Transcriptome profiling of intact bowel wall reveals that PDE1A and SEMA3D are possible markers with roles in enteric smooth muscle apoptosis, proliferative disorders, and dysautonomia in Crohn's disease.

Background: Inflammatory bowel disease (IBD) is a complex and multifactorial inflammatory condition, comprising Crohn's disease (CD) and ulcerative colitis (UC). While numerous studies have explored the immune response in IBD through transcriptional profiling of the enteric mucosa, the subtle distinctions in the pathogenesis of Crohn's disease and ulcerative colitis remain insufficiently understood. Methods: The intact bowel wall specimens from IBD surgical patients were divided based on their inflammatory status into inflamed Crohn's disease (iCD), inflamed ulcerative colitis (iUC) and non-inflamed (niBD) groups for RNA sequencing. Differential mRNA GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes), and GSEA (Gene Set Enrichment Analysis) bioinformatic analyses were performed with a focus on the enteric autonomic nervous system (ANS) and smooth muscle cell (SMC). The transcriptome results were validated by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Results: A total of 2099 differentially expressed genes were identified from the comparison between iCD and iUC. Regulation of SMC apoptosis and proliferation were significantly enriched in iCD, but not in iUC. The involved gene PDE1A in iCD was 4-fold and 1.5-fold upregulated at qPCR and IHC compared to that in iUC. Moreover, only iCD was significantly associated with the gene sets of ANS abnormality. The involved gene SEMA3D in iCD was upregulated 8- and 5-fold at qPCR and IHC levels compared to iUC. Conclusion: These findings suggest that PDE1A and SEMA3D may serve as potential markers implicated in enteric smooth muscle apoptosis, proliferative disorders, and dysautonomia specifically in Crohn's disease.

Case Report: Systemic treatment for breast and vulvar metastases from resected rectal signet ring cell carcinoma.

Background: Breast and vulvar metastases from rectal signet ring cell carcinoma (SRCC) represent a rare and obscure clinical entity associated with poor survival. Managing patients with metastatic rectal SRCC is extremely challenging due to the absence of high-quality evidence. Case presentation: A 26-year-old woman presented with progressively worsening anal pain, constipation, and hematochezia for approximately two years. Following the diagnosis of locally advanced rectal cancer (cT3N0-1M0), she received neoadjuvant chemotherapy with modified FOLFOX6 regimen and underwent laparoscopic abdominoperineal resection. Metastases to the breast and vulva developed during postoperative chemotherapy. Genetic testing revealed RAS/BRAF wild-type and microsatellite instability (MSI)-low status. Though sequential administration of irinotecan plus tegafur and tegafur plus raltitrexed-based chemotherapy in combination with bevacizumab, the disease progressed rapidly. Sadly, the patient passed away 15 months after initial diagnosis due to rapidly progressive disease. Conclusion: Rectal SRCC is associated with younger on-set, aggressive behaviors, and worse survival outcomes. Due to poor cohesiveness, SRCC tends to develop metastases. A patient's medical history and immunohistochemical staining (such as CK20, CK7, and CDX-2) can aid in identifying the tumor origin of breast and vulvar metastases. Mutations and signaling pathways predominant in the tumorigenesis of SRCC remains unveiled. There is poor effect of conventional chemotherapies, targeted and immunotherapies for colorectal adenocarcinoma on SRCC, so novel therapies are needed to treat this patient population.

Methylprednisolone for idiopathic granulomatous mastitis: a prospective observational cohort study.

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.

Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway.

BACKGROUND: Part of papillary thyroid microcarcinoma (PTMC) has a high risk of tumor invasion and metastasis, which may occur in the regional lymph node metastasis or distant metastasis, severely threatening the life of patients. Invasion and metastasis are tightly involved in the proliferation, migration and invasion in cancer. This study aimed to investigate the role of tescalcin (TESC) in the proliferation, migration and invasion of PTMC. METHODS: The expressions of TESC in PTMC tissues and cells were detected by immunohistochemistry or qRT-PCR. Then, TPC-1 and BHT101 cells transfected with TESC-RNAi were used for the transcriptome sequencing. The proliferation, apoptosis, migration and invasion of TPC-1 and BHT101 cells were detected by CCK-8, colony formation, flow cytometric assay, transwell migration and scratch test. Moreover, TESC-RNAi transfected TPC-1 and BHT101 cells were subcutaneously injected into mice. Tumor volume and weight were calculated, and the positive rate of Ki-67 was determined by immunohistochemistry. Finally, the levels of c-Fos, ERK1/2 and p-ERK1/2 were determined by western blot. RESULTS: The expressions of TESC in PTMC tissues and cell lines were prominently enhanced. Transcriptome sequencing results showed that c-Fos was decreased in TPC-1 and BHT101 cells transfected with TESC-RNAi, which was associated with multiple different signaling pathways including the MAPK signaling pathway. Furthermore, TESC promoted the progress of PTMC by regulating the expression of c-Fos, which might be associated with the ERK signaling pathway. CONCLUSIONS: TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.

Immunoglobulin (Ig) G4-related sclerosing cholangitis in patients resected for presumed perihilar cholangiocarcinoma: a 10-year experience.

BACKGROUND: This study aimed to investigate the incidence of immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC) in patients resected for perihilar cholangiocarcinoma (PHC) in a designated hospital from 2010 to 2019. We also aimed to evaluate the diagnostic dilemma of IgG4-SC clinically. METHODS: Between January 2010 and December 2019, all patients who underwent radical resection due to presumed PHC were included. Independent pathologists scored bile duct samples based on the International Consensus Pathology Criteria for IgG4-related Disease (ICPD). RESULTS: Of the 289 patients who underwent radical resection of primary liver cancer, 26 (9%) were diagnosed as benign, without histological evidence of malignancy, among them, 23 had sclerosing inflammation, 1 had cystadenoma, and 2 had xanthogranulomatous cholangitis. Additionally, 18 had a definitive diagnosis of IgG4-SC. The misdiagnosis rate was 19% (54/289), of which, 26 patients had benign disease, and 28 patients had malignancies. CONCLUSIONS: It is difficult to distinguish IgG-SC from PHC. The misdiagnosis has resulted in a large number of ineffective hepatectomies. Improving the detection rate of serum IgG4 (sIgG4) may therefore avoid misdiagnosis, surgery, and life-threatening complications.

Xanthogranulomatous cholecystitis: experience in 100 cases.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare presentation of chronic cholecystitis, characterized by xanthogranuloma, severe foam cells and fibrosis, and can be an inducement of difficulty in cholecystectomy. The purpose of this study was to review the clinical findings and imageology features of XGC and to optimize the treatment option. METHODS: This retrospective study collected clinical symptoms, demographics, imageology, operation records, histopathological findings, and postoperative complications of 100 patients with XGC after evaluating 50005 cholecystectomy specimens between 2009 and 2018 in a single institute. heir clinical symptoms, demographics, imageology, operation records, histopathological findings, and postoperative complications were collected and analyzed. RESULTS: Patients showed various clinical symptoms, ultrasonography was performed in all patients, CT and MRI were further arranged selectively before the operation, but none of the patients were prediagnosed. Fifty-two patients received open cholecystectomy. Laparoscopic cholecystectomy (LC) was planned in 48 patients within whom 8 cases were converted to open cholecystectomy. No partial cholecystectomy was performed. The intraoperative findings included cholecystolithiasis, choledocholithiasis, thickened gallbladder wall, lesions infiltrating into adjacent tissues, disordered Calot's triangle anatomy, enlarged regional lymph nodes, internal gallbladder fistula, and hepatic abscesses. Frozen-section analysis was performed in 48 patients under the suspicion of gallbladder carcinoma (GBCa), but only 2 cases were finally confirmed. CONCLUSIONS: The preoperative diagnosis of XGC was challenging. Open cholecystectomy was the most preferred treatment, and conversion to open was often necessary after LC.

Bioinformatic analysis of the expression and prognostic value of chromobox family proteins in human breast cancer.

Chromobox (CBX) family proteins control chromatin structure and gene expression. However, the functions of CBXs in cancer progression, especially breast cancer, are inadequately studied. We assessed the significance of eight CBX proteins in breast cancer. We performed immunohistochemistry and bioinformatic analysis of data from Oncomine, GEPIA Dataset, bcGenExMiner, Kaplan-Meier Plotter, and cBioPortal. We compared mRNA and protein expression levels of eight CBX proteins between breast tumor and normal tissue. The expression difference of CBX7 was the greatest, and CBX7 was downregulated in breast cancer tissues compared with normal breast tissues. The expression of CBX2 was strongly associated with tumor stage. We further analyzed the association between the eight CBX proteins and the following clinicopathological features: menopause age, estrogen receptor (ER), progesterone receptor (PR) and HER-2 receptor status, nodal status, P53 status, triple-negative status, and the Scarff-Bloom-Richardson grade (SBR) and Nottingham prognostic index (NPI). Survival analysis in the Kaplan-Meier Plotter database showed that the eight CBX proteins were significantly associated with prognosis. Moreover, CBX genes in breast cancer patients had a high net alteration frequency of 57%. There were significant co-expression correlations between the following CBX protein pairs: CBX4 positively with CBX8, CBX6 positively with CBX7, and CBX2 negatively with CBX7. We also analyzed the Gene Ontology enrichment of the CBX proteins, including biological processes, cellular components, and molecular functions. CBX 1/2/3/5/8 may be oncogenes for breast cancer, whereas CBX 6 and 7 may be tumor suppressors for breast cancer. All eight CBX proteins may be predictive for prognosis. Clinical trials are needed to confirm the significance of the eight CBX proteins in breast cancer.

Concurrent thymic carcinoma and middle lobe syndrome.

Surgery is one of the first-line treatments for thymic carcinoma. Middle lobe syndrome which is irresponsive to conservative therapies also calls for surgical intervention. We reported the case of a 65-year-old male who was diagnosed with coexistent thymic carcinoma and non-obstructive middle lobe syndrome. Before the operation, we took measures including repeated sputum examination, physical therapy, postural sputum drainage and bronchodilator inhalation. After removal of the mediastinal neoplasm, venous antibiotics were used to prevent pneumonia. The preexistent cough with purulent expectoration still lasted, but no pulmonary infection occurred. Our report indicates that middle lobe syndrome may not increase respiratory complications after midline sternotomy if it receives proper treatments before the operation. For patients with concurrent thymic carcinoma and persistent middle lobe atelectasis, the thymic tumor might be treated with priority to increase the chance of complete resection.

Phyllodes tumors of the breast in 2 sisters: Case report and review of literature.

RATIONALE: Phyllodes tumors (PT) of the breast are rare neoplasm originating from fibroepithelial component. To our knowledge, our report is the first reported case of PT in 2 sisters. PATIENT CONCERNS: We presented 2 cases of PT of the breast involving in 2 sisters. On physical examination of the younger sister, a firm mass measuring approximately 3 cm in diameter was identified in upper inner quadrant of the right breast. Physical examination of the elder sister revealed a 3 cm lump in upper outer quadrant of the left breast. DIAGNOSES: Histopathology of the younger sister revealed a malignant PT. The elder sister was diagnosed with borderline PT. INTERVENTIONS: The younger sister with malignant PT underwent right mastectomy. The elder sister with borderline PT was scheduled for wide resection of the mass in the left breast. OUTCOMES: After a follow-up of 23 months, no local or distant recurrence was observed. LESSONS: Our cases indicate that genetic factor may contribute to the risk of PT of the breast. Markers such as p53 and Ki-67 may have some correlation with PT malignancy.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling.

BACKGROUND: Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. METHODS: Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). RESULTS: Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). CONCLUSIONS: This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux.