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PurposeOvarian carcinoma (OC) is the most lethal female genital cancer. After a primary curative surgical approach followed by chemotherapy, a fraction of the patients recur with chemoresistant disease. Data indicate a favorable therapeutic effect of tumor-infiltrating neutrophils (TIN) in OC. Our aim was to investigate the prognostic role of CD66b expression, corresponding to neutrophilic infiltration for recurrence-free survival (RFS) and overall survival (OS) in patients with OC.MethodsA collective of 47 primary serous ovarian carcinoma and their matching recurrences were processed and stained with CD66b using immunohistochemistry. Tumors from patients with RFS of more than 6 months were defined as chemosensitive. Statistical analysis of CD66b expression was performed to assess the clinical endpoints.ResultsHigh density of CD66b expressing neutrophils in primary carcinoma was associated with chemosensitivity (p = 0.014) and longer RFS (p = 0.001). Univariate analysis identified high density of CD66b expressing neutrophils as a predictor for favorable RFS (HR 0.41, 95% CI 0.22–0.76, p < 0.005). Residual disease > 2 cm (HR 3.67, 95% CI 1.62–8.31, p < 0.002) and higher number of chemotherapy cycles (HR 1.28, 95% CI 1.05–1.55, p < 0.013) were associated with worse RFS. Multivariate analysis showed that high density of CD66b expressing neutrophils (HR 0.22, 95% CI 0.10–0.48, p < 0.001) and residual disease > 2 cm (HR 3.69, 95% CI 1.43–9.53, p < 0.007) were independent predictors of RFS but had no impact on OS.ConclusionHigh CD66b neutrophil density in primary high-grade OC predicts good response to initial chemotherapy and longer recurrence-free survival independent of known risk factors.

Background Ovarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC. Methods A tissue microarray of biopsies of mostly high-grade primary serous OC and matched recurrences of 47 patients was stained with OX40. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance. Results Chemosensitivity correlated significantly with high OX40 positive immune cell density in primary cancer biopsies ( p =  0.027). Furthermore patients with a higher OX40 expression in recurrent cancer biopsies showed a better outcome in recurrence free survival (RFS) ( p =  0.017) and high OX40 expression was associated with chemosensitivity ( p =  0.008). OX40 positive TICI in recurrent carcinomas significantly correlated with IL-17 positive tumor infiltrating immune cells in primary carcinomas ( r s  = 0.34; p  = 0.023). Univariate cox regression analysis revealed a significant longer RFS and higher numbers of chemotherapy cycles for high OX40 tumor cell expression in recurrent cancer biopsies (HR 0.39, 95%CI 0.16–0.94, p = 0.036 and 1.28, 95%CI 1.05–1.55; p = 0.013 ). Conclusion High OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy.

Background Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS). Methods A tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS. Results Patients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years ( p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years ( p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate ( p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193). Conclusions To the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. Highlights • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.

Small-cell carcinoma of the pancreas (PSCC) is a highly aggressive neoplasia with a dismal prognosis. It is extremely rare, with only a few cases reported in the literature. There is a paucity of clinical data to guide management and since the disease is mainly diagnosed at an advanced stage standard treatment consists of chemotherapy based upon treatment protocols used for small-cell lung cancer. We report the case of a female diagnosed with PSCC who achieved complete clinical remission after treatment with carboplatin and etoposide. During a 3-year follow-up the patient developed a gallbladder adenocarcinoma that was treated by surgical resection but relapsed within 20 months with widespread hematogenous metastasis.

The positive rate of RT-PCR for nasopharyngeal samples was reported to be 63% in early stage of COVID-19, therefore, a significant number of patients may have false negative results.4 Previous data from SARS-CoV infections showed that RNA levels first peaked in upper respiratory tract but remained higher in lower respiratory tract specimens 3 weeks after onset of illness.4 The same may be also expected with COVID-19 infections.5 6 Detection of early cytomorphological changes in the lung from bronchial fluid or BAL may, therefore, help with timely start of COVID-19 surveillance and supportive therapy. In MERS-CoV infections, multinucleate syncytial cells, some of them with prominent eosinophilic nucleoli, were also described.7 It was suspected that multinucleated epithelial cells, pneumocytes and bronchial submucosal gland cells are the main targets in MERS-CoV infection.7In our case, the viropathic multinucleated giant cells were of histiocytic origin. [...]macrophages in COVID-19 infection may also be targets for COVID-19 beside pneumocytes as was described in pneumonia caused by measles,8 even though a secondary reactive non-viropathic giant cell response to the viral infection as a cause of the observed changes cannot be excluded. [...]the cytopathological detection of virus infected multinuclear macrophages in bronchial fluid or BAL might add substantial early information in COVID-19.

Background Ovarian carcinoma is the most lethal gynecologic malignancy because of its late diagnosis, extremely high recurrence rate, and limited curative treatment options. In clinical practice, high-grade serous carcinoma (HGSC) predominates due to its frequency, high aggressiveness, and rapid development of drug resistance. Recent evidence suggests that CXCL12 is an important immunological factor in ovarian cancer progression. Therefore, we investigated the predictive and prognostic significance of the expression of this chemokine in tumor and immune cells in patients with HGSC. Methods We studied a cohort of 47 primary high-grade serous ovarian carcinomas and their associated recurrences. A tissue microarray was constructed to evaluate the CXCL12 immunostained tumor tissue. CXCL12 expression was evaluated and statistically analyzed to correlate clinicopathologic data, overall survival, and recurrence-free survival. Results A high proportion of CXCL12 + positive immune cells in primary ovarian serous carcinoma correlated significantly with chemosensitivity ( p  = 0.005), overall survival ( p  = 0.021), and longer recurrence-free survival ( p  = 0.038). In recurrent disease, high expression of CXCL12 was also correlated with better overall survival ( p  = 0.040). Univariate and multivariate analysis revealed that high CXCL12 + tumor-infiltrating immune cells (TICs) (HR 0.99, p  = 0.042, HR 0.99, p  = 0.023, respectively) and combined CXCL12 + /CD66b + infiltration (HR 0.15, p  = 0.001, HR 0.13, p  = 0.001, respectively) are independent favorable predictive markers for recurrence-free survival. Conclusion A high density of CXCL12 + TICs predicts a good response to chemotherapy, leading to a better overall survival and a longer recurrence-free interval. Moreover, with concomitant high CXCL12/CD66b TIC density, it is an independent favorable predictor of recurrence-free survival in patients with ovarian carcinoma.

Endocrine therapy is an effective treatment for low-grade serous ovarian cancer. However, the role of estrogen and progesterone receptors as biomarkers for high-grade serous ovarian cancer (HGSOC) is yet to be elucidated because not all estrogen and progesterone receptor-positive tumors benefit from anti-estrogen therapy. The degree of expression is presumed to play a vital role; however, that role is not well-defined in ovarian cancer. We aimed to determine the role of estrogen and progesterone receptor expression in primary and paired relapsed HGSOC. In this study, primary and matched relapsed tumor samples were collected from 80 patients with International Federation of Gynecology and Obstetrics Stage II–IV HGSOC. Tissue microarray was conducted and immunohistochemistry for estrogen and progesterone receptor expression was performed. Two independent pathologists performed the tissue microarray analysis with the Immunoreactive Score and Allred Total score. In the paired analysis, no significant difference in estrogen receptor expression was observed. However, progesterone receptor expression was significantly lower in patients with recurrent platinum-sensitive HGSOC. We conclude that anti-estrogen therapy targeting estrogen receptor positive HGSOC could be administered in primary and relapsed settings. The use of endocrine maintenance with an aromatase inhibitor in patients with estrogen receptor positive HGSOC needs to be further evaluated and validated in a randomized controlled trial.

Follow-up is essential for the early detection of recurrent non-muscle invasive bladder cancers (NMIBC). This study investigates the clinical relevance of new diagnostic tools such as an mRNA-based urine test (XPERT© Bladder Cancer Monitor, XBCM) and Narrow Band Imaging© (NBI) and compares them with the established follow-up diagnostics (white-light cystoscopy (WLC) and urine cytology). This was a prospective, double-blind, single-center study that involved patients undergoing NMIBC screening at a tertiary care center. Enrollment occurred between January 2018 and March 2020. In addition to standard care (WLC, cytology, and ultrasound), patients underwent XBCM urine testing and NBI cystoscopy. In total, 301 WLCs were performed; through this, 49 patients demonstrated NMIBC recurrence. NBI cystoscopy was congruent with WLC in all patients. Cytology showed a sensitivity (SE) and specificity (SP) of 27% and 97% (PPV: 65%; NPV 87%), respectively, whereas XBCM showed SE and SP of 58% and 89%, respectively (PPV: 51%; NPV: 92%; AUC: 0.79 (0.716–0.871)). Subgroup analysis showed improved SE and similar SP (PPV, NPV) for high grade (HG) recurrence, with a SE of 74% and SP of 89% (39%, 97%). NBI cystoscopy does not necessarily provide additional benefit over standard WLC. However, the XBCM may provide better SE and a diagnostic advantage in instances of HG disease recurrence.

Background: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment. Methods: We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months. Results: There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS (p = 0.008) and OS (p = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity (p = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24–0.99; p = 0.047) and OS (HR = 0.28; 95% CI 0.10–0.77; p = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles. Conclusions: The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration.

Background Cancer of the ovary is mostly discovered at a late stage and cannot be removed by surgery alone. Therefore surgery is usually followed by adjuvant chemotherapy. However, few reliable biomarkers exist to predict response to chemotherapy of ovarian cancer. Previously, we could demonstrate that IL-17 density is indicative for chemosensitivity. This study focuses on the predictive value of myeloperoxidase (MPO) concerning response to chemotherapy of ovarian cancer. Methods Biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were stained with MPO after fixation in formalin and embedding in paraffin. For this staining the technique of tissue-microarray was used. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance as previously publised. Data for MPO could be analyzed in 92 biopsies. Results MPO and IL-17 positive immune cells correlated significantly in biopsies of primary and recurrent carcinomas ( r s  = 0.41; p  = 0.004 and r s  = 0.40; p  = 0.007, respectively). MPO expression alone did not predict response to chemotherapy, but in multivariate cox regression analysis including age, residual disease, number of chemotherapy cycles, FIGO classification and combined categorized MPO and IL-17 cell densities of primary cancer biopsies, the combination of both immune markers was an independent prognostic factor for recurrence-free survival ( p  = 0.013, HR = .23, 95CI = 0.07–0.73). There was no chemoresistant patient in the subgroup of MPO + IL-17+, neither in primary nor in recurrent cancer biopsies. Conclusions High MPO positive cell density enhances the indicative value of IL-17 for response to chemotherapy in ovarian carcinoma. Although, these results have to be validated in a larger cohort.