Poly (ADP-ribose) polymerase-1 (PARP-1) is a good prognostic marker for pancreatic/periampullary cancers.

BACKGROUND: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerases-1 (PARP-1) have emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well. METHODS: We assessed the prognostic significance of PARP1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray. RESULTS: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers (P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses (P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers. CONCLUSIONS: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A standardized pathology report for gastric cancer: 2nd edition.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Tumor Budding as a Marker for Poor Prognosis and Epithelial-Mesenchymal Transition in Lung Cancer: A Systematic Review and Meta-Analysis.

Introduction: Currently, tumor budding (TB) is considered to predict the prognosis of patients. The prognostic significance of TB has also been explored in patients with lung cancer, but has not been fully clarified. In the present meta-analysis, we evaluated the prognostic significance, clinicopathological value, and relationship with epithelial-mesenchymal transition (EMT) of TB in lung cancer. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched up to July 7, 2021, for the relevant articles that showed the relationship between TB and prognosis in patients with lung cancer. For statistical analysis, we used pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) to assess the correlation between high-grade TB expression and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), clinicopathological factors, and EMT markers. Results: A total of 3,784 patients from 10 independent studies were included in the statistical analysis. Our results indicated that high-grade TB was significantly associated with poor OS [HR 1.64 (95% CI, 1.43-1.87)] and DFS [HR 1.65 (95% CI, 1.22-2.25)]. In terms of clinicopathological characteristics, high-grade TB was associated with larger tumor size, higher T and N stage, pleural invasion, vascular invasion, lymphatic invasion, and severe nuclear atypia. Interestingly, smoking showed significant association with high-grade TB, despite the fact that previous studies could not show a significant relationship between them. Furthermore, through our systematic analysis, high-grade TB showed a significant relationship with EMT markers. Conclusion: Our findings indicate that high-grade TB is associated with a worse prognosis in patients with lung cancer. TB evaluation should be implemented in routine pathological diagnosis, which may guide the patient's treatment.

Distinct genomic profiles of gestational choriocarcinoma, a unique cancer of pregnant tissues.

Little is known about genomic alterations of gestational choriocarcinoma (GC), unique cancer that originates in pregnant tissues, and the progression mechanisms from the nonmalignant complete hydatidiform mole (CHM) to GC. Whole-exome sequencing (20 GCs) and/or single-nucleotide polymorphism microarray (29 GCs) were performed. We analyzed copy-neutral loss-of-heterozygosity (CN-LOH) in 29 GCs that exhibited androgenetic CN-LOHs (20 monospermic, 8 dispermic) and no CN-LOH (one with NLRP7 mutation). Most GCs (25/29) harboring recurrent copy number alterations (CNAs) and gains on 1q21.1-q44 were significantly associated with poor prognosis. We detected five driver mutations in the GCs, most of which were chromatin remodeling gene (ARID1A, SMARCD1, and EP300) mutations but not in common cancer genes such as TP53 and KRAS. One patient's serial CHM/invasive mole/GC showed consistent CN-LOHs, but only the GC harbored CNAs, indicating that CN-LOH is an early pivotal event in HM-IM-GC development, and CNAs may be a late event that promotes CHM progression to GC. Our data indicate that GCs have unique profiles of CN-LOHs, mutations and CNAs that together differentiate GCs from non-GCs. Practically, CN-LOH and CNA profiles are useful for the molecular diagnosis of GC and the selection of GC patients with poor prognosis for more intensive treatments, respectively.

Efficacy of Endobiliary Radiofrequency Ablation using a Novel Endoluminal Radiofrequency Ablation Catheter in a Swine Model.

Purpose: Endobiliary radiofrequency ablation (RFA) is a new endoscopic ablative technique. However, the ideal power setting for RFA has not yet been clarified. Therefore, we intended to evaluate the effects of endobiliary RFA according to time variations using novel RFA. Materials and methods: Nine female pigs were divided into three groups according to ablation time (60, 90, and 120 seconds) with the same setting (10 watts, 80 °C). All pigs underwent endoscopic retrograde cholangiography (ERC) and endobiliary RFA in the common bile duct. Gross and histologic examinations were performed after 24 hours. Results: The ERC and application of the endobiliary RFA were 100% successful, and the post-RFA cholangiogram did not show contrast leakage. The median depth of microscopic ablation was significantly different among the three groups (60 vs. 90 vs. 120 seconds = 1.90 (1.17-2.23) vs. 2.44 (2.31-2.60) vs. 2.52 (2.47-2.64) mm, p = 0.018). There was also a linear relationship between ablation time and microscopic ablation depth (r2 = 0.552, p = 0.002). However, no significant differences in macroscopic or microscopic ablation length were observed. In addition, there were focal ablation injuries in adjacent liver tissue in five of the nine pigs (2/3 in 60, 1/3 in 90, and 2/3 in 120 seconds). Conclusion: Endobiliary RFA using a novel RFA catheter resulted in controlled ablation with a linear relationship between microscopic ablation depth and ablation time in a swine model. Clinical studies are needed to validate the safe energy condition of endobiliary RFA in malignant biliary obstruction.

Factors to improve the interobserver agreement for gastric atrophy and intestinal metaplasia: consensus of definition and criteria.

AIMS: Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used for these parameters, but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of the consensus process on the assessment of intestinal metaplasia and atrophy. METHODS AND RESULTS: Two study sets were used: consensus and validation. The consensus set was circulated and five gastrointestinal pathologists evaluated them independently using the updated Sydney system. The consensus of the definitions was then determined at the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardise the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through the consensus process (intestinal metaplasia: baseline κ = 0.52 versus final κ = 0.68, P = 0.006; atrophy: baseline κ = 0.19 versus final κ = 0.43, P < 0.001). Higher interobserver agreement in atrophy was observed after consensus regarding the definition (pre-consensus: κ = 0.19 versus post-consensus: κ = 0.34, P = 0.001). There was improved interobserver agreement in intestinal metaplasia after standardisation of the grading criteria (pre-standardisation: κ = 0.56 versus post-standardisation: κ = 0.71, P = 0.010). CONCLUSIONS: This study suggests that interobserver variability regarding intestinal metaplasia and atrophy may result from lack of a precise definition and fine criteria, and can be reduced by consensus of definition and standardisation of grading criteria.

Gastroenteropancreatic-origin neuroendocrine carcinomas: Three case reports with favorable responses following localized radiotherapy and a review of literature.

RATIONALE: The radiotherapy (RT) responses of gastroenteropancreatic (GEP)-origin neuroendocrine tumors remain unclear. We report cases of favorable response after localized RT of GEP-origin neuroendocrine carcinomas (GEP-NECs). PATIENT CONCERNS: 1. An 82-year-old male presented with a lower esophageal mass. Positron emission tomography computed tomography (PET-CT) scan showed a lower esophageal mass and gastrohepatic lymph nodes. 2. A 52-year-old female presented with abdominal discomfort. CT scan showed a 9.8 cm-sized enhancing mass in the lesser sac abutting the stomach, pancreas and liver. 3. A 54-year-old male patient presented with anal pain and bleeding. CT scan showed a remnant mass in the perirectal area after trans-anal excision. DIAGNOSES: The diagnoses of GEP-NECs were pathologically confirmed by biopsy or excision, and immunohistochemical stainings of Ki-67, CD56, synaptophysin and chromogranin-A. INTERVENTIONS: 1. The patient was treated with definitive RT. 2. The patient was treated with RT after two cycles of etoposide-cisplatin chemotherapy. 3. The patient was treated with adjuvant RT. OUTCOMES: 1. Complete remission was achieved based on CT scan four months after RT. 2. CT scan showed partial regression of the mass with a 5 cm-diameter at six months after RT. Adjuvant chemotherapy was administered after RT. 3. The residual mass was almost completely regressed at CT scan four months after RT. LESSONS: In cases of GEP-NECs, RT can be a useful treatment modality with favorable tumor response for patients with inoperable conditions or those suffering from bulky tumor masses.

Successful thoracoscopic resection of a large mediastinal angiomyolipoma.

An angiomyolipoma (AML) is a benign mesenchymal tumor characterized by proliferation of mature vessels, smooth muscle, and adipose tissue. AMLs most commonly occur in the kidney but have been reported in a variety of extrarenal sites. Mediastinal AMLs are extremely rare. We herein present a case of a large AML of the mediastinum that was successfully treated by thoracoscopic resection.

Clinical Outcomes of Endoscopic Removal in Patients with Colorectal Polypoid Leiomyomas.

BACKGROUND/AIMS: Although polypoid leiomyomas in the colon and rectum are rare, they are increasingly detected during colonoscopy. The aim of this study was to evaluate the efficacy and clinical outcomes of endoscopic removal for colorectal polypoid leiomyoma. METHODS: Data were retrospectively collected from 22 patients with polypoid leiomyoma arising from the muscularis mucosae in the colon and rectum who underwent endoscopic removal at single referral gastrointestinal endoscopy unit. Colonoscopic findings, endoscopic removal, success rates, complication rates (bleeding or perforation), pathologic characteristics, and recurrence rates were investigated. RESULTS: Most polypoid leiomyomas were small asymptomatic lesions less than 1 cm. The tumors were located predominantly in the left colon. Ten leiomyomas were removed using cold biopsy forceps, and 12 were resected by conventional polypectomy or endoscopic mucosal resection. All tumors arose from or involved the muscularis mucosa. There were no complications, such as bleeding or perforation. No local remnant lesions were found in 19 patients who underwent at least one follow-up colonoscopy. CONCLUSIONS: This case series represent cases of small colorectal polypoid leiomyoma that were safely removed endoscopically. An awareness of their endoscopic and clinic-pathological characteristics may provide safe treatment strategy for colonic leiomyomatous tumors of similar size in capable hands.

Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung.

Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and ß-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent ß-catenin mutations (overall 3 of 68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Because the AKT1 mutations were not found to co-occur with ß-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be the single-most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas, including a high rate of AKT1 mutation in PSHs. These genomic features of PSH identified in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors.

Anemia resolved by thoracoscopic resection of a mediastinal mass: a case report of unicentric Castleman's disease.

Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder that usually presents as a single or multiple mediastinal mass. In unicentric CD, constitutional symptoms are rare, but are curable with surgical resection. However, serious intraoperative bleeding often requires conversion to thoracotomy. We present a case of unicentric CD in a 25-year-old woman with anemia, who was successfully treated by thoracoscopic resection. We describe the clinical course from the initial presentation to diagnosis and surgical cure.

Clinicopathological Characteristics of Serrated Polyposis Syndrome in Korea: Single Center Experience.

Background/Aim. Serrated polyposis syndrome (SPS) is a rare condition characterized by multiple serrated polyps throughout the colon and rectum. The aim of this study was to evaluate the clinicopathological characteristics of SPS in Koreans. Methods. This retrospective analysis of prospectively collected data was performed using information from the endoscopy, clinical records, and pathology database system of Uijeongbu St. Mary's Hospital. Consecutive patients satisfying the updated 2010 World Health Organization criteria for SPS between June 2011 and May 2014 were enrolled. Results. Of the 17,552 patients who underwent colonoscopies during the study period, 11 (0.06%) met the criteria for SPS. The mean age of these patients was 55.6 years. Ten patients (91%) were males. None had a family history of CRC or a first-degree relative with SPS. Seven patients (64%) had synchronous advanced adenoma. One patient had coexistence of SPS with CRC that was diagnosed at the initial colonoscopy. Five patients (45%) had more than 30 serrated polyps. One of the patients underwent surgery and 10 underwent endoscopic resection. Conclusion. The prevalence of SPS in this study cohort was comparable to that in Western populations. Considering the high risk of CRC, correct diagnosis and careful follow-up for SPS are necessary.

A case of pulmonary metastasis of giant cell tumor of bone presenting as pulmonary arteriovenous malformation.

Although giant-cell tumor (GCT) of the bone was originally classified as a benign tumor, metastasis has been reported. The radiographic features usually comprise parenchymal solitary or multiple nodules that are round-to-oval nodular opacities of homogeneous density in patients with GCT. However, the patient described in this case presented with a hypervascular mass with feeding vessels and hemothorax, which are common features of pulmonary arteriovenous malformation. To the best of our knowledge, cases of pulmonary metastases presenting as a pulmonary arteriovenous malformation have not been reported. Here, we report a case of giant-cell tumor of the bone that exhibited histologically benign pulmonary metastases and mimicked an arteriovenous malformation.

C-Kit-Negative Gastrointestinal Stromal Tumor in the Stomach.

C-kit-negative gastrointestinal stromal tumors (GISTs) are uncommon, and there have been few reports about the diagnosis and treatment of c-kit-negative GISTs in the stomach. We report the case of a patient who was diagnosed with a huge and atypical GIST in the stomach. The GIST was completely resected and finally diagnosed as c-kit-negative GIST based on immunohistochemical staining of tumor cells, which were negative for CD117 and CD34 and positive for Discovered on GIST-1 (DOG1). C-kit-negative GISTs could be treated by complete resection and/or imatinib, which is the same treatment for c-kit-positive GISTs.