Exploring prognostic values of DNA ploidy, stroma-tumor fraction and nucleotyping in stage II colon cancer patients.

PURPOSE: To assess the prognostic value of three novel biomarkers, DNA ploidy, stroma-tumor fraction, and nucleotyping, seeking for more accurate stratification in stage II colon cancer. METHODS: A total of 417 patients with complete follow up information were enrolled in this study and divided into three clinical risk groups. IHC was performed to examine MSI status. DNA ploidy, stroma and nucleotyping were estimated using automated digital imaging system. Kaplan-Meier survival curves, Cox proportional hazards regression models, and correlation analyses were carried out to process our data. RESULTS: In the whole cohort of stage II colon cancer, nucleotyping and DNA ploidy were significant prognostic factors on OS in univariate analyses. The combination of nucleotyping and DNA ploidy signified superior OS and DFS. Difference was not significant between low-stroma and high-stroma patients. In multivariable analyses, nucleotyping and the combination of nucleotyping and DNA ploidy were proven the dominant contributory factors for OS. In the low-risk group, we found the combination of nucleotyping and DNA ploidy as the independent prognostic factor statistically significant in both univariate and multivariable, while in the high-risk group, the nucleotyping. CONCLUSIONS: Our study has proven nucleotyping and the combination of DNA ploidy and nucleotyping as independent prognostic indicators, thus expanding the application of nucleotyping as a predictor from high risk stage II colon cancer to whole risks.

CT2X-IRA: CT to x-ray image registration agent using domain-cross multi-scale-stride deep reinforcement learning.

Objective.In computer-assisted minimally invasive surgery, the intraoperative x-ray image is enhanced by overlapping it with a preoperative CT volume to improve visualization of vital anatomical structures. Therefore, accurate and robust 3D/2D registration of CT volume and x-ray image is highly desired in clinical practices. However, previous registration methods were prone to initial misalignments and struggled with local minima, leading to issues of low accuracy and vulnerability.Approach.To improve registration performance, we propose a novel CT/x-ray image registration agent (CT2X-IRA) within a task-driven deep reinforcement learning framework, which contains three key strategies: (1) a multi-scale-stride learning mechanism provides multi-scale feature representation and flexible action step size, establishing fast and globally optimal convergence of the registration task. (2) A domain adaptation module reduces the domain gap between the x-ray image and digitally reconstructed radiograph projected from the CT volume, decreasing the sensitivity and uncertainty of the similarity measurement. (3) A weighted reward function facilitates CT2X-IRA in searching for the optimal transformation parameters, improving the estimation accuracy of out-of-plane transformation parameters under large initial misalignments.Main results.We evaluate the proposed CT2X-IRA on both the public and private clinical datasets, achieving target registration errors of 2.13 mm and 2.33 mm with the computation time of 1.5 s and 1.1 s, respectively, showing an accurate and fast workflow for CT/x-ray image rigid registration.Significance.The proposed CT2X-IRA obtains the accurate and robust 3D/2D registration of CT and x-ray images, suggesting its potential significance in clinical applications.

Deep learning prediction model for central lymph node metastasis in papillary thyroid microcarcinoma based on cytology.

Controversy exists regarding whether patients with low-risk papillary thyroid microcarcinoma (PTMC) should undergo surgery or active surveillance; the inaccuracy of the preoperative clinical lymph node status assessment is one of the primary factors contributing to the controversy. It is imperative to accurately predict the lymph node status of PTMC before surgery. We selected 208 preoperative fine-needle aspiration (FNA) liquid-based preparations of PTMC as our research objects; all of these instances underwent lymph node dissection and, aside from lymph node status, were consistent with low-risk PTMC. We separated them into two groups according to whether the postoperative pathology showed central lymph node metastases. The deep learning model was expected to predict, based on the preoperative thyroid FNA liquid-based preparation, whether PTMC was accompanied by central lymph node metastases. Our deep learning model attained a sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and accuracy of 78.9% (15/19), 73.9% (17/23), 71.4% (15/21), 81.0% (17/21), and 76.2% (32/42), respectively. The area under the receiver operating characteristic curve (value was 0.8503. The predictive performance of the deep learning model was superior to that of the traditional clinical evaluation, and further analysis revealed the cell morphologies that played key roles in model prediction. Our study suggests that the deep learning model based on preoperative thyroid FNA liquid-based preparation is a reliable strategy for predicting central lymph node metastases in thyroid micropapillary carcinoma, and its performance surpasses that of traditional clinical examination.

Pathologic complete response after neoadjuvant v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibition combined with immunotherapy therapy for anaplastic thyroid carcinoma: a case report and literature review.

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.

Using Whole Slide Gray Value Map to Predict HER2 Expression and FISH Status in Breast Cancer.

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.

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer.

Background: Adenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC. Methods: We applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information. Results: A total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity. Conclusion: This study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.

Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population.

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.

3cDe-Net: a cervical cancer cell detection network based on an improved backbone network and multiscale feature fusion.

BACKGROUND: Cervical cancer cell detection is an essential means of cervical cancer screening. However, for thin-prep cytology test (TCT)-based images, the detection accuracies of traditional computer-aided detection algorithms are typically low due to the overlapping of cells with blurred cytoplasmic boundaries. Some typical deep learning-based detection methods, e.g., ResNets and Inception-V3, are not always efficient for cervical images due to the differences between cervical cancer cell images and natural images. As a result, these traditional networks are difficult to directly apply to the clinical practice of cervical cancer screening. METHOD: We propose a cervical cancer cell detection network (3cDe-Net) based on an improved backbone network and multiscale feature fusion; the proposed network consists of the backbone network and a detection head. In the backbone network, a dilated convolution and a group convolution are introduced to improve the resolution and expression ability of the model. In the detection head, multiscale features are obtained based on a feature pyramid fusion network to ensure the accurate capture of small cells; then, based on the Faster region-based convolutional neural network (R-CNN), adaptive cervical cancer cell anchors are generated via unsupervised clustering. Furthermore, a new balanced L1-based loss function is defined, which reduces the unbalanced sample contribution loss. RESULT: Baselines including ResNet-50, ResNet-101, Inception-v3, ResNet-152 and the feature concatenation network are used on two different datasets (the Data-T and Herlev datasets), and the final quantitative results show the effectiveness of the proposed dilated convolution ResNet (DC-ResNet) backbone network. Furthermore, experiments conducted on both datasets show that the proposed 3cDe-Net, based on the optimal anchors, the defined new loss function, and DC-ResNet, outperforms existing methods and achieves a mean average precision (mAP) of 50.4%. By performing a horizontal comparison of the cells on an image, the category and location information of cancer cells can be obtained concurrently. CONCLUSION: The proposed 3cDe-Net can detect cancer cells and their locations on multicell pictures. The model directly processes and analyses samples at the picture level rather than at the cellular level, which is more efficient. In clinical settings, the mechanical workloads of doctors can be reduced, and their focus can be placed on higher-level review work.

Level IIb neck dissection guided by fine-needle aspiration for N1b papillary thyroid carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P<0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm. CONCLUSIONS: Level IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Expression and Significance of AQP3 in Cutaneous Lesions.

Aquaporin 3 (AQP3) is the membrane channel of water and involved in fluid homeostasis. The aim of this study was to reveal the expression and significance of AQP3 in cutaneous lesions. We analyzed AQP3 mRNA levels using RT-PCR in 311 cutaneous lesions and confirmed AQP3 expression in these lesions by immunohistochemistry. AQP3 mRNA was detected in normal epidermis, seborrheic keratosis, solar keratosis, Bowen's disease, squamous cell carcinoma, eccrine poroma, apocrine carcinoma, and sebaceoma; however, AQP3 mRNA was absent in basal cell carcinoma, nevocellular nevus, or malignant melanoma. By immunohistochemistry, diffuse AQP3 expression was seen in all keratotic lesions including seborrheic keratosis, verruca vulgaris, molluscum contagiosum, solar keratosis, Bowen's disease, and squamous cell carcinoma. Diffuse AQP3 expression was also present in all extramammary Paget's disease. No AQP3 staining was obtained in basal cell carcinoma. Positive AQP3 staining was seen in sweat gland tumors including hidradenoma, eccrine poroma, and apocrine carcinoma. Among sebaceous tumors, AQP3 expressed diffusely in all sebaceous hyperplasia and sebaceous adenoma, but not in sebaceous carcinomas. Only focal AQP3 staining was seen in nevocellular nevus and no AQP3 staining in melanoma. Our findings indicate the function of AQP3 maintained in most skin tumors. AQP3 may be used for differential diagnosis in skin tumors.

Efficacy and Safety of Surgical Ligation versus Endovascular Embolization for Type II Congenital Extrahepatic Portosystemic Shunt.

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.

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery-Risk stratification of papillary thyroid carcinoma in young patients.

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 and <30%, >5 and <10%, 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.

Localized ALK-positive histiocytosis in a Chinese woman: report of a case in the lung with a novel EML4-ALK rearrangement.

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.

Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4.

BACKGROUND: Insulin gene enhancer protein 1, (ISL1), a LIM-homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis. METHODS: We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction (PCR). Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown. RNA-sequencing was performed to identify differentially expressed genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) to reveal key signaling pathways likely regulated by ISL1 in GC. Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) and by detecting glucose consumption and lactate production. The expression of glucose transporter 4 (GLUT4) and ISL1 was assessed by Western blotting, immunohistochemistry, and immunofluorescent microscopy. The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4. RESULTS: High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients. ISL1 knockdown inhibited cell proliferation both in vitro and in vivo. KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown, which was validated by reduced glucose uptake and lactate production, decreased ECAR, and increased OCR. Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter. CONCLUSION: ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.

Cytomorphologic features as predictors of aggressiveness in patients with pT1 papillary thyroid carcinoma: a retrospective study of associations with clinicopathological parameters in 226 fine-needle aspirates.

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<0.001), and the amount of cytoplasm can also predict LNM (P=0.024). CONCLUSIONS: Cytomorphologic features including cellular adhesiveness and the amount of cytoplasm in preoperative FNAC smears could be a valuable tool for predicting ECI or LNM and may be predictors of aggressiveness in patients with pT1 PTC.

Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification.

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.

Feasibility of Augmented Reality-Guided Transjugular Intrahepatic Portosystemic Shunt.

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.

Updates in the advances of sporadic medullary thyroid carcinoma: from the molecules to the clinic.

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.

AQP2 as a diagnostic immunohistochemical marker for pheochromocytoma and/or paraganglioma.

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.

Covered stent placement for hepatic artery pseudoaneurysm.

PURPOSE: To evaluate the efficacy and safety of covered stent placement for the treatment of hepatic artery pseudoaneurysm (HAP). METHODS: Between March 2006 and March 2019, 17 consecutive patients underwent emergency covered stent placement for treatment of HAP. There were 12 men and 5 women aged 24-71 years, with an average age of 49.4 years. Eleven patients had undergone Whipple procedure, 3 had hepatic abscess following hepatectomy, 2 had undergone hepatectomy under extracorporeal circulation, and 1 had received surgical exploration after a car accident. The average interval from surgical intervention to massive bleeding was 15.3 days (range: 6-35 days). After HAP was confirmed by angiography, 1-3 covered stent grafts (3-8 mm in diameter and 13 mm-5 cm in length) were implanted. Adequate drainage, anti-infection treatment, and symptomatic treatment were offered after stent placement, and no anticoagulation or antiplatelet drug was used. RESULTS: The interventions were successful in all 17 patients. Angiography revealed pseudoaneurysms in common hepatic artery in 16 patients (in gastroduodenal artery stumps in 4 patients) and hemorrhage from a ruptured right hepatic artery in 1 patient. All patients were successfully implanted with 1-3 covered stent grafts. Bleeding was completely controlled in 12 patients (stent diameter: 4.5-8 mm). Four patients (stent diameter: 3-4.5 mm) experienced bleeding recurrence 1 h to 3 days after stent implantation, and type 1 endoleaks were identified during second angiography. Finally, these 4 patients died of multiple organ failure 2-10 days after embolization/blockage. The remaining patient suffered from abdominal hemorrhage again 2 weeks after stent implantation, and second angiography showed hemorrhage from a branch of the superior mesenteric artery; no bleeding occurred after embolization. Thirteen patients survived at discharge, and the average length of hospital stay was 26.53 days (range: 11-58 days). The average follow-up time was 23 months (range: 16-37 months), during which 6 patients died of tumor progression. No bleeding recurred during the follow-up period, and routine color Doppler ultrasound revealed that the common hepatic artery was patent and the blood flow was smooth at the stent implantation site. CONCLUSION: Covered stent placement is a safe and effective alternative for treating HAP patients with high risk of severe complications after hepatic artery embolization. Larger stent grafts (> 4 mm in diameter) may achieve better prognosis.