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Immunotherapy shows prospects in treating advanced medullary thyroid carcinoma although controversial reports are present. Recently, histological grading has been applied to medullary thyroid carcinoma by the Ki-67 index, mitotic figures, and tumor necrosis. However, the interrelation of PD-L1 expression, the Ki-67 index, and major genetic alterations of sporadic medullary thyroid carcinoma has not been fully reported. We examined the expression of PD-L1 (SP142 and 22C3) and the Ki-67 index immunohistologically and detected the major genetic alterations by next-generation sequencing in a cohort of sporadic medullary thyroid carcinomas, studied their survival impact, and discussed their interrelation. We identified that a high Ki-67 index ( 2%) and positive RET M918T mutation were correlated with poor disease-free survival but were not correlated with PD-L1 expression. All PD-L1 positive tumors were RET M918T mutation negative, and PD-L1 expression was positively correlated with HRAS mutation. The Ki-67 index was correlated with neither PD-L1 expression nor major genetic alterations. Our results indicate that immunotherapy targeting PD-L1/PD-1 might be more effective for patients with sporadic medullary thyroid carcinoma harboring HRAS mutations.

Anaplastic thyroid carcinoma (ATC) is a highly malignant tumor with invasive nature. Most patients present with locally advanced and/or distant metastatic diseases that are difficult to treat. We report a case of a previously inoperable patient with v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutated ATC. After a trial of neoadjuvant Dabrafenib/Trametinib with immunotherapy, the tumor became operable, and surgical pathology indicated a pathologic complete response (pCR). We also reviewed cases from the literature that utilized neoadjuvant BRAF-directed therapy in ATCs. These cases emphasize that BRAF-and immune-directed therapy is a feasible option in patients with inoperable ATC and may lead to improved outcomes.

ALK-positive histiocytosis (APH) is a newly defined entity with specific histological features and a highly recurrent KIF5B-ALK gene fusion. APH is characterized by clonal proliferation of histiocytes and can present as either systemic or localized. It was first described in infants and then expanded to older children and adults. Although lung involvement has been shown in three systemic cases, localized lung lesions have not previously been reported. The ALK gene has many fusion partners in addition to KIF5B in APH. Here, we report a striking case of localized APH in the lung harboring a rare EML4-ALK rearrangement in a 52-year-old Chinese woman. Furthermore, we reviewed the previously published APH cases, analyzed the partner genes of the ALK fusions, and explored the role of patient ethnicity. We discovered a link between ethnicity and this rare disease.

Current histopathological diagnosis methods cannot distinguish the two types of thyroid carcinoma: clinically significant carcinomas with a potential risk of recurrence, metastasis, and cancer death, and clinically insignificant carcinomas with a slow growth rate. Both thyroid tumors are diagnosed as "carcinoma" in current pathology practice. The clinician usually recommends surgery to the patient and the patient often accepts it because of cancer terminology. The treatment for these clinically insignificant carcinomas does not benefit the patient and negatively impacts society. The author proposed risk stratification of thyroid tumors using the growth rate (Ki-67 labeling index), which accurately differentiates four prognostically relevant risk groups based on the Ki-67 labeling index, ≥30%, ≥10 and30%,5 and10%, and ≤5%. Indolent thyroid tumors with an excellent prognosis have the following four features: young age, early-stage (T1-2 M0), curatively treated, and low proliferation index (Ki-67 labeling index of ≤5%), and are unlikely to recur, metastasize, or cause cancer death. Accurate identification of these indolent tumors helps clinicians select more conservative treatments to avoid unnecessary aggressive (total thyroidectomy followed by radio-active iodine) treatments. Clinicians can alleviate the fears of patients by confirming these four features, including the low proliferation rate, in a pathology report immediately after surgery when patients are most concerned.

BACKGROUND: Distinguishing aggressive pT1 papillary thyroid carcinomas (PTCs) from indolent PTCs before or during surgery is important. To the best of our knowledge, few reports in the literature have examined the value of the cytomorphologic features of PTC as predictors of aggressiveness. METHODS: This retrospective study included 226 pT1 PTC patients who underwent preoperative fine-needle aspiration cytology (FNAC) and surgery at Peking University Cancer Hospital between January 2018 and December 2019. Data on the clinical characteristics and pathological results were obtained from the electronic medical record database. All FNAC smears were blindly reviewed by two independent cytopathologists, and the associations between nine cytomorphologic features (lymphocytes, multinucleated giant cells, cellularity, cellular adhesiveness, nuclear size, nuclear pleomorphism, nuclear membrane regularity, intranuclear pseudoinclusions and the amount of cytoplasm) and clinicopathological parameters were statistically analyzed. RESULTS: Univariate analysis showed that cellularity, intranuclear pseudoinclusions, cellular adhesiveness, nuclear size, and nuclear pleomorphism were strong predictors of some clinicopathological parameters such as extracapsular invasion (ECI) and lymph node metastasis (LNM). Multivariate analysis confirmed that cellular adhesiveness was a strong independent predictor of ECI (P=0.001) and LNM (P

BACKGROUND: Aquaporin2 (AQP2) is water channel protein that is widely distributed among mammalian tissues and plays a major role in water homeostasis. However, little is known about the expression and significance of AQP2 in human adrenal tumors. Thus, we performed an immunohistochemical investigation of AQP2 in normal and neoplastic adrenal tissues. METHODS: AQP2 protein expression was investigated in 190 adrenal tumor patients using immunohistochemistry. Correlation between protein expression and clinicopathological features was statistically analyzed. RESULTS: We demonstrated immunopositivity for AQP2 in all adrenal medulla-originating tumors, including 96 pheochromocytomas (PCC), 7 metastatic pheochromocytomas (MPCC), and 10 neuroblastic tumors (NT) and 13 extra-adrenal paragangliomas (EAPGL). Whereas, APQ2 was absent from the 52 adrenal cortical adenomas and 2 adrenal cortical carcinomas examined. The 10 metastatic carcinomas examined in adrenal tissue were also negative for AQP2. In 82 (85%) of the 96 samples from patients with PCC, we studied the relationship between clinicopathologic factors and AQP2 expression and our findings suggested that the tumors that exhibited diffuse expression pattern of AQP2 were larger in diameter than those exhibiting focal (P=0.007) or mediate expression pattern (P=0.001). CONCLUSIONS: AQP2 protein is significantly expressed in normal adrenal medullary tissues and medullary tumors (including PCC, MPCC and NT) as well as EAPGL. AQP2 expression may indicate the origin of normal adrenal tissues, and its expression in cancer tissue may reflect the maintenance of water metabolism via AQP2 during tumorigenesis. AQP2 may serve as a valuable marker for the differential diagnosis of adrenal tumors.

Accurate detection of HER2 expression through immunohistochemistry (IHC) is of great clinical significance in the treatment of breast cancer. However, manual interpretation of HER2 is challenging, due to the interobserver variability among pathologists. We sought to explore a deep learning method to predict HER2 expression level and gene status based on a Whole Slide Image (WSI) of the HER2 IHC section. When applied to 228 invasive breast carcinoma of no special type (IBC-NST) DAB-stained slides, our GrayMap+ convolutional neural network (CNN) model accurately classified HER2 IHC level with mean accuracy 0.952 ± 0.029 and predicted HER2 FISH status with mean accuracy 0.921 ± 0.029. Our result also demonstrated strong consistency in HER2 expression score between our system and experienced pathologists (intraclass correlation coefficient (ICC) = 0.903, Cohen’s κ = 0.875). The discordant cases were found to be largely caused by high intra-tumor staining heterogeneity in the HER2 IHC group and low copy number in the HER2 FISH group.

Prostate artery embolization is a well-known and promising treatment for benign prostatic hyperplasia, with the quantum leaps of research in medicine. We aim to provide an up-to-date review of the novel technique, including large retrospective studies and randomized control trials, ends with discussions of advantages and disadvantages of this minimally invasive technique.

BACKGROUND Hepatocellular carcinoma (HCC) is a common cancer and a leading cause of tumor-related death. Patients with large HCC (≥ 8 cm) are at an advanced stage and have poor prognosis, and hepatic resection may not be suitable, and the incidence of postoperative recurrence is high. AIM To evaluate recurrence and mid-term survival of patients with large HCC treated by transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA). METHODS This was a retrospective study. From 2010 to 2013, 46 consecutive patients with large HCC were treated with simultaneous TACE and RFA. Thirty-five of 46 patients had a single tumor. Progression-free survival (PFS) and overall survival (OS) were analyzed at 2 years and 3 years, respectively. RESULTS Forty-six patients treated by simultaneous TACE and RFA had no significant complications and treatment was successful. After 3 years, median PFS and OS were 10.21 ± 1.58 mo and 26.44 ± 2.26 mo, retrospectively. The survival rate was 67.5% after 2 years and 55.67% after 3 years. CONCLUSION These preliminary data show that simultaneous TACE and RFA are safe and effective for large HCC.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignant tumor composed of undifferentiated thyroid follicular cells. Pathological diagnosis of ATC can be challenging as the tumor may show morphological overlap with other neoplasms with anaplastic morphology. Immunohistochemical demonstration of thyroid origin facilitates the diagnosis of ATC. Previous studies using the polyclonal anti-PAX8 antibody 10336-1-AP suggested that PAX8 was the most sensitive marker, expressed in up to 80% of ATC. According to a 2018 NordiQC report, the monoclonal anti-PAX8 antibody MRQ-50 has become the most commonly used anti-PAX8 antibody worldwide. However, validation of this antibody in ATC is lacking. In this study, we recruited 182 ATC cases from seven institutions. Pathology slides were subjected to histology review. PAX8 immunohistochemistry using the MRQ-50 antibody was performed in whole tissue slides (n = 147) or tissue microarray sections (n = 35). We found PAX8 expression in 54.4% of the cases, which was significantly lower than those reported in prior studies with the polyclonal antibody. PAX8 expression was positively correlated with the presence of an epithelial pattern (63.6% vs 37.5%, p = 0.0008) and a coexisting differentiated thyroid carcinoma component (71.6% vs 44.3%, p = 0.0004), but was not associated with age, gender, specimen type, or presence of giant cell and sarcomatoid patterns. In conclusion, we demonstrated PAX8 expression using the monoclonal antibody MRQ-50 in only half of the cases in a large ATC series. Pathologists should be aware that PAX8 expression in ATC is less than those reported in early studies to avoid misdiagnosis.

Objective. To evaluate the safety and efficacy of surgical ligation and endovascular embolization for the treatment of type II congenital extrahepatic portosystemic shunt (CEPS). Methods. In this retrospective study, 23 patients diagnosed with type II CEPS between March 2011 and April 2019 were divided into either a surgical group ( n = 13 ; 41.5 ± 19.9 years) or the interventional group ( n = 10 ; 44.9 ± 19.7 years). The surgical group underwent laparoscopic surgical ligation of the shunt alone or ligation of the shunt and splenic artery and/or vein. The interventional group underwent endovascular embolization using microcoils, detachable coils, and vascular plug. Results. All 23 patients received a one-step shunt closure, and their clinical symptoms were significantly improved within 3-month postprocedure and without recurrence during follow-up. The serum ammonia levels in both groups decreased after the procedure and dropped to normal level at 6- to 12-month postprocedure. Compared with baseline, the portal vein diameter in interventional group increased significantly at 3-, 6-, 12-, and 36-month postocclusion ( P = 0.01 for all). The procedure time was shorter in the interventional group ( 127.0 ± 43.2 minutes) than the surgical group ( 219.8 ± 56.7 minutes; P < 0.001 ). The intraoperative blood loss in the interventional group ( 32.0 ± 62.5 mL) was less than that in the surgical group ( 238.5 ± 396.9 mL; P = 0.001 ). Conclusion. Both surgical ligation and endovascular embolization are effective in the treatment of type II CEPS. Endovascular embolization has the advantages of shorter procedure time and less intraoperative blood loss. The ligation of the portosystemic shunt and splenic artery and vein is feasible with apparent safety, and it could avoid a second surgical treatment.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy that originates in parafollicular cells. It is well-known that a quarter of MTC are involved in hereditary multiple endocrine neoplasia type 2 syndromes, whereas most MTC are sporadic. Unlike the commonly encountered gastrointestinal or pulmonary neuroendocrine tumors, most sporadic MTCs have distinct genetic alterations featured by somatic changes of either Rearranged during Transfection (RET) or RAS point mutation. The increasing application of next-generation sequencing, whole-exome sequencing, and other molecular detection techniques enables us to understand MTC comprehensively concerning its detailed molecular changes and their clinical correlations. This article reviews the advances in genetic alterations and their prognostic impact in sporadic MTC among different populations and discusses the associated tumor immune microenvironments and the potential role of immunotherapy targeting PD-L1/PD-1 in treating MTC. Furthermore, the current multikinase inhibitor targeting therapy for sporadic MTC has been summarized here and its efficacy and drug toxicity are discussed. Updates in advance of the role of calcitonin/procalcitonin/calcitonin-related polypeptide alpha (CALCA) gene transcripts in diagnosing and handling MTC are also mentioned. The treatment of advanced MTC is still challenging and might require a combination of several modalities.

Benign Prostatic Hyperplasia (BPH) is a benign prostate disease based on the benign proliferation of stromal cells and epithelial cells. Due to fibroid hyperplasia and an increase in the glands of the prostate, the entire prostate eventually increases in size [1–4]. In the pathological process of benign prostatic hyperplasia, sex hormones play an important role, the most important of which is the androgen secreted by the testes. Androgen is converted into active dihydrotestosterone (DHT) by type II 5α reductase in the prostate, and DHT also plays an important role in the proliferation of prostate stromal and epithelial cells [5–7].

Advances in medical sciences and evidence-based medicine have led to momentous changes in classification and management of thyroid neoplasms. Much progress has been made toward avoiding overdiagnosis and overtreatment of thyroid cancers. The new 2017 World Health Organization (WHO) classification of thyroid neoplasms updated the diagnostic criteria and molecular and genetic characteristics reflecting the biology and behavior of the tumors, and newly introduced the category of borderline malignancy or uncertain malignant potential. Some neoplasms were subclassified, renamed, or redefined as a specific entity. This review introduces changes in the fourth edition WHO classification of thyroid tumors and updates the contemporary diagnosis and classification of thyroid tumors. We also discuss several challenges with the proposal of new diagnostic entities, since they have unique histopathologic and molecular features and clinical relevance.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed. Terahertz (THz) spectroscopy is considered to have the potential to distinguish between normal liver tissue and HCC tissue; however, there are few reports on it. We conduct this observational study to explore the feasibility of THz imaging for the diagnosis of HCC. Aim To evaluate the feasibility of THz for discriminating between HCC and normal liver tissues using fresh tissue specimens obtained from HCC patients who had undergone surgery. Methods Normal liver tissue and HCC tissue were cryosectioned into 50 μm-thick slices and placed on cover glass. Two adjacent tissue sections were separated subjected to histopathological examination by hematoxylin and eosin staining or THz transmission examination, and THz images were compared with pathologically mapped images. We determined the typical tumor and normal liver tissue regions by pathological examination; the corresponding areas of adjacent sections were examined by THz transmission. Results The transmission rate of HCC tissue was 0.15-0.25, and the transmission rate of typical HCC tissue was about 0.2. THz transmittance in normal liver tissue is slightly higher than 0.4, but there were many influencing factors, including the degree of liver cirrhosis, fat components, ice crystals in frozen sections, and apoptosis. Conclusion In conclusion, this study shows that THz imaging can detect HCC tissue. Further research will yield more detailed data of the THz transmission rates of HCC tissue with different degrees of differentiation.

Purpose To investigate an augmented reality (AR)–guided endovascular puncture to facilitate successful transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods An AR navigation system for TIPS was designed. Three-dimensional (3D) liver models including portal and hepatic vein anatomy were extracted from preoperative CT images. The 3D models, intraoperative subjects, and electromagnetic tracking information of the puncture needles were integrated through the system calibration. In the AR head-mounted display, the 3D models were overlaid on the subjects, which was a liver phantom in the first phase and live beagle dogs in the second phase. One life-size liver phantom and 9 beagle dogs were used in the experiments. Imaging after puncture was performed to validate whether the needle tip accessed the target hepatic vein successfully. Results Endovascular punctures of the portal vein of the liver phantom were repeated 30 times under the guidance of the AR system, and the puncture needle successfully accessed the target vein during each attempt. In the experiments of live canine subjects, the punctures were successful in 2 attempts in 7 beagle dogs and in 1 attempt in the remaining 2 dogs. The puncture time of needle from hepatic vein to portal vein was 5–10 s in the phantom experiments and 10–30 s in the canine experiments. Conclusions The feasibility of AR-based navigation facilitating accurate and successful portal vein access in preclinical models of TIPS was validated.

The extent of neck dissection for patients with papillary thyroid carcinoma (PTC) metastasis in lateral cervical lymph nodes is still debated. Studies aiming to omit level IIb were generally based on postoperative histopathologic information. The purpose of this study was to evaluate the predictive value of fine-needle aspiration (FNA) for level II lymph nodes in identifying candidates for neck dissection sparing level IIb before surgery.We prospectively enrolled 156 consecutive previously untreated PTC patients with lateral neck metastases who were subjected to 178 therapeutic lateral neck dissections (including level IIa, IIb, III, IV, and Vb) between June 2018 and August 2021. Ultrasound-guided FNA of suspicious lymph nodes at level II was preoperatively performed. The cytology of FNA and thyroglobulin (Tg) washout concentration with other clinical predictors was analyzed for lymph node metastases at level IIb.Preoperative ultrasonography revealed suspicious lymph nodes at level II in 118 cases, and fifty were positive on FNA results. Metastasis at level IIb was seen in 17 (9.6%) of the postoperative specimens. By univariate analysis, the rate of level IIb metastasis was significantly higher in patients with FNA-positive lymph nodes at level II (P0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm.Level IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare lymphoma subtype. The present study investigated a refractory nodal ALK-positive LBCL case in a 28-year-old Chinese male. It was initially misdiagnosed as ALK-positive anaplastic large cell lymphoma; however, the patient's lesions relapsed and spread widely following a short remission for chemotherapy and the patient succumbed to the disease 3 months' post-autologous stem cell transplantation; thus, a revision was performed. Histologically, the tumor cells exhibited a characteristic immunoblastic morphology with marked cellular pleomorphism. All lesions shared the same immunoprofiles, including granular cytoplasmic ALK staining patterns and a lack of cell lineage-associated markers, with the exception of cluster of differentiation (CD)45 and CD4. CD30 expression was revealed to be negative and CD138 staining was observed to be positive, additionally, cytokeratin was expressed aberrantly in a relapsed tumor biopsy. Fluorescence in situ hybridization studies demonstrated breakage and extra copies of the ALK gene in ≥30% of cells. Final clarification was provided by the detection of immunoglobulin κ locus (IGK) gene rearrangement in clonality studies [but notimmunoglobulin heavy locus (IGH) and immunoglobulin λ locus (IGL) genes]. This aggressive entity requires distinct modalities of standard treatment, and may be ignored owing to its rarity in routine pathology laboratories. BIOMED-2 polymerase chain reaction assays, including for IGH, IGK and IGL genes, are essential for the detection of gene rearrangement.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignant tumor composed of undifferentiated thyroid follicular cells. Pathological diagnosis of ATC can be challenging as the tumor may show morphological overlap with other neoplasms with anaplastic morphology. Immunohistochemical demonstration of thyroid origin facilitates the diagnosis of ATC. Previous studies using the polyclonal anti-PAX8 antibody 10336-1-AP suggested that PAX8 was the most sensitive marker, expressed in up to 80% of ATC. According to a 2018 NordiQC report, the monoclonal anti-PAX8 antibody MRQ-50 has become the most commonly used anti-PAX8 antibody worldwide. However, validation of this antibody in ATC is lacking. In this study, we recruited 182 ATC cases from seven institutions. Pathology slides were subjected to histology review. PAX8 immunohistochemistry using the MRQ-50 antibody was performed in whole tissue slides (n = 147) or tissue microarray sections (n = 35). We found PAX8 expression in 54.4% of the cases, which was significantly lower than those reported in prior studies with the polyclonal antibody. PAX8 expression was positively correlated with the presence of an epithelial pattern (63.6% vs 37.5%, p = 0.0008) and a coexisting differentiated thyroid carcinoma component (71.6% vs 44.3%, p = 0.0004), but was not associated with age, gender, specimen type, or presence of giant cell and sarcomatoid patterns. In conclusion, we demonstrated PAX8 expression using the monoclonal antibody MRQ-50 in only half of the cases in a large ATC series. Pathologists should be aware that PAX8 expression in ATC is less than those reported in early studies to avoid misdiagnosis.

The authors describe an aptasensor for visual and fluorescent detection of lysozyme via an inner filter effect (IFE). The assay is based on the fact that red gold nanoparticles (AuNPs) act as powerful absorbers of the green fluorescence of CdTe because of spectral overlap. If the lysozyme-binding aptamer is adsorbed onto the surface of the AuNPs, the salt-induced aggregation of AuNPs (that leads to a color change from red to blue) does not occur and the IFE remains efficient. If lysozyme is present, it will bind the aptamer and thereby prevent its adsorption on the AuNPs. As a result, the salt-triggered aggregation of the AuNPs will occur. Consequently, color will change from red to blue, and green fluorescence will pop up because the IFE is suppressed. Under optimum conditions, fluorescence is linearly related to lysozyme concentration in the 1.0 nM to 20 nM concentration range, with a 0.55 nM limit of detection. The method is perceived to be of wider applicability in that it may be used to design other visual and fluorescent assays if appropriate aptamers are available.

Cases with nuclear atypia with or without architectural atypia are classified into low-risk indeterminate (AUS/FLUS, Thy 3a, or TIR 3A), high-risk indeterminate (FN/SFN, Thy 3b, or TIR 3B), suspicious for malignancy (SM), or conclusive (definitive) malignancy (M) categories in most international reporting systems [1–3]. However, this author believes detailed morphological criteria to stratify risk, particularly in borderline/indeterminate cases, are not well established. This was evidenced by the significant variance in actual risk of malignancy (ROM) of AUS/FLUS, FN/SFN, and SM categories on surgical follow-up among reports [4–6] despite efforts to standardize diagnostic criteria in all reporting systems. These ROMs were usually high in Asian practice even with the same reporting system (Bethesda system) [7–9]. ROMs of AUS/FLUS in six institutes representing five (India, Japan, Korea, Taiwan, and Thailand) Asian countries were on average 44.0% (range, 14.3–75%), those of FN/SFN were on average 44.0% (range, 20.9–73.3%), and those of SM were on average 87.4% (range, 75–94.1%) [7–10], which were all significantly higher than estimated ROMs by the first edition Bethesda authors (5–15% for AUS/FLUS, 15–30% for FN/SFN, and 60–75% for SM nodules) [11] and the second edition Bethesda system (ROMs with NIFTP: 6–18% for AUS/FLUS, 10–40% for FN/SFN, and 45–60% for SM nodules) [1]. Possible contributing factors for these differences may be multifactorial, such as different patient series, reporting systems, and clinical management [7, 9]. One more significant contributing factor is the different definition and diagnostic criteria of PTC-N between Western and Asian practices emphasized in Chap. 21 (Please refer to Chap. 21.). Under different definitions and threshold of PTC-N, we cannot expect comparable results for thyroid FNA cytology. Which diagnostic criteria and threshold of PTC-N is chosen for thyroid FNA and surgical pathology practice is a significant factor that determines the ROMs on histology and prevalence of noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) in pathology practice [7]. (Please refer to Chap. 21.)

Purpose: The aim of this study was to evaluate the safety and efficacy of transarterial interventional therapy for the treatment of hepatocellular carcinoma (HCC) patient with peritoneal metastases. Materials and Methods: A total of 7 HCC patients with peritoneal metastases were treated by interventional therapy. Combined treatment with transarterial chemoembolization for intrahepatic lesions and transarterial embolization for peritoneal metastases was performed through hepatic artery, gastroduodenal artery, and superior mesenteric artery. Results: Treatment resulted in an objective response of 85.7% Modified Response Evaluation Criteria in Solid Tumors. No severe adverse effects were observed. Conclusions: Transarterial interventional therapy can be performed safely and may improve the prognosis of HCC patients with peritoneal metastases.

Background Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed. Aim To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor. Methods In this study, a rabbit liver VX2 tumor model was established. After laparotomy, under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis. Results The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue. Conclusion Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.

Background To identify location and number of insulinomas before operation is very important for improving the cure rate. The objective of the study was to assess performance of CT during celiac artery angiography for preoperative localization of clinically suspected small insulinomas (

Background Malignant obstructive jaundice is a common problem in the clinic. Currently, the generally applied treatment methods are percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD). Nevertheless, there has not been a uniform conclusion published on either efficacy of the two types of drainage or the incidence rate of complications. Therefore, we conducted a systematic review and meta-analysis of studies comparing endoscopic versus percutaneous biliary drainage in malignant obstructive jaundice, to determine whether there is any difference between percutaneous and endoscopic biliary drainage, with respect to efficacy and incidence rate of overall complications. Methods The enrolled studies contain a total of three randomized controlled trials and eleven retrospective studies, which together encompass 2246 patients with PTBD and 8100 patients with EBD. Results Our analysis indicates that there is no difference between PTBD and EBD with regard to therapeutic success rate (%), overall complication (%), intraperitoneal bile leak, 30-day mortality, sepsis, or duodenal perforation (%). Cholangitis and pancreatitis after PTBD were lower than after EBD, with odds ratios (OR) of 0.48 (95% confidence interval (CI), 0.31 to 0.74) and 0.16 (95% CI, 0.05 to 0.52), respectively. Incidences of bleeding and tube dislocation for PTBD were higher than EBD, OR of 1.81 (95% CI, 1.35 to 2.44) and 3.41 (95% CI, 1.10 to 10.60). Conclusions This meta-analysis indicates certain advantages for both PTBD and EBD. In the clinical practice, it is advised to choose specifically either PTBD or EBD, based on location of obstruction, purpose of drainage (as a preoperative procedure or a palliative treatment) and level of experience in biliary drainage at individual treatment centers.

The aim of this study is to compare the efficacy and safety of percutaneous radiofrequency ablation (RFA) under general anesthesia or local anesthesia plus intraoperative analgesia in the treatment of hepatocellular carcinoma (HCC) at unusual regions.From July 2012 to October 2019, 83 consecutive patients with 107 HCC lesions were treated with interventional radiology therapy. The lesions were located at some unusual regions such as diaphragmatic surface, hepatic hilum, hepatic subcapsular region, tissues near inferior vena cava, and tissues near the colon. General anesthesia was applied in 57 cases (general anesthesia group) and local anesthesia plus intraoperative analgesia was used in 26 cases (local anesthesia group). All patients were treated with transcatheter arterial chemoembolization, followed immediately by RFA. The rate of tumor inactivation, time used for placing RF needles to the scheduled sites, pain score, and complications were analyzed.All continuous variables were tested for the normal/nonnormal distribution by Kolmogorov-Smirnov test. The t-test was used to analyze the normal distribution variables; the Mann-Whitney U-test was used to measure nonnormal distribution variables; and the Chi-square test for categorical variables. P0.05 was considered statistically significant.The treatments were successful in all patients, including 51 cases of complete response (CR) and 6 cases of partial response (PR) in the general anesthesia group and 18 cases of CR and 8 cases of PR in the local anesthesia group (P = 0.049). The time used for placing the needles to the scheduled sites was 1-5 min (mean 2 min) in the general anesthesia group and 2-9 min (mean 4 min) in the local analgesia group (P0.001). The pain scores ranged from 0 to 2 points (mean 1 point) in the general anesthesia group and 2-9 points (mean 5 points) in the local anesthesia group (P0.001). With regard to complications, seven cases had pneumothorax and four cases had slight hepatic subcapsular hemorrhage in the general anesthesia group and four cases of pneumothorax and three cases of slight hepatic subcapsular hemorrhage in the local anesthesia group, and the difference was not statistically significant between the two groups (P = 0.715).For HCC located at unusual regions, general anesthesia is superior to local anesthesia plus intraoperative analgesia in percutaneous RFA in reducing the difficulty of the procedure and improving the safety of RFA.

The aim of the present study is to investigate the relationship between urinary-type plasminogen activator (uPA) expression and clinicopathological features in papillary thyroid carcinoma (PTC) and to determine the signal transduction of PTC cells in vitro. PTC tissues from 42 patients were analyzed for the expression of uPA and the BRAF(V600E) mutation. BCPAP, a PTC cell line harboring the BRAF(V600E) mutation, was used to study MAPK signaling. PCR and direct sequencing were applied to analyze BRAF(V600E) mutation status. uPA mRNA expression was measured using a quantitative RT-PCR method, and uPA protein was localized using an immunohistochemical method. The ERK protein status was detected by Western blot analysis. uPA gene expression was significantly increased in PTC tissues as compared to the corresponding non-tumor tissues. Furthermore, the up-regulation of uPA mRNAs was correlated with high-risk clinicopathological features, including extrathyroid invasion, loss of cellular polarity/cohesiveness, and the BRAF(V600E) mutation. Marked dephosphorylation of ERK1/2 and down-regulation of uPA expression were detected when BCPAP was treated with a MEK inhibitor, U0126. MEK inhibitors might be a potential treatment strategy for aggressive PTC with BRAF(V600E) through inhibition of uPA expression.

Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1−/PD-1− as type 2 (17%), PD-L1+/PD-1− as type 3 (5%), and PD-L1−/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.

Papillary thyroid carcinoma (PTC) has long been diagnosed based on its unique nuclear features (PTC-N); however, significant observer discrepancies have been reported in the diagnosis of encapsulated follicular patterned lesions (EnFPLs), because the threshold of PTC-N is subjective. An equivocal PTC-N may often occur in non-invasive EnFPLs and benign/malignant disagreements often create serious problems for patients' treatment. This review collects recent publications focusing on the so-called encapsulated follicular variant of papillary thyroid carcinoma (EnFVPTC) and tries to emphasize problems in the histopathological diagnosis of this spectrum of tumors, which covers encapsulated common-type PTC (EncPTC), EnFVPTC, well-differentiated tumor of uncertain malignant potential (WDT-UMP), follicular adenoma (FA) with equivocal PTC-N and minimally invasive follicular carcinoma (mFTC). We propose that EnFVPTC and other EnFPLs with equivocal PTC-N should be classified into a unified category of borderline malignancy, such as well-differentiated tumor of uncertain behavior (WDT-UB), based on their homogeneous excellent outcome. It is suggested that the unified nomenclature of these lesions may be helpful to reduce significant observer disagreements in diagnosis, because complete agreement in the diagnosis of an EncPTC, EnFVPTC or FA by all pathologists may be not possible for this problematic group of tumors. In conclusion, a malignant diagnosis of EnFVPTC should not be used to cover this spectrum of tumors until uncertainty about the nature of this lesion is settled, whether it is benign, precancerous or malignant.

We propose a new classification of thyroid follicular cell tumors which is correlated with patient's prognosis. It is unique as to two new categories: borderline malignancy between benign and malignant, and moderately differentiated adenocarcinoma (MDA) as a differentiation classification to stratify tumor aggressiveness. As to diagnostic criteria, we recommend invasiveness (capsular and vascular invasion) to separate benign and malignant and it should not be based on presence or absence of papillary thyroid carcinoma (PTC) type nuclear features (PTC-N). Thus borderline malignancy in our new classification includes some of the formerly malignant tumors and they are 1) papillary microcarcinoma, 2) encapsulated conventional PTC (EncPTC), 3) encapsulated follicular variant PTC (EnFVPTC), 4) well differentiated tumor of uncertain malignant potential (WDT-UMP), 5) follicular tumors of uncertain malignant potential (FT-UMP), and 6) capsular invasion only follicular thyroid carcinoma (FTC). Review of the literature revealed that those thyroid tumors have consistently excellent outcome. Well differentiated follicular cell adenocarcinoma (WDA) in our classification includes common type PTC and low-risk follicular carcinoma (FTC). They are invasive (diffuse infiltrative) common type PTC and minimally invasive type FTC with less than 4 foci of angioinvasion. Moderately differentiated follicular cell adenocarcinoma (MDA) includes FTC with angioinvasion (more than 4), aggressive variants of PTC, such as tall cell, columnar cell, solid, loss of cellular polarity/cohesiveness (hobnail) variants and encapsulated carcinoma with high grade histology. Poorly differentiated carcinoma (PDC) includes PDC of WHO definition, insular carcinoma, tumors with minor anaplastic transformation and tumors with distant metastasis at presentation.

Squamous cells in the thyroid appear in a variety of conditions, including adenomatous goiters, malignant neoplasms, inflammatory diseases, and embryonic remnants. However the origin of the squamous cells is still under dispute. Here we report a case of an encapsulated follicular cell tumor consisting of follicular cells, basaloid squamous cells, and morphologically intermediate cells. The patient was a 66-year-old man presenting with a progressively enlarged painless lump in the right side of his neck. A solid tumor with encapsulation in the right lobe was confirmed by simple right lobe thyroid lobectomy. This tumor demonstrated heterogeneous immunoreactions for Ki-67, thyroglobulin, thyroid transcription factor-1, and pan-cytokeratin (AE1/AE3), in that the intermediate cells had intermediate immunoreactivity between follicular and basaloid squamous cells. p63 was positive in the periphery layer of tumor cell nests of the intermediate and squamous cells. A completely negative immunoreaction was noted for high molecular weight cytokeratin (34βE12), calcitonin, CEA, p53, CD5, and rearranged in transformation (RET). Mutational analysis of BRAF and RAS were negative. These results strongly suggest that this tumor is a follicular adenoma, and that the squamous component originated from follicular cells undergoing squamous metaplasia. The patient has been disease free more than 40 months after surgery.

Periostin is an extracellular matrix protein. Five isoforms of human periostin cDNA have been reported, but the expression of periostin isoforms in the human thyroid tissue is by far unknown. A group of primer sets were designed to amplify the full length of cDNA sequence of periostin. Using human thyroid carcinoma and their paired non-neoplastic tissues together with anaplastic thyroid carcinoma cell lines, we examined the presence of periostin cDNA isoforms by RT-PCR and direct DNA sequence analysis. We identified eight coexisting cDNA isoforms in all the tissue samples and cell lines. Three of them were unique to this study. Especially two of them haven't been previously reported in any species. The eight periostin isoforms differ in the C-terminus from exon XII to exon XXI where alternative splicing usually happens. This is the first report that demonstrates all the eight isoforms of periostin cDNA expressed in the human thyroid gland and identifies three novel isoforms.

Summary Background & aims We examined the effects of a coffee preparation on liver fibrosis induced by carbon tetrachloride (CCl 4 ) and explored the possible mechanisms. Methods Rats were divided randomly into four groups: control, CCl 4 , and two coffee preparation groups. Except for the control group, liver fibrosis was induced in male Sprague–Dawley (SD) rats by subcutaneous injection with 40% CCl 4 twice a week for 8 weeks. At the same time, a coffee preparation (300 mg/kg and 150 mg/kg) was administered to the two coffee preparation groups intragastrically once daily. Results Upon pathological examination, a coffee preparation treatment significantly reduced liver damage and symptoms of liver fibrosis. The mRNA expression of collagen I, collagen III, bcl-2, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) were markedly increased by CCl 4 treatment but suppressed by a coffee preparation treatment. Whereas compared with the CCl 4 group, the mRNA expression of Bax was increased in the coffee preparation group. The protein expression of Bax and bcl-2 were confirmed by western blot. Intragastric administration of a coffee preparation reduced the protein expression of α-smooth muscle actin (α-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl 4 . Conclusions Our data indicate that a coffee preparation can efficiently inhibit CCl 4 -induced liver fibrosis in rats. The coffee preparation may therefore be a potential functional food for preventing liver fibrosis.

We report the case of a common type papillary thyroid carcinoma (PTC) patient who developed early recurrence and persistent disease even after ablation therapy. The patient was an 80-year-old man that was incidentally found to have a mass lesion in the left lower lobe of his thyroid. A total thyroidectomy and a left side modified radical neck dissection were performed; histological examination revealed a common type PTC. The patient underwent lymph node dissection twice for recurrence and (131)I-Na ablations for fluctuated elevation of serum thyroglobulin. The resected tumor and recurrence in lymph nodes revealed non-solid type papillary carcinoma with mixed features of less well-differentiated morphology, which we suggest included loss of cellular polarity/cohesiveness, tall cells and columnar cells. Immunohistochemistry revealed high a MIB-1 labeling index (15-20%) in both the primary tumor and the metastatic tumor in the lymph nodes. p53 immunoreaction was found positive at very low level (

The presence of calcification is the most significant ultrasonographic finding in evaluating thyroid nodules. Calcifications are more frequently detected in papillary thyroid carcinoma than in other thyroid lesions. However, the clinical significance of calcification, including clinical correlations and impact on survival, and the molecular mechanism responsible for calcification in papillary thyroid carcinoma remain uncertain. We performed a retrospective study of patients with primary common-type papillary thyroid carcinoma to determine the clinical correlations of calcification and its impact on survival. Histologically, calcification was classified as either psammoma bodies, stromal calcification, or bone formation. They were identified in 25, 47, and 13% of all 229 cases of papillary thyroid carcinoma, respectively. The presence of psammoma bodies was significantly correlated with gross lymph node metastasis and stage grouping. Both stromal calcification and bone formation were significantly correlated with patient age. In addition, stromal calcification was associated with pT classification and gross lymph node metastasis. Papillary thyroid carcinoma with, compared to that without, psammoma bodies was associated with poorer disease-free survival. We examined the quantitative expression of BMP-1, a metalloproteinase that is reported to be involved in bone and extracellular matrix formations, and found that its expression was significantly higher in tumors with psammoma bodies or with stromal calcification (P=0.0464 and 0.0272, respectively). These results suggest that the presence of psammoma bodies is a useful predictor of outcome for patients suffering from papillary thyroid carcinoma.

Prognostic analyses of thyroid carcinomas of follicular cell origin were carried out on patients treated at Kuma Hospital, Kobe, Japan. A new histopathological classification based on the prognostic evidence is proposed in this study, and it is applicable to the patients treated curatively. Major histological types of papillary carcinoma, follicular carcinoma and poorly differentiated carcinoma were combined into one single entity of follicular cell adenocarcinoma because (i) they have the same cell origin (follicular cell); (ii) clear-cut separation of papillary and follicular carcinoma is not always possible, and 10 year cause-specific survival was essentially similar when the patients were treated curatively; and (iii) poorly differentiated carcinoma usually has a background of either papillary or follicular carcinoma. This adenocarcinoma together with undifferentiated carcinoma was stratified into four prognostic groups using pure morphological criteria of the degree of cellular differentiation and histological grade. They are termed well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, poorly differentiated carcinoma and undifferentiated carcinoma of the thyroid. The 10 year disease-free survival rates were 86.3-93.1%, 65.4-78.7%, and 43.0-53.8%, and 0%, respectively. The 10 year cause-specific survival rates were 97.2-100%, 91.5-97.4%, and 71.2-80.0%, and 0%, respectively.

To investigate the clinicopathologic characteristics, prognosis and histologic origin of the mucinous tumor of the peritoneum.According to 2010 WHO classification of tumours of the digestive system, 34 cases diagnosed as "pseudomyxoma peritonei (PMP) " were reevaluated and divided into low grade and high grade. Immunohistochemistry was applied to investigate the expression of SATB2 and the histologic origin of the mucinous tumor of the peritoneum, using antibodies against SATB2, CK7, CK20 and CDX-2. The relationship between clinicopathologic characteristics and prognosis of the low grade and high grade tumors were analyzed.Twenty five patients had low grade mucinous tumors (two of them were no cell type), nine patients had high grade mucinous tumors. There was no significant difference between low grade and high grade mucinous tumors in age, sex, recurrence and organs involvement (P0.05). Thirty patients were followed up, the overall survival rates of patients with low grade and high grade mucinous tumors were 13/21 (61.9%) and 3/9, respectively. The median survival time was 74 and 24 months in low and high grade patients, and the difference was statistically significant (P=0.002).Immunohistochemistry showed the expression rates of CDX-2, CK20, and CK7 in totally 32 cases (excluding 2 cases of no cell type) were 30/32(93.8%), 31/32 (96.9%), and 3/16, respectively; the expression rates of CDX-2, CK20, and CK7 in 16 cases with distinct primary site were 15, 16, and 1, respectively; fifteen of 16 cases of tumors of unknown primary site were positive for CDX-2 and CK20, two of the them were positive for CK7. There was no difference in the expression of CDX-2, CK20 and CK7 between tumors with distinct primary site and tumors with unknown primary site (P0.05). The expression rate of SATB2 in the cases was 56.3% (18/32), excluding 2 cases of no cell type. There was no significant difference between low grade and high grade tumors in the expression of SATB2 [15/23(65.2%) vs 3/9, P=0.102], also SATB2 was not related to the prognosis of the tumor (P=0.786).The prognosis of the mucinous tumor of the peritoneum was significantly different between low grade and high grade according to WHO 2010 classification, and most mucinous tumor of the peritoneum originated from the appendix.

Aims: The aim of this study is to evaluate efficacy and safety of transarterial chemoembolization (TACE) with N-butyl 2-cyanoacrylate (NBCA) for the treatment of hepatocellular carcinoma (HCC) with arterioportal shunts (APS). Subjects and Methods: From January 2008 to June 2014, 36 cases of HCC with APS were treated by TACE with NBCA. NBCA-lipiodol mixture was superselective delivered before routine TACE in HCC patients with APS. Recanalization of shunt, objective response, clinical adverse events, and survival rates was retrospectively studied. Results: All interventional procedures were successful without any procedure relevant complications. The immediate APS improvement rate was 83.3% (30/36), and the APS improvement rate at first-time follow-up was 66.6% (20/30). Radiologically confirmed complete response (CR), partial response, stable disease, and progressive disease at 1 month after first chemoembolization were observed in 1 (2.7%), 19 (52.8%), 6 (16.7%), and 10 (27.8%) patients, respectively. Survival rates were 91.7% at 6 months, 47.2% at 1 year, and 13.9% at 2 years. The median survival time was 11 months. No severe adverse effects were noted. Conclusions: The preliminary experience indicates TACE with NBCA can be safely performed and may improve prognosis of HCC with arterioportal shunt.