Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database.

PURPOSE: Craniopharyngiomas are rare tumors originating in the sellar region, with limited information on their somatic mutational landscape. In this study, we utilized a publicly available genomic database to profile the somatic mutational landscape of craniopharyngioma patients and interrogate differences based on histologic subtype. METHODS: We utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE)® database accessed from cBioPortal (v13.1-public) to query all patients with craniopharyngiomas. RESULTS: Of the 336 patients with sellar tumors, 51 (15.2%) had craniopharyngiomas. Of these 51 patients, 42 (82.4%) were adamantinomatous subtype and 9 (17.6%) were papillary subtype. In this cohort, 32 (62.7%) patients were pediatric, while 19 (37.3%) were adult. The top mutations in the cohort were: CTNNB1 (n = 37; 73%), BRAF (n = 7; 14%), ARID1B (n = 5; 10%), KMT2D (n = 4; 8%), FANCA (n = 4; 8%), ATM (n = 4; 8%), and TERT (n = 3; 8%). Of the 37 patients with CTNNB1 mutations, 8 (21.6%) had S33X, 9 (24.3%) had S37X, 7 (18.9%) had T41X, and 5 (13.5%) had D32X. In this cohort, CTNNB1 mutations tended to co-occur with ATM (n = 4; 10.8%), KMT2C (n = 4; 10.8%), TERT (n = 3; 8.1%), BLM (n = 3; 8.1%), and ERBB2/3 (n = 3; 8.1%), suggesting CTNNB1 mutations tended to co-occur with mutations in genes important in cell growth and survival, chromatin accessibility, and DNA damage response pathways. CONCLUSIONS: CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.

Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

Patterns of recurrence after oesophagectomy and postoperative chemoradiotherapy versus surgery alone for oesophageal squamous cell carcinoma.

BACKGROUND: Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies. METHODS: Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival. RESULTS: A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3-4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001). CONCLUSION: Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.

Central large pulmonary arteriovenous malformation with aneurysmal dilatation.

A centrally located large pulmonary arteriovenous malformation (PAVM) with aneurysmal formation is uncommon and the optimal treatment remains unclear. Here we report a 63-year-old female with a large PAVM located in the pulmonary hilum presenting with dyspnea and a brain abscess. A muscle-sparing thoracotomy with lobectomy of the left upper lobe was successfully performed under the guidance of three-dimensional reconstruction imaging of the thoracic vasculature.

Two-layer method (UW solution/perfluorochemical plus O2) for lung preservation in rat lung transplantation.

A new preservation method using perfluorochemicals (PFC) with oxygen administered continuously was developed for lung preservation and compared with traditional cold preservation methods for rat lung transplantation. Male Sprague-Dawley rats underwent orthotopic left lung transplantations of grafts preserved in lactiated Ringers solution (LR), University of Wisconsin solution (UW), Celsior solution, or a two-layer (PFC plus O2) solution for 6 hours. One hour after reperfusion, the right pulmonary artery and bronchus were clamped and 5 minutes later we recorded peak airway pressure and PaO2 level. The isograft was excised for measurement of myeloperoxidase activity, wet-to-dry ratio, and histologic examination to evaluate isograft function. The mean peak airway pressure was 29.80+/-6.72 mm H2O in the LR group, 28.80+/-5.76 mm H2O in the UW group, 33.60+/-5.17 mm H2O in the Celsior group, and 32.40+/-2.60 in the two-layer group. The mean PaO2 level was 99.78+/-76.09 mm Hg in the LR group, 87.84+/-33.58 mm Hg in the UW group, 104.50+/-72.93 mm Hg in the Celsior group, and 62.08+/-31.34 mm Hg in PFC and UW solution plus O2 group (two layers). The mean net myeloperoxidase activity OD level was 0.110+/-0.104 in the LR group, 0.392+/-0.328 in the UW group, 0.351+/-0.620 in the Celsior group, and 0.532+/-0.616 in the two-layer group. The mean wet-to-dry ratio was 7.47+/-1.60 in the LR group, 6.56+/-0.62 in the UW group, 7.54+/-2.19 in the Celsior group, and 5.32+/-2.20 in the two-layer group. The differences between groups in these parameters were not significant. Upon histologic examination, more inflammatory cell aggregates were seen in the two-layer group, less in the LR and the Celsior groups. The function of the lung graft after 6 hours of storage was not better using this two-layer method for preservation than traditional preservation methods in rat lung transplantation. Histologic examination revealed more inflammatory cell aggregates in the lung graft preserved using a two-layer method.

[Activation of the latent Toxoplasma infection and cyst formation in mice].

Latent Toxoplasma infection in mice inoculated with the low virulent Beverley strain (BEV) and avirulent Fukaya strain (FUK) was reactivated by prednisolone administration. Parasitaemia reappeared and the organism could be continuously isolated from the lymph nodes by mouse passage. No distinct decrease in specific antibody levels was observed when the sera were assayed by dye test and latex agglutination test. A significant increase in the number of brain cysts in infected mice was noted at the third week of infection while the challenge infection and steroid immunosuppression treatment resulted in an enhancement of cyst formation. A hypothesis was, therefore, proposed that the cyst formation in tissues might be regulated by the immune response of infected host to Toxoplasma infection.

[Studies on the determination of the circulating antigen in experimental toxoplasmosis].

This paper reports on the regular pattern of growth and decline of the circulating antigen (CA) determined by I-ELISA in experimentally infected rabbits. Toxoplasma antigen was demonstratable in the circulation in 64.7% rabbits 1 day after tachyzoite inoculation and the level of the CA in sera from infected rabbits showed an increase on d4 and reached its peak level on d10-13 after inoculation but declined soon thereafter. CA was not detectable on days 60 to 90 after inoculation. The results suggest that determining CA is a useful means for diagnosing active toxoplasmosis and that I-ELISA might be a promising approach to detect CA in toxoplasmosis.

Solitary fibrous tumors of the pleura: clinicopathological characteristics, immunohistochemical profiles, and surgical outcomes with long-term follow-up.

BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare. The aims of this study were (1) to characterize their clinicopathological features more precisely; (2) to determine whether an immunohistochemical (IHC) study can be helpful in distinguishing benign from malignant SFTPs; and (3) to provide more complete information to better predict prognosis. METHODS: Microscopic examinations of tumorous specimens from 15 patients were repeated and the tumors were reclassified. In addition to evaluating clinicopathological variables, expressions of p16, p53, Ki-67, CD-117, estrogen receptor (ER), and progesterone receptor (PR) biomarkers were studied and their clinicopathological and prognostic significance analyzed. RESULTS: Of the 15 enrolled patients (mean age 57 years; 8 men and 7 women), 8 were symptomatic when diagnosed. Eight patients underwent CT-guided needle biopsies before surgery and two had positive findings. All cytologic studies of pleural effusion were negative for malignant cells. Complete pleural resection with adequate safe margins was performed for all patients. Eleven cases proved to have benign tumors and 4 had malignancies. Local recurrence occurred in 3 cases and distant metastasis in one. Conventional factors, including tumor size, tumor shape, symptomatic presentation, and histological type did not affect prognosis. Interestingly, p16 expression was significantly associated with tumor recurrence ( P = 0.009). CONCLUSION: Complete pleural resection with adequate safe margins can achieve satisfactory outcomes in a majority of cases, but long-term follow-up for all patients is recommended due to the potential for late tumor recurrence. Conventional clinicopathological variables do not affect prognosis. However, IHC studies of the CD-34 and bcl-2 biomarkers can be important for further differential diagnosis, and p16 expression can be used to predict tumor recurrence.