Validation of the functional assessment of anorexia/cachexia therapy instrument to assess quality of life in maintenance hemodialysis patients with cachexia.

BACKGROUND: Many patients on maintenance hemodialysis (MHD) eventually suffer from cachexia. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its suitability for use in MHD patients has yet to be verified. This study aimed to explore the validation of the FAACT in MHD patients by conducting reliability and validity tests. METHODS: Qualified MHD patients were selected to complete the FAACT and Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaires, and their demographic data and biochemical test results were collected from electronic medical records. Next, the Cronbach's alpha coefficient, paired sample t test and ICC were used to analyze the scale consistency. Additionally, the association between the KDQOL-36 and FAACT was analyzed using Bland-Altman plots and Pearson correlation analysis. Finally, the patients were divided into groups to evaluate discriminant validity. RESULTS: A total of 299 patients were included in this study. The Cronbach's alpha coefficients of the FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their ICC exceeded 0.90. The correlation coefficients between the FAACT and its items ranged from 0.146 to 0.631, and the correlation coefficients between the FAACT and KDQOL-36 dimensions ranged from 0.446 to 0.617. The Bland-Altman plots between the FAACT and KDQOL-36 showed that only 3.3% of the points were outside the 95% limits of agreement. The effects of cachexia status (present or absent) on FAACT and ACS scores had effect sizes of 0.54 (P < 0.001) and 0.60 (P < 0.001), respectively. The FAACT and ACS also significantly discriminated between patients with and without inflammation (P < 0.001). CONCLUSIONS: The FAACT and ACS have acceptable reliability and validity in MHD patients and are suitable for measuring the quality of life of MHD patients with cachexia.

Recurrent granular cell tumor of the thyroid: a case report and literature review.

BACKGROUND: Granular cell tumor (GCT) of the thyroid is a rare benign tumor of Schwann cell origin with a favorable prognosis and only 10 cases have been reported so far in scientific literature. The present case study describes the first case of recurrent thyroid GCT. CASE PRESENTATION: Our case describes a 20-year-old woman who had undergone lobectomy for GCT of the thyroid 4 years ago. Hematoxylin-eosin (HE) staining revealed that the lesion was composed of epithelioid cells with an abundance of eosinophilic granular cytoplasm. Immunohistochemical analysis showed that tumor cells tested positive for S-100 protein and negative for desmin. Both histological and immunohistochemical analyses supported the diagnosis of recurrent GCT of the thyroid. CONCLUSIONS: Our case suggested that a tumor-free margin excision and post-operative follow-up are necessary for the treatment of GCT of the thyroid.

Multilevel regulation of RUVBL2 expression predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second-most lethal cancer worldwide with a complex pathogenesis. RuvB-like 2 (RUVBL2) was previously found to contribute to hepatocarcinogenesis. However, its expression, regulation and clinical significance have not been systematically evaluated in a large number of clinical samples. METHODS: Here, we performed a comprehensive analysis of RUVBL2 based on multiple datasets from 371 liver cancer patients of The Cancer Genome Atlas (TCGA) and on immunohistochemical staining in 153 subjects. In addition, the aberrant signaling pathways caused by RUVBL2 overexpression were investigated. RESULTS: We demonstrated that promoter hypomethylation, copy number gain, MYC amplification and CTNNB1 mutation were all responsible for RUVBL2 overexpression in HCC. High levels of RUVBL2 mRNA were associated with shorter recurrence-free survival time (RFS) but not overall survival time (OS). Furthermore, RUVBL2 protein was overexpressed in the nucleus and cytoplasm of HCC samples. Univariate and multivariate survival analyses showed that strong nuclear and cytoplasmic staining of RUVBL2 independently predicted worse OS and RFS with a 2.03-fold and a 1.71-fold increase in the hazard ratio, respectively. High levels of RUVBL2 promoted carcinogenesis through the heat shock protein 90 (HSP90)-Cell Division Cycle 37 (CDC37), AKT serine/threonine kinase (AKT) and mitogen-activated protein kinase (ERK/MAPK) pathways. CONCLUSION: The deregulation of RUVBL2 in HCC is influenced at the genomic, epigenetic and transcriptional levels. Our findings highlight the potential roles of RUVBL2 as a promising prognostic marker as well as a therapeutic target for HCC.

Clinicopathological features and surgical outcomes of four rare subtypes of primary liver carcinoma.

OBJECTIVE: This study aimed to analyze clinicopathological and prognostic features of four rare pathological subtypes of primary liver malignancies to make better understanding of their clinical features. METHODS: The clinicopathological data of 114 patients who were diagnosed with histologically proven four subtypes: clear cell carcinoma (CCC), giant cell carcinoma (GCC), sarcomatoid carcinoma (SC), and combined hepatocellular-cholangiocarcinoma (CHC) between October 1998 and August 2015 were reviewed. Their survival data were compared with those of 908 patients with histologically proven common hepatocellular carcinoma (HCC) (early- and advanced-stage HCC) during the same period. RESULTS: The outcome of the CCC group was better than that of the other three subgroups, and was similar to that of the early-stage HCC group. Also, the smallest tumor size and the highest incidence of pseudocapsule formation were observed in the CCC group. The SC group had the worst outcome among these four subgroups; the prognosis was much poorer than that of any other subgroups, even poorer than that of the advanced-stage common HCC group. No statistical difference was observed between the GCC, CHC and advanced-stage HCC groups on survival analysis. The incidences of tumor vascular emboli, TNM staging and non-radical resection were three risk factors of the prognosis. CONCLUSIONS: CCC is a low-degree malignancy and relatively favorably prognostic subtype of HCC. However, GCC, SC, and CHC are three rare high-degree malignancy subtypes of HCC with poor prognosis.

[Cavernous hemangioma of mediastinum: a report of 10 cases].

OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment and prognosis of cavernous hemangioma of mediastinum (CHM). METHODS: Retrospective analyses were performed for the clinical data of 10 CHM patients at our hospital along with a literature review. RESULTS: The clinical symptoms and signs were nonspecific. Although computed tomography (CT) showed mediastinal cystic mass, a definite diagnosis could not be reached. Complete surgical excision was performed with a pathological confirmation of CHM. Neither recurrence nor mortality occurred during the postoperative follow-up up to 12 years. CONCLUSIONS: CHM is rare and frequently misdiagnosed. Hypodensity or calcification inside mass on CT is diagnostic. A definite diagnosis is dependent upon typical tumor appearances and pathological report of puncture biopsy. Excision is an effective cure with a fair prognosis.

ABCC4 copy number variation is associated with susceptibility to esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cause of cancer-related death worldwide. However, previous genome-wide single nucleotide polymorphism association analyses have not explained the high heritability associated with ESCC. In this study, we performed genome-wide copy number variation (CNV) analysis on 128 discordant sibling pairs to identify novel genes that contribute to ESCC susceptibility. A total of 57 774 individual CNVs were identified, and an interactive network of common CNV-associated genes was constructed, which showed that several ABC transporter genes contain CNVs in ESCC patients. Independent validation of a CNV at 13q32.1 in 1048 northern Chinese Han subjects demonstrated that the amplification of ABCC4 significantly correlated with ESCC risk [odds ratio: 3.36 (1.65-7.93), P = 0.0013]. Immunohistochemistry staining suggested that high copy numbers correlated with increased protein levels. High expression of ABCC4 was an independent poor prognostic factor for ESCC [relative risk: 1.73 (1.10-2.73), P = 0.0181]. The CNV region showed strong enhancer activity. Furthermore, inhibition of ABCC4 protein in ESCC cells decreased cell proliferation and motility via the inhibition of COX-2, PGE2 receptors and c-Myc expression; AKT, extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation; and ß-catenin nuclear translocation in ESCC cells. In conclusion, the CNV at 13q32.1 is associated with ESCC susceptibility, and a gene within this locus, ABCC4, activates the oncogenic pathways in ESCC and thus facilitates cancer cell development and progression. A direct genetic contribution of ESCC risk through CNV common variants was determined in this study, and ABCC4 might therefore have predictive and therapeutic potential for ESCC.

Inhibition of atypical protein kinase Cι induces apoptosis through autophagic degradation of ß-catenin in esophageal cancer cells.

Atypical protein kinase Cι (PKCι) has been identified as an oncoprotein in esophageal squamous cell carcinomas. However, the mechanisms underlying the role of PKCι in this disease remain unclear. In the present work, we found that inhibition of PKCι expression by RNAi induced apoptosis via the down-regulation of ß-catenin in esophageal cancer cells. Furthermore, we found that PKCι regulated ß-catenin in an autophagy dependent way. Since down-regulation of ß-catenin induced by knockdown of PKCι could be rescued by autophagy inhibition; knockdown of PKCι activated autophagy and promoted the recruitment of ß-catenin into autophagosome. These results suggested that PKCι positively regulated ß-catenin through negatively regulated autophagy and depletion of PKCι promoted apoptosis via autophagic degradation of ß-catenin in esophageal cancer cells. These data provide new insights into PKCι signaling in human cancer.

[Detection and clinical implication of aneuploidy of chromosomes 11 and 20 in gastric adenocarcinoma].

OBJECTIVE: The aim of this study was to find out the value of chromosome aneuploidy in early diagnosis and prediction of postoperative recurrence of gastric adenocarcinoma (GAC). METHODS: Tissue samples, including 49 GAC, pairing pericancerous mucosa and normal gastric mucosa from the distant cutting margin were use in this study. Two centromere probes, Cen11 and Cen20 specific for chromosomes 11 and 20 were analyzed by FISH . The clinicopathological data were summarized. RESULTS: The incidence of aneuploidy of chromosome 11 in the tumors, pericancerous mucosa and normal gastric mucosa from the distant cutting margin were 83.7%, 40.8%, and 16.3%, respectively (P < 0.001), and those of chromosome 20 were 87.8%, 53.1%, and 16.3%, respectively (P < 0.001). The aneuploidy of Cen 11 displayed a significant correlation with Lauren's claasification, and lymph node metastasis (P < 0.05 for both). The pericancerous mucosa and normal gastric mucosa from the distant cutting margin displayed mainly chronic inflammatory changes, intestinal metaplasia and dysplasia. CONCLUSIONS: Aneuploidy of Cen11 and Cen20 in pericancerous mucosa may be used as a candidate marker for early diagnosis of gastric adenocarcinoma and may have a predictive value of postoperative recurrence.

[Correlation between BRAF V600E mutation and clinicopathologic features of papillary thyroid carcinoma].

OBJECTIVE: To study the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and its association with clinicopathologic features. METHODS: Two hundred and ninety-two patients with primary PTC encountered during the period from December 2010 to December 2012 and underwent surgery in Cancer Hospital, Chinese Academy of Medical Science were enrolled into the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF V600E mutation. Statistical analysis was performed with SPSS 16.0 for Windows. Association between BRAF mutation and clinicopathologic parameters was tested with the χ(2) test or Fisher exact test as appropriate. RESULTS: There were 87 males and 205 females in the cohort. The age of patients ranged from 13 to 84 years (mean = 43.1 years). BRAF V600E mutation was found in 190 cases (65.1%). The presence of BRAF V600E mutation correlated with age at diagnosis (older than 45 years), tumor volume (larger than 1 cm), extrathyroidal extension, classic type/tall-cell variant and advanced disease stage (P < 0.05). BRAF V600E mutation did not correlate significantly with gender, multicentricity, lymph node metastasis or anatomic location (P > 0.05). CONCLUSION: BRAF V600E mutation is associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF V600E mutation may be a potential prognostic factor in PTC patients.

Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy.

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

PD-L1 and B7-H3 are Effective Prognostic Factors and Potential Therapeutic Targets for High-Risk Thyroid Cancer.

The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2 cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2 cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer.

Clinicopathological features of incidentally detected metastatic thyroid papillary carcinoma in cervical lymph nodes of non-thyroid cancer patients: a retrospective analysis of 31cases.

BACKGROUND: The incidental finding of thyroid inclusions in lymph nodes of neck dissections of non-thyroid cancer patients is an unusual event. It is still controversial for pathologists about whether this represents benign inclusions or metastatic papillary thyroid carcinoma (PTC). This study is to analyze clinicopathological features of such cases in an attempt to explore their clinical implications. METHODS: Pathological data were searched for incidentally detected PTC of cervical lymph nodes in non-thyroid cancer cases. Clinicopathological characteristics were reevaluated and recorded. BRAF V600E protein expression and sequencing analysis was then performed in cases with sufficient tissues. RESULTS: 31 patients had an incidental finding of PTC in lymph nodes of patients with non-thyroid cancer. BRAF immunohistochemical staining were performed in 17 metastatic lymph nodes with sufficient tumor tissues, and 6 were positive. BRAF V600E point mutation was detected in 5 of 6 BRAF V600E positive cases. Subsequent imaging examinations of the thyroid showed no nodules or calcifications/benign nodules in 20 patients, and suspected malignant nodules in 5 patients. 12 patients underwent total thyroidectomy or ipsilateral lobectomy, and 6 showed PTC in postoperative pathological examinations. The remaining 19 patients without surgery were kept under active surveillance, and no one had recurrence of PTC. CONCLUSION: Incidentally discovered PTC in lymph nodes has usually interpreted as metastasis from a clinical occult thyroid primary cancer, but primary PTC was not always detected. This suggests it could be double occult lesions. With regards to concurrence with highly malignant tumor, most patients could keep regular surveillance.

MARCKSL1 interacted with F-actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia.

BACKGROUND: Emerging evidence indicates that myristoylated alanine-rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. METHODS: CCK8, Transwell and wound-healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. RESULTS: Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F-actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. CONCLUSION: MARCKSL1 promotes cell migration and invasion by interacting with F-actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas.

Background: This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs). Methods: In this prospective, single-arm, single-centre clinical trial, patients meeting the inclusion criteria were treated with preoperative neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 175 mg/m2 paclitaxel. This was followed by surgery and postoperative adjuvant therapy. The primary endpoint was the postoperative pathological complete response (pCR) rate. All statistical analyses were performed using SPSS 26. Results: A total of 22 patients were enrolled. The location of primary lesion showed: hypopharynx were 15 (68.2%), oropharynx were 6 (27.3%) and oral cavity was 1 (4.5%). The postoperative pCR rate, was 36.4% (8/22), and there was no delay to surgery due to adverse drug reactions. The rate of laryngeal function preservation was 90.9% (20/22). Delayed wound healing was the main surgical complication, with an incidence of 22.7% (5/22). The median follow-up time was 9.5 months, and only 1 patient (4.55%) suffered a regional recurrence. Conclusion: Preoperative treatment with pembrolizumab and chemotherapy in resectable LA-HNSCC has a high pCR rate with no significant impact on surgical safety. This treatment was found to increase the rate of laryngeal function preservation. However, the effects of neoadjuvant immunotherapy on long-term prognosis in LA-HNSCCs require further study.

Clinicopathological practice in the differential diagnosis of mucoepidermoid carcinoma from neoplasms with mucinous component.

Background: The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution. Methods: Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs. Results: There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs (p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement. Conclusion: The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

PD-L1 expression in recurrent or metastatic head and neck squamous cell carcinoma in China (EXCEED study): a multicentre retrospective study.

AIMS: Programmed death-ligand 1 (PD-L1) is known to be highly expressed in various malignancies, including head and neck squamous cell carcinoma (HNSCC). We aimed to determine the prevalence of PD-L1 expression in recurrent or metastatic HNSCC (R/M HNSCC) among Chinese patients. METHODS: This multicentre, retrospective analysis of data from six centres in China included patients with R/M HNSCC treated from 9 August 2021 to 28 February 2022. PD-L1 expression in tumour tissue was assessed and represented using a combined positive score (CPS). The χ2 and Cochran-Mantel-Haenszel χ2 tests were used to compare the prevalence of different PD-L1 expression statuses according to related co-variables. RESULTS: For all 402 examined patients with R/M HNSCC, 168 cases (41.8%) had PD-L1 expression with a CPS ≥20, and 337 cases (83.8%) had PD-L1 expression with a CPS ≥1. Between the PD-L1 CPS ≥20 group and PD-L1 CPS <20 group, statistically significant differences were observed for variables of sex (p<0.001), smoking habit (p=0.0138 for non-smokers vs current smokers) and primary tumour site (p<0.001 for hypopharynx vs oral cavity and p=0.0304 for larynx vs oral cavity, respectively). CONCLUSION: PD-L1 with CPS ≥20 was expressed in about 41.8% of cases with R/M HNSCC among Chinese patients, and PD-L1 expression was significantly associated with sex, smoking history and primary tumour site. Our findings regarding the variables related to PD-L1 expression level provide insight for clinical practice and a solid basis for future research on immunotherapy in HNSCC. TRIAL REGISTRATION NUMBER: ISRCTN10570964.

[Analysis of clinicopathological features of intestinal neuroendocrine neoplasms].

OBJECTIVE: To analyze the clinicopathological features of intestinal neuroendocrine neoplasms. METHODS: The clinicopathological features of 114 patients with intestinal neuroendocrine neoplasms treated in our hospital from April 1999 to March 2011 were retrospectively reviewed, including tumor location, histological classification, muscle invasion, metastasis and clinical data. Immunohistochemical SP staining was applied to examine the expression of 15 markers in the tumor specimens. RESULTS: The male:female ratio of the patients was 1.33, and most of the tumors were located in the rectum of polypoid type. The positive rate of immunohistochemical staining of Syn expression was 97.4%, NSE 95.6%, PGP9.5 84.2%, CD56 75.4%, CD57 72.8%, CgA 43.0%, S100 36.0%, Syn combined with CgA 99.1%, and the two marker Syn and CgA combined with any one of CD56, CD57 or PGP9.5 reached to 100%. The 5-years survival rates of G1, G2 were 98.9% and 76.9%, respectively, and the overall 5-year survival rate of intestinal neuroendocrine neoplasms was 92.9%. Two of the 7 cases of poor differentiated neuroendocrine carcinoma died after operation, another 2 of them lost to follow up. Others were still alive during the follow-up. Among the 3 patients with small cell carcinoma, two survived for 8 to 24 months after operation, and one lost to follow up. Two cases of mixed adenoneuroendocrine carcinoma (MANEC) were still surviving during the follow-up. Different histological types of intestinal neuroendocrine neoplasms were significantly different in sex, primary tumor site, pathological type, tumor size, types of combined tumors, pT stage, aggressive nervous and vascular invasion, and metastasis (all P < 0.05). Single factor analysis of the intestinal neuroendocrine neoplasms indicated that tumor size (Z = -6.334, P < 0.001), histological classification (χ(2) = 31.175, P < 0.001) and muscle invasion (χ(2) = 63.567, P < 0.001) were associated with metastasis of intestinal neuroendocrine neoplasms. Logistic analysis showed that muscle invasion was the main behavior risk factor of this tumor (OR = 1.827, P < 0.05). CONCLUSIONS: Intestinal neuroendocrine neoplasms usually occur in males, and the most common involved organ is the rectum. Their histological types are related to the prognosis, and the depth of invasion is an important metastasis factor of intestinal neuroendocrine neoplasms. Of the neuroendocrine makers, the combination of CgA and Syn shows a higher diagnostic sensitivity.

The first successful treatment and genetic sequencing of primary hepatic adenosarcoma with sarcomatous overgrowth: a case report.

Adenosarcoma is a rare type of tumor with a mixture of epithelial and stromal components and often occurs in the female reproductive system. Primary hepatic adenosarcoma (PHAS) is extremely rare, with only two cases reported so far. Both patients had poor outcomes. Here, we report the case of a 36-year-old man with pain under the xiphoid process who was diagnosed with a bile duct tumor. He was treated with adjuvant radiotherapy when surgery was performed on him. Pathologically, the tumor contained benign epithelial tissue, and the submucosa of the bile duct in the liver showed infiltrating growth of spindle cell components. The cells were dense, mildly heterotypic, and occasionally mitotic, and the patient was diagnosed with PHAS. Whole-exome sequencing results showed that a total of 12 mutations were shared by the two tissues. The patient received adjuvant radiotherapy and he was tumor-free until 31 months postoperatively. This case will provide some references of the disease to other researchers.

A case report of primary colonic paraganglioma with lymph node metastasis.

Background: Paraganglioma is a kind of neuroendocrine tumor that originates from paraganglia outside the adrenal gland. Gastrointestinal tract paraganglioma is very rare and only four cases of paraganglioma originating in the colon have been reported. Case Presentation: We report a case of metastatic paraganglioma originating in the colon, in which the differential diagnosis was established by comprehensively considering clinical information, histology, immunohistochemistry, and findings of fluorescence in situ hybridization and next generation sequencing analyses. The patient has remained well for over 14 months after the treatment. Conclusion: Since all paraganglioma have metastatic potential, we believe that radical surgical resection and regular follow-up are necessary. Genetic testing may be indicative of metastatic potential and prognosis. Because colonic paraganglioma is very rare, differential diagnosis is very important. Our report provides experience for the diagnosis and study of paraganglioma in rare sites.