Predicting the Recurrence of Gastric Cancer Using the Textural Features of Perigastric Adipose Tissue on [18F]FDG PET/CT.

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.

Prognostic significance of liver CT-attenuation and 18F-FDG uptake for predicting hepatic recurrence following curative resection of colorectal cancer.

OBJECTIVE: This study investigated the predictive values of computed tomography (CT)-attenuation and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in the liver for the hepatic recurrence of colorectal cancer. SUBJECT AND METHODS: This study retrospectively included 257 colorectal cancer patients who underwent staging 18F-FDG positron emission tomography (PET)/CT and were subsequently treated with curative surgical resection. Using non contrast-enhanced CT images in PET/CT, the liver-spleen ratio and liver-spleen difference of CT-attenuation and CT-attenuation of the liver were calculated. The maximum and mean 18F-FDG uptake in the liver was measured using the PET images. The relationship of these five liver parameters to recurrence-free survival (RFS), hepatic RFS, and extrahepatic RFS was assessed. RESULTS: In univariate survival analysis, the liver-spleen ratio, liver-spleen difference, and maximum 18F-FDG uptake of the liver were significant predictors of both RFS and hepatic RFS (P<0.05), whereas none of the five liver parameters were significantly associated with extrahepatic RFS (P>0.05). Patients with a low liver-spleen ratio and liver-spleen difference and a high maximum 18F-FDG uptake showed better hepatic RFS than those with a high liver-spleen ratio and liver-spleen difference and a low maximum 18F-FDG uptake. In multivariate analysis, the liver-spleen ratio, liver-spleen difference, and maximum 18F-FDG uptake of liver remained significant predictors for hepatic RFS after adjusting for age, sex, obesity, andstage (P<0.05). CONCLUSION: Computed tomography-attenuation and maximum 18F-FDG uptake in the liver on 18F-FDG PET/CT were significant predictive factors for hepatic RFS in patients with colorectal cancer after curative resection.

Pd-Catalyzed asymmetric [5 + 2] cycloaddition of vinylethylene carbonates and cyclic imines: access to N-fused 1,3-oxazepines.

A Pd-catalyzed asymmetric [5 + 2] cycloaddition reaction was developed for the synthesis of N-fused 1,3-oxazepines using vinylethylene carbonates and sulfamate-derived cyclic imines. Under mild reaction conditions, a series of optically active N-fused 1,3-oxazepines were synthesized in good yields (up to 89%) and enantioselectivities (up to 90 : 10 er), indicating this method as a straightforward approach to enantiomerically enriched 1,3-oxazepine derivatives. The synthetic utility of the presented reaction was further demonstrated by the successful transformation of the resulting 1,3-oxazepines to useful polycyclic N-fused 1,3-oxazepanes.

Low LATS2 expression is associated with poor prognosis in non-small cell lung carcinoma.

Large tumor suppressor kinase 2 (LATS2) is a core component in the Hippo signaling pathway, and it functions as a tumor suppressor associated with tumor cell proliferation and apoptosis. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC). We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens using tissue microarrays. Low LATS2 expression was significantly related to disease recurrence (p = 0.047). In survival analysis, the low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than the high expression group. In multivariate analysis, downregulated LATS2 expression in NSCLC could be an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major NSCLC subtypes, squamous cell carcinoma and adenocarcinoma. The low LATS2 expression group showed worse prognosis than the high LATS2 expression group (OS [p = 0.144] and DFS [p = 0.022] in squamous cell carcinoma and OS [p = 0.045] and DFS [p = 0.271] in adenocarcinoma). We demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma.

Clinicopathologic implications of TNFAIP3/A20 deletions in extranodal NK/T-cell lymphoma.

The A20/Tumor necrosis factor-alpha-induced protein 3 (A20/TNFAIP3) is a negative regulator of NF-κB signaling. We analyzed the clinicopathologic implications of A20 deletions in extranodal NK/T-cell lymphoma (NKTL). Fluorescence in situ hybridization analysis of the A20 gene was performed using archived formalin-fixed tissues in 49 cases of NKTL. Among the 49 NKTL patients (median age, 48 y [10-79]), stage I-II (75% [36/48]) and upper aerodigestive tract (UAT)-origin (84% [41/49]) were predominant. All A20 deletions were monoallelic and found in cases with UAT-origin, accounting for 18% (9/49) of all NKTLs and 22% (9/41) of UAT-origin. In univariate analysis, overall survival (OS) and progression-free survival (PFS) were associated with stage, international prognostic index (IPI), B symptoms and number of extranodal sites, and OS with performance status and non-UAT-origin, but none with A20 deletion. In multivariate analysis, IPI predicted OS (P = .008 [HR = 23.4]) and PFS (P = .005 [HR = 34.0]). Risk was divided by B symptoms (P = .001 [OS]; P = .034 [PFS]) in low IPI subset (n = 36), and by A20 deletion (P = .029 [PFS]) in high IPI subset (n = 13). These results suggest a clinicopathologic implication of A20 in progression of NKTL.

Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma.

BACKGROUND: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. METHODS: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10% of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. RESULTS: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6%) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5%) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P <  0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. CONCLUSIONS: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.

Increased expression of forkhead box M1 is associated with aggressive phenotype and poor prognosis in estrogen receptor-positive breast cancer.

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.

Adipose Tissue Quantification Improves the Prognostic Value of GLIM Criteria in Advanced Gastric Cancer Patients.

The present study investigated whether the risk of recurrence after curative surgery could be further stratified by combining the Global Leadership Initiative on Malnutrition (GLIM) criteria and changes in subcutaneous (SAT) and visceral (VAT) adipose tissue mass after surgery in patients with advanced gastric cancer (AGC). This study retrospectively analyzed 302 patients with AGC who underwent curative surgery. Based on the GLIM criteria, patients were classified into malnourished and non-malnourished groups. The cross-sectional areas of SAT and VAT were measured from preoperative and 6-month post-operative computed tomography (CT) images. Multivariate survival analyses demonstrated that GLIM-defined malnutrition (p = 0.008) and loss of VAT after surgery (p = 0.008) were independent risk factors for recurrence-free survival (RFS). Evaluation of the prognostic value of combining the two independent predictors showed that malnourished patients with a marked loss of VAT had the worst 5-year RFS rate of 35.2% (p < 0.001). Preoperative GLIM-defined malnutrition and a loss of VAT during the first 6 months after surgery were independent predictors for RFS in patients with AGC. Changes in the VAT area after surgery could further enhance the prognostic value of the GLIM criteria for predicting the risk of gastric cancer recurrence.

Relationship of FDG PET/CT imaging features with tumor immune microenvironment and prognosis in colorectal cancer: a retrospective study.

BACKGROUND: Imaging features of colorectal cancers on 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) have been considered to be affected by tumor characteristics and tumor immune microenvironment. However, the relationship between PET/CT imaging features and immune reactions in tumor tissue has not yet been fully evaluated. This study investigated the association of FDG PET/CT imaging features in the tumor, bone marrow, and spleen with immunohistochemical results of cancer tissue and recurrence-free survival (RFS) in patients with colorectal cancer. METHODS: A total of 119 patients with colorectal cancer who underwent FDG PET/CT for staging work-up and received curative surgical resection were retrospectively enrolled. From PET/CT images, 10 first-order imaging features of primary tumors, including intensity of FDG uptake, volumetric metabolic parameters, and metabolic heterogeneity parameters, as well as FDG uptake in the bone marrow and spleen were measured. The degrees of CD4+, CD8+, and CD163 + cell infiltration and interleukin-6 (IL-6) and matrix metalloproteinase-11 (MMP-11) expression were graded through immunohistochemical analysis of surgical specimens. The relationship between FDG PET/CT imaging features and immunohistochemical results was assessed, and prognostic significance of PET/CT imaging features in predicting RFS was evaluated. RESULTS: Correlation analysis with immunohistochemistry findings showed that the degrees of CD4 + and CD163 + cell infiltration and IL-6 and MMP-11 expression were correlated with cancer imaging features on PET/CT. Patients with enhanced inflammatory response in cancer tissue demonstrated increased FDG uptake, volumetric metabolic parameters, and metabolic heterogeneity. FDG uptake in the bone marrow and spleen was positively correlated with the degree of CD163 + cell infiltration and IL-6 expression, respectively. In multivariate survival analysis, the coefficient of variation of FDG uptake in the tumor (p = 0.019; hazard ratio, 0.484 for 0.10 increase) and spleen-to-liver uptake ratio (p = 0.020; hazard ratio, 24.901 for 1.0 increase) were significant independent predictors of RFS. CONCLUSIONS: The metabolic heterogeneity of tumors and FDG uptake in the spleen were correlated with tumor immune microenvironment and showed prognostic significance in predicting RFS in patients with colorectal cancer.

Relationship of FDG Uptake of the Reticuloendothelial System with Tumor Immune Microenvironment and Prognosis in Patients with Gastric Cancer.

2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of the reticuloendothelial system, including the bone marrow (BM) and spleen, on positron emission tomography/computed tomography (PET/CT) has been shown to be a significant prognostic factor in diverse malignancies. However, the relationship between FDG uptake of the BM and spleen and histopathological findings, including the tumor immune microenvironment, has not been fully evaluated. This study aimed to investigate the relationship of FDG uptake in the BM and spleen with histopathological findings and recurrence-free survival (RFS) in patients with gastric cancer. Seventy patients with gastric cancer who underwent pre-operative FDG PET/CT and subsequent curative surgery were retrospectively enrolled. On image analysis, the BM-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) were measured from PET/CT images, and on immunohistochemical analysis, the densities of immune cell infiltration in the tumor tissue were graded. The BLR and SLR showed significant positive correlations with the grades of CD163 cell and CD8 cell infiltration in the tumor tissue, respectively (p < 0.05). In multivariate survival analysis, both BLR and SLR were significant predictors of RFS (p < 0.05). FDG uptake in the BM and spleen might be potential imaging biomarkers for evaluating tumor immune microenvironment conditions and predicting RFS in patients with gastric cancer.

Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelial-mesenchymal transition expression in patients with hepatocellular carcinoma.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269-0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019-2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT- showed a significantly better prognosis than those who were TIL-/EMT+ (P = 0.049). Conclusion: This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti-PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

Relationship of FDG PET/CT Textural Features with the Tumor Microenvironment and Recurrence Risks in Patients with Advanced Gastric Cancers.

The relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) textural features and histopathological findings in gastric cancer has not been fully evaluated. We investigated the relationship between the textural features of primary tumors on FDG PET/CT with histopathological findings and recurrence-free survival (RFS) in patients with advanced gastric cancer (AGC). Fifty-six patients with AGC who underwent FDG PET/CT for staging work-ups were retrospectively enrolled. Conventional parameters and the first- and second-order textural features of AGC were extracted using PET textural analysis. Upon histopathological analysis, along with histopathological classification and staging, the degree of CD4, CD8, and CD163 cell infiltrations and expressions of interleukin-6 and matrix-metalloproteinase-11 (MMP-11) in the primary tumor were assessed. The histopathological classification, Lauren classification, lymph node metastasis, CD8 T lymphocyte and CD163 macrophage infiltrations, and MMP-11 expression were significantly associated with the textural features of AGC. The multivariate survival analysis showed that increased FDG uptake and intra-tumoral metabolic heterogeneity were significantly associated with an increased risk of recurrence after curative surgery. Textural features of AGC on FDG PET/CT showed significant correlations with the inflammatory response in the tumor microenvironment and histopathological features of AGC, and they showed significant prognostic values for predicting RFS.

Scalp metastasis of advanced gastric cancer.

Head and neck cutaneous metastasis of advanced gastric cancer is uncommon, and scalp metastasis is particularly rare. We present the case of a 60-year-old man who was diagnosed with cutaneous metastasis on the scalp originating from advanced gastric cancer. The patient was referred to the plastic surgery department for a scalp mass near the hairline. He had been diagnosed with advanced gastric cancer and undergone total gastrectomy and Roux esophagojejunostomy 3 years previously. The differential diagnosis for a single flesh-colored nodule on the scalp included benign tumors such as epidermal cyst or lipoma; therefore, the patient underwent excision and biopsy. In the operative field, the mass was found to be located in the frontalis muscle. The biopsy result showed that the mass was a metastatic lesion of advanced gastric cancer. Whole-body computed tomography revealed a gastric tumor with blood vessel infiltration, peritoneal carcinomatosis, liver metastasis, and multiple disseminated subcutaneous metastases. Although scalp metastasis originating from an internal organ is extremely rare, plastic surgeons should always consider a metastatic lesion in the differential diagnosis if a patient with a scalp lesion has a history of malignant cancer.

Penile schwannoma mistaken for hemangioma: a rare case report and literature review.

Penile neoplasm is uncommon. Schwannomas of the penis are especially rare. For this reason, it is difficult to get an accurate impression to enable decision making. This report primarily deals with the mistaken diagnosis of hemangioma, to the surgery, and the follow-up in real-world. A 38-year-old male patient presented with a palpable mass in the penile root that increased in size with erection. One year after the mass had been found, the patient visited the hospital and complained that the mass was growing. Moreover, the patient explained that the mass seemed to increase during penile erection. On physical examinations, a 2 cm mass without tenderness was palpated in the left penoscrotal junction. About 2.1 cm in size, an isoechoic mass was observed next to the corpus cavernosum on ultrasonography. There was high vascularity inside of the mass. Excision and biopsy were decided upon. Following surgery, a schwannoma was confirmed by pathology. After three months, the patient did not complain of any symptoms and had normal erectile function. Most of these tumors are benign. By December 2020, 40 cases were reported, of which 6 were diagnosed as malignant. The most frequent occurrence site is the penile shaft. In all cases, surgical resection was performed and no recurrence was found. The aim of this case report is to assist clinicians in choosing the best treatment option when faced with this rare condition by discussing the radiological, pathological, and clinical course.

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT.

The purpose of this study was to evaluate the prognostic significance of FDG uptake of bone marrow (BM SUV) and to investigate its role combined with radiomic features of primary tumors in improving the prediction of overall survival (OS) in patients with pancreatic cancer. We retrospectively enrolled 65 pancreatic cancer patients with staging FDG PET/CT. BM SUV and conventional imaging parameters of primary tumors including total lesion glycolysis (TLG) were measured. First-order and higher-order textural features of primary cancer were extracted using PET textural analysis. Associations of PET/CT parameters of bone marrow (BM) and primary cancer with OS were assessed. BM SUV as well as TLG and first-order entropy of pancreatic cancer were significant independent predictors of OS in multivariable analysis. A PET/CT scoring system based on the cumulative scores of these three independent predictors enabled patient stratification into three distinct prognostic groups. The scoring system yielded a good prognostic stratification based on subgroup analysis irrespective of tumor stage and treatment modality. BM SUV was an independent predictor of OS in pancreatic cancer patients. The PET/CT scoring system that integrated PET/CT parameters of primary tumors and BM can provide prognostic information in pancreatic cancer independent of tumor stage and treatment.

Isolated temporalis muscle metastasis of renal cell carcinoma.

Isolated head and neck metastasis of renal cell carcinoma (RCC) is relatively rare and metastasis to the temple area is very rare. Here, we present the case of a 51-year-old man who was diagnosed with RCC 2 years earlier and had a contralateral metastatic temple area lesion. The patient who was diagnosed with renal cell cancer and underwent a nephrectomy 2 years ago was referred to the plastic surgery department for a temple mass on the contralateral side. In the operative field, the mass was located in the temporalis muscle with a red-to-purple protruding shape. Biopsy of the mass revealed a metastatic RCC lesion. Computed tomography imaging showed a lobulated, contoured enhancing lesion. Positron emission tomography/computed tomography imaging showed high-fluorodeoxyglucose uptake in the right temporalis muscle. The patient underwent wide excision of the metastatic RCC including the temporalis muscle at the plastic surgery department. Skeletal muscle metastasis of head and neck lesions is extremely rare in RCC. Isolated contralateral temporalis muscle metastasis in RCC has not been previously reported in the literature. If a patient has a history of malignant cancer, plastic surgeons should always consider metastatic lesions of head and neck tumors. Because of its high metastatic ability and poor prognosis, it is very important to keep this case in mind.

Prognostic significance of imaging features of peritumoral adipose tissue in FDG PET/CT of patients with colorectal cancer.

PURPOSE: This study investigated the relationship of imaging features of primary tumor and peritumoral VAT on PET/CT with histopathological findings of peritumoral VAT and recurrence-free survival (RFS) in patients with colorectal cancer. METHODS: We retrospectively reviewed 133 patients diagnosed with colorectal cancer who underwent staging FDG PET/CT and received curative surgery. Histogram-based imaging features of primary tumor and peritumoral VAT were extracted from PET/CT images. Based on histopathological analysis of peritumoral VAT, the degree of CD4, CD8, and CD163 cell infiltration and the expression of matrix metalloproteinase-11 and interleukin 6 (IL-6) were graded. Differences in imaging parameters based on the histopathological results and the relationships between imaging features and RFS were assessed. RESULTS: Mean CT-attenuation and SUV of peritumoral VAT showed significant positive correlation with CD163 cell infiltration and IL-6 expression of peritumoral VAT. Univariable survival analysis revealed significant correlation between RFS and the mean CT-attenuation, mean SUV, and first-order SUV entropy of peritumoral VAT (p < 0.05). Multivariable analysis indicated that mean SUV and SUV entropy of peritumoral VAT remained significant predictors of RFS after adjustment for age, sex, and T stage (p < 0.05). CONCLUSION: FDG uptake of peritumoral VAT was significantly associated with inflammatory response in peritumoral VAT and was an independent predictor of RFS in colorectal cancer patients.

Reconstruction of a Neglected, Extensor Hallucis Longus Tendon Rupture Using Interposed Scar Tissue: A Case Report and Literature Review.

Injury of the extensor hallucis longus (EHL) tendon is relatively rare, but surgical repair is necessary to prevent deformity and gait disturbance. Primary suturing is possible if the condition is acute, but not when it is chronic. The scar tissue between the ruptured ends is a proliferative tissue composed of fibroblasts and collagen fibers. Given the histological similarity to normal tendons, several studies have reported tendon reconstruction using scar tissue. Here, we report a reconstruction of a neglected EHL rupture using interposed scar tissue. A 54-year-old female visited our clinic with a weak extension of a big toe. She had dropped a knife on her foot a month prior, but did not go to hospital. The wound had healed, but she noted dysfunctional extension of the toe and increasing pain. Magnetic resonance imaging (MRI) revealed that EHL continuity was lost and that the proximal tendon stump was displaced toward the midfoot. Scar tissue running in the direction of the original ligament was observed between the ruptured ends. In the surgical field, the scar tissue formed a shape similar to the extensor tendon. Therefore, we performed tendon reconstruction using the interposed scar tissue. For the first 2 postoperative weeks, the ankle and foot were immobilized to protect the repair. Six weeks after surgery, the patient commenced full weight-bearing. At the 3-month follow-up, active extension of the hallux was possible, with a full range of motion. The patient did not feel any discomfort during daily life. Postoperative MRI performed at 1 year revealed that the reconstructed EHL exhibited homogeneously low signal intensity, and was continuous. The AOFAS Hallux Metatarsophalangeal-Interphalangeal scale improved from 57 to 90 points and the FAAM scores improved from 74% to 95% (the Activities of Daily Living subscale) and from 64% to 94% (the Sports subscale). Scar tissue reconstruction is as effective as tendon autografting or allografting, eliminates the risk of donor site morbidity and infection, and requires only a small incision and a short operative time.

Loss of ARID1A expression is associated with poor prognosis in non-small cell lung cancer.

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC.

Clinicopathological correlation of PD-L1 and TET1 expression with tumor-infiltrating lymphocytes in non-small cell lung cancer.

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.