A 51-Year-Old Woman With Progressive Dyspnea and Diffuse Bilateral Pulmonary Nodules.

CASE PRESENTATION: A 51-year-old woman was referred to our hospital with progressive dyspnea on exertion for 2 months after COVID-19 vaccination (ChAdOx1-S [recombinant] vaccine). She did not have a cough, fever, hemoptysis, weight loss, or night sweats. She had no history of arthritis, rash, photosensitivity, or other signs of autoimmune disease. Chest radiograph revealed diffuse ground-glass opacities and bilateral pulmonary nodules. She denied any history of smoking, contact with individuals infected with TB, relevant hobbies, or exposure to domestic animals. She had no relevant medical history, was previously healthy, and worked as a chef.

An investigation into tumor regression grade as a parameter for locally advanced rectal cancer and 5-year overall survival rate.

PURPOSE: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by surgery. Several parameters are associated with patient survival in LARC. One of these parameters is tumor regression grade (TRG); however, the significance of TRG remains controversial. In this study, we aimed to examine the correlations of TRG with 5-year overall (OS) and relapse-free survival (RFS) and identify other factors that influence the survival rates in LARC after nCRT followed by surgery. METHODS: This retrospective study included 104 patients diagnosed with LARC who underwent nCRT followed by surgery at Songklanagarind Hospital from January 2010 to December 2015. All patients received fluoropyrimidine-based chemotherapy at a total dose of 45.0 to 50.4 Gy in 25 daily fractions. Tumor response was evaluated using the 5-tier Mandard TRG classification. TRG was categorized into good (TRG 1-2) and poor (TRG 3-5) responses. RESULTS: TRG (classified by either the 5-tier classification system or the 2-group classification system) was not correlated with 5-year OS or RFS. The 5-year OS rates were 80.0%, 54.5%, 80.8%, and 67.4% in patients with TRG 1, 2, 3, and 4, respectively (P=0.22). Poorly differentiated rectal cancer and systemic metastasis were associated with poor 5-year OS. Intraoperative tumor perforation, poor differentiation, and perineural invasion were correlated with inferior 5-year RFS. CONCLUSION: TRG was probably not associated with either 5-year OS or RFS; however, poor differentiation and systemic metastasis were strongly associated with poor 5-year OS.

Ovarian steroid cell tumor (not otherwise specified) with subsequent spontaneous pregnancy after tumor removal: a case report and literature review.

Steroid cell tumors not otherwise specified are rare sex cord-stromal tumors of the ovary that may produce various steroids and are associated with hirsutism and virilization. We report a rare case of ovarian steroid cell tumor with subsequent spontaneous pregnancy after tumor removal. A 31-year-old woman presented with secondary amenorrhea, hirsutism, and inability to conceive. Clinical and diagnostic evaluations revealed a left adnexal mass and elevated serum total testosterone and 17α-hydroxyprogesterone levels. She underwent a left salpingo-oophorectomy, and histopathological examination confirmed the diagnosis of a steroid cell tumor not otherwise specified. Her serum total testosterone and 17α-hydroxyprogesterone normalized one month after surgery. Her menses resumed spontaneously one month after the operation. She spontaneously conceived 12 months after the surgery. The patient had an uncomplicated pregnancy and delivered a healthy male infant. In addition, we reviewed the literature on steroid cell tumors not otherwise specified with subsequent spontaneous pregnancies after surgery and data regarding pregnancy outcomes.

An evaluation of the association between radiological parameters and survival outcomes in pediatric patients with hepatoblastoma.

BACKGROUND: We evaluated the survival outcomes following hepatic resection as a treatment modality in pediatric patients with hepatoblastoma at a single institution, and to identify radiological parameters associated with poorer survival outcomes. METHODS: This was a retrospective cohort study. Medical records were reviewed, pertaining to pediatric patients diagnosed with hepatoblastoma who underwent surgical resection at a university hospital in Thailand between 2004 and 2021. Radiological parameters, clinical factors, and pathological data were also collected. Survival analysis was performed, and prognostic factors were identified using logistic regression analysis. RESULTS: Forty-two suitable patients were identified. Three cases with incomplete data were excluded, resulting in 39 cases being analyzed. Except for two, all patients received preoperative chemotherapy following the Thai Pediatric Oncology Group regimen. The two- and five-year overall survival rates were 78.0% and 70.9%, respectively. Upon analysis, the radiological parameters associated with poorer survival were poor response to neoadjuvant chemotherapy, presence of metastasis, post-chemotherapy tumor diameter, Post treatment extent of disease (POSTTEXT) Stage IV disease, presence of portal vein involvement, and presence of residual disease; poor neoadjuvant-response, portal vein involvement, and metastasis were independently associated with worse outcomes. In patients with non-metastatic hepatoblastoma who had at least a 25% reduction in size following neoadjuvant chemotherapy, the 5-year survival rate was 90.9% (95% CI 50.8-98.6%). CONCLUSIONS: Although preoperative evaluation of the tumor extent staging did not significantly affect survival, portal vein involvement as per POSTTEXT staging, stable or increasing tumor size, and metastasis following neoadjuvant chemotherapy were associated with poor overall survival. LEVEL OF EVIDENCE: IIB.

Optical diagnosis by near-focus versus normal-focus narrow band imaging colonoscopy in colorectal polyps based on combined NICE and WASP classification: a randomized controlled trial.

BACKGROUND/AIMS: Narrow Band Imaging (NBI) International Colorectal Endoscopic (NICE) and Workgroup Serrated Polyps and Polyposis (WASP) classifications were developed for optical diagnosis of neoplastic and sessile serrated polyps, respectively. Near-focus NBI with NICE combined with WASP criteria for optical diagnosis of colonic polyps has not yet been evaluated. We aimed to compare the accuracy of near-focus NBI (group A) with normal-focus NBI (group B) in real-time optical diagnosis of colorectal polyps using combined NICE and WASP criteria. METHODS: Among 362 patients, 118 with 227 polyps were recruited. Groups A and B included 62 patients with 130 polyps (three lost polyps) and 56 patients with 106 polyps (six lost polyps), respectively. Optical diagnoses were compared with pathological reports. RESULTS: The accuracy of optical diagnosis of neoplastic polyps in groups A and B was not significantly different (76% vs. 71%, p=0.52). WASP criteria provided all false positive diagnoses of sessile polyps as serrated polyps in 31 (16.2%) patients. CONCLUSION: Near-focus NBI was not superior to normal-focus NBI in optical diagnostics of neoplastic polyps using NICE criteria. In our study, WASP classification yielded all false positives in the diagnosis of sessile serrated adenomas/polyps. Routine real-life optical diagnosis of polyps is still unadvisable.

Risk Factors Associated with Malignant Transformation of Astrocytoma: Competing Risk Regression Analysis.

Background Malignant transformation (MT) of low-grade astrocytoma (LGA) triggers a poor prognosis in benign tumors. Currently, factors associated with MT of LGA have been inconclusive. The present study aims to explore the risk factors predicting LGA progressively differentiated to malignant astrocytoma. Methods The study design was a retrospective cohort study of medical record reviews of patients with LGA. Using the Fire and Gray method, the competing risk regression analysis was performed to identify factors associated with MT, using both univariate and multivariable analyses. Hence, the survival curves of the cumulative incidence of MT of each covariate were constructed following the final model. Results Ninety patients with LGA were included in the analysis, and MT was observed in 14.4% of cases in the present study. For MT, 53.8% of patients with MT transformed to glioblastoma, while 46.2% differentiated to anaplastic astrocytoma. Factors associated with MT included supratentorial tumor (subdistribution hazard ratio [SHR] 4.54, 95% confidence interval [CI] 1.08-19.10), midline shift > 1 cm (SHR 8.25, 95% CI 2.18-31.21), and nontotal resection as follows: subtotal resection (SHR 5.35, 95% CI 1.07-26.82), partial resection (SHR 10.90, 95% CI 3.13-37.90), and biopsy (SHR 11.10, 95% CI 2.88-42.52). Conclusion MT in patients with LGA significantly changed the natural history of the disease to an unfavorable prognosis. Analysis of patients' clinical characteristics from the present study identified supratentorial LGA, a midline shift more than 1 cm, and extent of resection as risk factors associated with MT. The more extent of resection would significantly help to decrease tumor burden and MT. In addition, future molecular research efforts are warranted to explain the pathogenesis of MT.

Juvenile Hyaline Fibromatosis: Report of a Case with a Novel ANTXR2 Gene Mutation.

BACKGROUND Juvenile hyaline fibromatosis is a rare autosomal recessive disorder with unknown prevalence characterized by abnormal development of hyalinized fibrous tissue usually in the skin, mucosa, bone, and often the internal organs. Here, we report the case of a 7-year-old girl from a family with ANTXR2 mutation confirming JHF. CASE REPORT The girl presented with multiple painless soft-tissue swellings affecting the ears, forehead, and scalp. Excisional biopsies of the masses reported positive immunohistochemical staining for collagen type VI in the extracellular matrix area, which indicated collagen VI accumulation. Genetic analysis was performed using whole-exome sequencing. The variants were further validated using Sanger sequencing in trio-based approach. We identified a novel mutation, c.1273_1293delinsTCTTGTGGGTTTGGCT in exon 15 of ANTXR2 gene, leading to a frameshift of the amino acid from codon 425 to all the rest of the amino acid chain (p.Pro425Serfs). The change of an encoded protein interrupted lysosome-mediated degradation of collagen VI. This finding was compatible with her parents whose genetic tests were both positive for the same heterogenous deletion/insertion mutation. The patient was treated with surgical excision of the tumor masses, which had to be repeated several times due to recurrences. CONCLUSIONS This novel mutation in exon 15 of the ANTXR2 gene may help improve understanding of genotype-phenotype correlations for this syndrome and provide the basis for diagnostic testing. A multidisciplinary team approach including genetic molecular testing is required for an accurate diagnosis and management of JHF for conducting genetic counseling for affected families as a part of holistic management.

Metastatic Primary Testicular Neuroendocrine Carcinoma Associated with Somatic Malignant Transformation of Teratoma: A Rare Case Report.

Testicular neuroendocrine tumor associated with teratoma is a rare disease. Very few cases have been reported in the literature, particularly cases involving visceral metastasis. Teratoma with somatic malignant transformation (SMT) is associated with a worse prognosis compared to teratoma without SMT. Previous data have suggested that chemotherapy regimens should be directed toward the transformed histology; however, those suggestions were based on patients with rhabdomyosarcoma, adenocarcinoma, and primitive neuroectodermal subtypes. To the best of our knowledge, only 2 cases with visceral metastasis have been reported, and a better outcome with the bleomycin/etoposide/cisplatin regimen, which responds strongly to germ cell tumors, has been reported in these cases. In contrast, 2 others with lymph node metastasis did not respond to these regimens. Here, we report a case of a patient with testicular neuroendocrine carcinoma associated with teratoma who achieved a good response to chemotherapy.

Prognostic Impact of the Combination of MGMT Methylation and TERT Promoter Mutation in Glioblastoma.

Background The concept of combinational analysis between the methylation of O 6 -methylguanine-DNA methyltransferase ( MGMT ) and telomerase reverse transcriptase promoter ( pTERT ) mutation in glioblastoma (GBM) has been reported. The main study objective was to determine the prognosis of patients with GBM based on MGMT/pTERT classification, while the secondary objective was to estimate the temozolomide effect on the survival time of GBM with MGMT/pTERT classification. Methods A total of 50 GBM specimens were collected after tumor resection and were selected for investigating MGMT methylation and pTERT mutation. Clinical imaging and pathological characteristics were retrospectively analyzed. Patients with MGMT/pTERT classification were analyzed using survival analysis to develop the nomogram for forecasting and individual prognosis. Results All patients underwent resection (total resection: 28%, partial resection: 64%, biopsy: 8%). Thirty-two percent of all cases received adjuvant temozolomide with radiotherapy. Sixty-four percent of the case was found methylated MGMT , and 56% of the present cohort found pTERT mutation. Following combinational analysis of biomarkers, results showed that the GBMs with methylated MGMT and wild-type pTERT had a superior prognosis compared with other subtypes. Using Cox regression analysis with multivariable analysis, the extent of resection, postoperative chemoradiotherapy, MGMT/pTERT classification were associated with a favorable prognosis. Hence, a web-based nomogram was developed for deploying individual prognostication. Conclusions The interaction of MGMT methylation and pTERT mutation was confirmed for predicting prognosis. The results from the present study could help physicians create treatment strategies for GBM patients in real-world situations.

Impact of immunohistochemistry-based subtyping of GATA3, CK20, CK5/6, and CK14 expression on survival after radical cystectomy for muscle-invasive bladder cancer.

Molecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, standard subtyping based on transcriptomic analysis is relatively expensive. This study tried to use immunohistochemistry (IHC) to subtype MIBC based on GATA3, CK20, CK5/6, and CK14 protein expression. The IHC-based subtypes in MIBC subtypes were classified as luminal (GATA3+ CK5/6-, 38.6%), basal (GATA3-CK5/6+, 12.9%), mixed (GATA3+ CK5/6+, 37.9%), and double-negative (GATA3-CK5/6-, 10.6%) in 132 MIBC patients. All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy. The mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. Only GATA3 and CK5/6 were significantly associated with survival outcome (p values = 0.004 and 0.02). The mixed subtype was significantly better in 5-year OS at 42.8%, whereas the double-negative subtype had the worst prognosis (5-year OS 7.14%). The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71-6.32). Subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy.

Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma.

Background Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA). Objective The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages. Methods Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT. Results Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose-response relationship (Mann-Whitney's U test, p = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test. Conclusion In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.

Serum ß-2 microglobulin levels are associated with distant metastasis in patients with breast cancer.

Serum ß-2 microglobulin (ß2-M) levels have been identified to be higher in patients with cancer than in healthy individuals. The aim of the present study was to evaluate the association between serum ß2-M levels and clinicopathological characteristics of patients with breast cancer in a prospective cohort study, and to evaluate the effect of ß2-M on cancer cell migration in vitro. Serum samples from 200 female patients with histologically confirmed invasive breast cancer were collected between 2017 and 2019. Their clinicopathological information was obtained and analyzed. The ß2-M levels were identified to be associated with age, histologic subtype and metastatic status. When the diagnostic association of ß2-M and metastatic status was analyzed, the area under the receiver operating characteristic curve was 0.78. Using a cut-off serum ß2-M level of 1.9 µg/ml, the sensitivity for diagnosing metastatic status was 87.5%, the specificity was 65.0%, and the diagnostic odds ratio was 2.47. Upon age stratification, the association between the ß2-M level and metastatic status was significant only in the group aged >55 years. In survival analysis, ß2-M levels >1.9 µg/ml were associated with a poor survival outcome. In vitro, the MCF-7 breast cancer cell line exhibited increased cellular migration following treatment with 30 µg/ml ß2-M. Serum ß2-M may be a predictor of metastatic status in breast cancer.

Risk Factors Associated with Malignant Transformation of Astrocytoma: Competing Risk Regression Analysis.

BACKGROUND: Malignant transformation (MT) of low-grade astrocytoma (LGA) triggers a poor prognosis in benign tumors. Currently, factors associated with MT of LGA have been inconclusive. The present study aims to explore the risk factors predicting LGA progressively differentiation to malignant astrocytoma. MATERIALS AND METHODS: The study design was a retrospective cohort study of medical record reviews of patients with LGA. Using the Fire and Grey method, the competing risk regression analysis was performed to identify factors associated with MT, using both univariate and multivariable analyses. Hence, the survival curves of the cumulative incidence of MT of each covariate were constructed following the final model. RESULTS: Ninety patients with LGA were included in the analysis, and MT was observed in 14.4% of cases in the present study. For MT, 53.8% of patients with MT transformed to glioblastoma, while 46.2% differentiated to anaplastic astrocytoma. Factors associated with MT included supratentorial tumor (subdistribution hazard ratio [SHR] 4.54, 95% CI 1.08-19.10), midline shift >1 cm (SHR 8.25, 95% CI 2.18-31.21), nontotal resection as follows: Subtotal resection (SHR 5.35, 95% CI 1.07-26.82), partial resection (SHR 10.90, 95% CI 3.13-37.90), and biopsy (SHR 11.10, 95% CI 2.88-42.52). CONCLUSION: MT in patients with LGA significantly changed the natural history of the disease to an unfavorable prognosis. Analysis of patients' clinical characteristics from the present study identified supratentorial LGA, a midline shift more than 1 cm, and extent of resection as risk factors associated with MT. The more extent of resection would significantly help to decrease tumor burden and MT. In addition, future molecular research efforts are warranted to explain the pathogenesis of MT.

Accuracy of high-resolution rectal magnetic resonance imaging re-staging with histopathology in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND/OBJECTIVE: Re-staging of locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (NCRT) is a crucial step in surgical decision-making. Currently, MRI is the imaging of choice for evaluation of LARCs, however, the diagnostic accuracy of this modality is inconsistent. In this study, we evaluated the diagnostic accuracy of MRI in LARC and analyzed the factors that influenced the accuracy. METHODS: The records of 133 patients diagnosed with LARC who were operated on during 2011-2018 were retrospectively reviewed. All patients received NCRT followed by re-staging based on high-resolution rectal MRI. The MRI results were analyzed for their yT and yN accuracy and anal sphincter involvement and compared with the related histopathological studies after definitive surgery. RESULTS: Re-staging MRIs gave overall accuracy in both the yT stage and yN evaluation of 85% (K 0.45 and 0.21, respectively). The MRI tended to overstaging for tumor invasion and understaging for lymph node involvement (sign test p-values = 0.017 and 0.022, respectively.) The highest accuracy of the yT stage was yT4b (93%, K 0.71). The study found that larger tumors (>3 cm) were associated with significantly higher accuracy in the yT readings while lack of lymphovascular invasion was associated with higher accuracy in the yN readings. The negative predictive value for anal sphincter involvement was 100%. CONCLUSION: MRI has limited accuracy in post-NCRT re-staging in LARC, tending to give overstaged yT readings and understaged yN readings. An MRI exclusion of sphincteric involvement is highly reliable.

The clinical characteristics and prognostic factors of multiple lesions in glioblastomas.

OBJECTIVE: Multiple glioblastomas (GBM) are the uncommon presentation of the disease. We aimed to identify the variables associated with the survival of patients with multiple GBMs according to the updated WHO classification. PATIENTS AND METHODS: We retrospectively reviewed 173 patients with newly diagnosed GBM between January 2003 and December 2018 and analyzed patients with multiple lesions at the time of diagnosis. The clinical, radiographic, and biomarkers were evaluated for descriptive analysis. The median overall survival and the Kaplan-Meier curves of the multiple GBMs were estimated. Furthermore, the Cox proportional hazard regression was the estimated hazard ratio for death according to various factors. Moreover, Schoenfeld's global test was performed for estimating assumptions. RESULTS: Of these, 30 (17.3%) of all GBMs were multiple GBMs, and multifocal and multicentric GBMs were found in 27 (90%) and 3 (10%), respectively. The median survival of the multiple GBMs was significantly shorter than solitary GBM (6 vs. 12 months, p = 0.003). Using Cox proportional hazards regression, the independent prognostic factors of multiple GBMs were concomitant Temozolomide with radiotherapy, wild-type IDH1, methylated MGMT promoter methylation in univariate analysis. In multivariable analysis, concomitant Temozolomide (TMZ) with radiotherapy (RT) was the strongest predictor associated with prognosis in multiple GBMs (0.40, 95%CI 0.16-0.97). CONCLUSIONS: Multiple lesions are uncommon findings in glioblastoma with poor prognostic features. Concomitant TMZ with RT was the strongest predictor of prognosis. In the future., IDH1 mutation and MGMT promoter methylation should be further explored as prognostic factors.

Giant intraventricular and paraventricular cavernous malformations with multifocal subependymal cavernous malformations in pediatric patients: Two case reports.

BACKGROUND: Giant cavernous malformation (GCM) is rarely found in intraventricular or paraventricular locations. CASE SUMMARY: We present two cases of 6-mo and 21-mo boys with intraventricular and paraventricular GCMs including a literature review focused on location and imaging findings. Characteristic magnetic resonance imaging findings such as multicystic lesions and a hemosiderin ring or bubbles-of-blood appearance can assist in the differential diagnosis of a hemorrhagic intraventricular and/or paraventricular mass. CONCLUSION: Multifocal intraventricular and/or paraventricular GCM in small children is rare. The characteristic magnetic resonance imaging findings can help to differentiate GCMs from other intraventricular tumors.

Glioblastoma Multiforme Associated with Arteriovenous Malformation: A Case Report and Literature Review.

Although microvascular proliferation can be observed in glioblastoma, obvious vascularity coupled with coexisting cerebral arteriovenous malformation (AVM) is extremely rare. This report is of a rare case of glioblastoma, coexisting with a cerebral AVM. A 20-year-old male presented with progressive right hemiparesis within 1 month. Cranial magnetic resonance imaging revealed a large bleeding tumor with surrounding dilated vessels. Cerebral angiography demonstrated a left frontal AVM with a 1.2 cm nidus. The patient underwent preoperative embolization and radical resection. The coincidence of glioma and AVM was a rare association. However, the concept of hypervascular glioblastoma has been used in different states from different literature reviews; therefore, the role of proangiogenic factors should be addressed.

Multiple, Primary Brain Tumors with Diverse Origins and Different Localizations: Case Series and Review of the Literature.

BACKGROUND: Multiple, primary brain tumors with different histological types occurring in the same patient are extremely rare. Several hypotheses have been proposed, and the pathophysiology of coexisting tumors has long been debated; however, due to low incidence, standard practices for this scenario are still inconclusive. CASE DESCRIPTION: The authors describe 6 cases of coexisting tumors. By conducting a literature research focused on the computed tomography (CT) era and patients without prior radiation or phakomatosis. Sixty-five such reported cases were identified. In addition, the authors summarize their experience in 6 patients including histopathological features, chronological presentations, outcomes, mortality, and management from their series as well as from previous cases from the reported literature. CONCLUSION: The coexistence of multiple, primary brain tumors is an interesting condition. Surgical management remains the major treatment; malignant histology has a poor prognostic factor.

Survival and Prognostic Factors in Pediatric Patients with Medulloblastoma in Southern Thailand.

BACKGROUND: The current prognosis of medulloblastoma in children is better because of technological advancements and improvements in treatment strategies and genetic investigations. However, there is a lack of studies that focus on medulloblastoma in Thailand. The aims of our study were to conduct a survival analysis and to identify the prognostic factors of pediatric medulloblastoma. MATERIALS AND METHODS: Fifty-five children, with medulloblastoma, were eligible for analysis between 1991 and 2015. We retrospectively reviewed both the clinical and the histological data. Survival curves were constructed using the Kaplan-Meier method. For comparisons of dichotomous factors, between groups, the log-rank test was used to determine survival. The Cox proportional hazard regression model was used to identify the univariate and multivariate survival predictors. RESULTS: The mortality rate was 49.1% in this study. The median follow-up time was 68.8 months (range: 1-294 months). The 5-year overall survival rate and median survival time were 53.8% (95% CI 38.7-66.7) and 80 months (95% CI 23-230), respectively. Univariate analysis revealed children <3 years of age, hemispheric tumor location, high risk according to risk stratification, and patients who did not receive radiation therapy affected the prognosis. In multivariable analysis, hemispheric tumors (hazard ratio [HR] 2.54 [95% CI 1.11-5.80]; P = 0.01)and high risk groups (HR 3.86 [95% CI 1.28-11.60]; P = 0.01) influenced death. Finally, using conditional inference trees, the study showed that hemispheric tumor locations are truly aggressive in behavior, whereas risk stratification is associated with the prognosis of midline tumors. CONCLUSIONS: Hemispheric medulloblastoma and high-risk groups according to risk stratification were associated with poor prognosis.

Molecular dynamic simulation of mutated ß-catenin in solid pseudopapillary neoplasia of the pancreas.

Solid pseudopapillary neoplasia of the pancreas (SPN) is a rare pancreatic neoplasm that frequently harbors mutations in catenin ß1 (CTNNB1, encoding ß-catenin) as a part of its molecular pathogenesis. Mutations to CTNNB1 reported in SPN usually occur at the serine/threonine phosphorylation sites, including codons 33, 37 and 41, and the flanking residues of codon 33. On analysis of 3 cases of SPN, mutations to CTNNB1 were detected in codon 32 (D32A and D32Y). As this residue, aspartic acid, is not a direct phosphorylation site of the protein, molecular modeling tools were used to predict the influence of these mutations on the protein structure of ß-catenin. A total of three MD simulations (wild-type, D32A, and D32Y) were performed to visualize the conformations of ß-catenin under in vivo, aqueous-phase conditions at 37°C. In the wild-type protein, the secondary structure of residues P16-H28 remained helical; we therefore hypothesized that the helical structure of this protein fragment (residues M11-G50) was necessary for phosphorylation of S33 phosphorylation. The loss of the secondary structure in P16-H28 was observed in D32A, losing its helical structure and becoming a turn; however, in the D32Y mutant, the helical structure remained. The present demonstrated that structural changes in the mutated ß-catenin protein at D32 could potentially explain the mechanism behind its defective phosphorylation in the pathogenesis of SPN.