide, bleomycin, dactinomycin, doxorubicin, methotrexate, vincristine), or VAB treatment protocols (velban, dactinomycin, bleomycin, cisplatin). The cure rate for stage I ovarian and testicular germ cell tumors was 100%; for stage III, all primary sites, 82% and for stage IV, all primary sites, 75%. Histology was prognostic in ovarian tumors of the immature malignant teratoma type; the neural type immature teratoma, grades II and III, had the worst prognosis. Initial debulking surgery in combination with chemotherapy and radiation plays an important role in germ cell tumors. Stages II, III, and IV germ cell tumors require aggressive treatment with surgery, radiation, and chemotherapy. For stage I patients, with primary ovarian malignant tumor, cure with surgery alone can be achieved in 50% of the cases and in testicular tumors in about 70% of the patients. For those with stage I and elevated serological markers, it is feasible to follow these markers and give no treatment until there is evidence of persistent elevation or a rise in titers after an initial fall. In those without elevated serological markers, one should take into consideration the size of the tumor and the histological type before taking the "wait and see" approach. These stage I tumors are highly curable when they first present but, if allowed to recur, chemotherapy may not offer the patient such a favorable response and cure rate.

We undertook a retrospective study of 594 consecutive diagnosis by frozen section. Clinically important discrepancies were found between the frozen section and final diagnoses in 18 (3%), and unimportant discrepancies in 35 (6%). The reasons for the discrepancies were misinterpretation in 22 (41%), the presence of focal lesions in 29 (55%), and technical errors in 2 (4%). There were 4 false positive and 18 false negative diagnoses, giving a sensitivity of 93% and a specificity of 99%. Diagnoses from frozen sections were deferred in 40 cases (7%). These results are in accordance with those of similar studies, and confirm that frozen section is a highly accurate, but not infallible, method of rapid histological diagnosis.

Hamsters of three types designated as inbred cream (Epp/e/e), linebred white (EPP/cdcd/RB/A), and linebred albino (EPP/cdcde/e) were thoroughly examined histopathologically for spontaneous diseases. All hamsters were maintained simultaneously for life under identical standard laboratory conditions. Marked differences were found in longevity of the animals and in incidence, sites, patterns, and types of spontaneous diseases. In cream hamsters (CH), survival time was shorter than in white hamsters (WH) and albino hamsters (AH). More tumors and malignant lesions unrelated to survival were found in AH compared to CH and WH; also, the multiplicity of neoplasms were more pronounced in AH. The predominating tumor types differed in each line: Pancreatic islet cell neoplasms were most common in CH, adrenal gland tumors predominated in WH, and thyroid gland tumors in AH. Also, the relative incidence of spontaneous tumors varied among the lines. Some tumors seemed strain-specific and were not seen in other lines; malignant melanomas, for example, occurred only in CH and WH. Certain neoplasms, e.g., those of the thyroid and adrenal glands, were found more often in one sex than the other. The three hamster groups differed also in nonneoplastic diseases. Detailed histopathologic findings are presented and compared with data on the Syrian golden hamster, the ancestral line of these three groups.

Conditional five-year relative survival rates were calculated for patients diagnosed during 1950-1959 to examine long-term survival patterns for some of the more frequently occurring cancers. The data on the patients studied were collected as part of the national cancer institute's End Results Program. Breast cancer patients with localized disease were found to have only slightly increasing conditional rates for 20 years subsequent to diagnosis beginning at 85% at diagnosis and exceeding 90% at 20 years subsequent to diagnosis. Conditional five-year rates for patients with distant involvement approached the conditional rates for patients with regional involvement 15 years after diagnosis. Conditional rates by stage for patients with cancer of the cervix or cancer of the corpus increased initially and then became somewhat constant at a level related to stage of disease at diagnosis. For cancer of the colon, the conditional rates for female patients in each stage of disease category approached the same value 7-8 years subsequent to diagnosis. These observations may provide additional insight into the biological behavior of these cancers.

The clinical records of 1,071 cases of extrathoracic malignant neoplasms seen over a 2 year period sere reviewed: 163 had abnormal chest films, and 25 of these showed evidence of mediastinal and/or hilar lymph node metastases. The primary malignancies which metastasized to intrathoracic lymph nodes included eight tumors of the head and neck, 12 genitourinary malignancies, three carcinomas of the breast, and two malignant melanomas. The chest films were analyzed to determine the distribution of lymph node groups involved. Unilateral lymph node enlargement occurred in eight. The most frequently detected lymph node group was the right paratracheal chain (60%), while the subcarinal and posterior mediastinal groups were rarely affected. Of the 25 cases, 10 had radiographic evidence of hematogenous or lymphangitic metastases in addition in the lungs. Metastatic disease from extrathoracic neoplasms should always be considered in the differential diagnosis of hilar and mediastinal adenopathy.

The effect of epidermal growth factor (EGF) on the in vitro growth of 186 malignant human tumor specimens (45 melanomas, 32 sarcomas, and 56 lung, 16 gynecological, 14 breast, 12 genitourinary, and 11 gastrointestinal carcinomas) was evaluated in the cellular adhesive matrix human tumor culture system supplemented with transferrin, insulin, hydrocortisone, and estradiol. EGF increased tumor growth by at least 50% in 81% of the 186 tumors and by over 100% in 54%. The enhanced growth induced by EGF was related to an accelerated cellular division independent of tumor type and not to an increase in the actual number of clonogenic units. The drug concentrations of cell cycle-independent Adriamycin and cisplatin needed to achieve a 90% tumor cell kill were not altered by the responsiveness of the tumor to EGF.