Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed. Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006). Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

Long-Term Outcome After Histopathological Complete Response with and Without Nodal Metastases Following Multimodal Treatment of Esophageal Cancer.

BACKGROUND: This study analyzed the long-term survival after pathological complete response (pCR) with and without nodal metastases and associated recurrence following multimodal treatment of esophageal cancer. The recurrence pattern after pCR is of importance for different postoperative surveillance strategies. METHODS: A cohort of 890 patients with esophageal cancer received neoadjuvant therapy followed by transthoracic esophagectomy. Only patients with pCR of the primary tumor with and without nodal metastasis were analyzed. A clinicopathological database was set up and completed with long-term follow up information on recurrent disease. RESULTS: The specimen of 201 patients (23%) demonstrated pCR, 84% without (ypT0N0) and 16% with residual nodal disease (ypT0N+). For ypT0N0 patients, the 5-year overall survival was significantly higher than for patients with metastatic nodes (77% vs. 24%) (p < 0.0001). Sixty-eight percent of patients had no evidence of tumor recurrence, whereas 32% had proven relapse. For patients with and without tumor recurrence, 5-year survival rates were 14% and 93%, respectively (p < 0.0001). For patients with recurrent disease, median survival time was 27 for locoregional, 44 for distant, and 24 months for combined recurrence (p = 0.302). In the multivariable Cox-regression analysis, node-positive disease predicted both locoregional and metastatic recurrence. CONCLUSIONS: Pathological CR offers long-term survival in patients without nodal metastases but outcome significantly deteriorates with the presence of nodal metastases. Follow-up recommendations may therefore be adopted in patients with pCR. Furthermore, "watch-and-wait" surveillance strategies with suspected clinical complete response have to be considered with caution.

Advances in cancer immunotherapy 2019 - latest trends.

Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.

Diagnostic challenges of hemihematocolpos and dysmenorrhea in adolescents: obstructed hemivagina, didelphys or bicornuate uterus and renal aplasia is a rare female genital malformation.

OBJECTIVES: To develop a clear diagnostic and therapeutic strategy for adolescents presenting with abdominal pain and vaginal tumor caused by congenital female genital anomalies, such as blind hemivagina and uterine anomalies, as the lack of the correct diagnosis of the underlying anatomical genitourinary malformation frequently leads to destructive surgical procedures. METHODS: Retrospective study, study group: patients with double/bicornuate uterus, blind hemivagina and hematocolpos (n = 13), controls: patients with uterine malformation and complete vertical vaginal septum (n = 11), analysis for: menarche, age at onset of symptoms, type of malformation, symptoms leading to admission and diagnostic/surgical techniques applied. RESULTS: Median age at diagnosis study group 19.85 (SD ± 6.23, range 13-23 years) versus controls 26.09 years (SD ± 7.44, 16-36 years); predominance of imperforated hemivagina: 69.2 % right-sided versus 30.8 % left-sided septum; renal agenesis ipsilateral to imperforate hemivagina 100 % study group versus 9.1 % controls; 84.6 % previous surgical interventions in the study group, such as partial removal of the septum and re-obliteration, unilateral salpingo-ovarectomy and vaginal drainage of pyometra. We used a single transvaginal surgical procedure, including removal of the obstructed vaginal septum and marsupialization of the blind hemivagina. CONCLUSIONS: A diagnostic and therapeutic algorithm for young women presenting with progressive dysmenorrhea and abdominal pain and/or vaginal tumor reduces destructive interventions.