Differentiation of ovarian serous carcinoma from ovarian clear cell carcinoma using a 10-gene signature selected by comprehensive gene expression analysis.

AIM: Ovarian serous carcinoma (OSC) and ovarian clear cell carcinoma (OCCC) are two major histological types of epithelial ovarian carcinoma (EOC), each with different biological features and clinical behaviors. Although immunostaining is commonly used for differential diagnosis between OSC and OCCC, correct identification of EOC with mixed-type histology is sometimes a diagnostic challenge. The aim of the present study was to explore candidate genes as potential diagnostic biomarkers that distinguish OSC from OCCC. METHODS: A total of 57 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery. Total RNAs were extracted from fresh-frozen tissues of EOC patients, and were used for comprehensive gene expression analysis using DNA microarray technology. RESULTS: Ten candidate genes, FXYD2, TMEM101, GABARAPL1, ARG2, GLRX, RBPMS, GDF15, PPP1R3B, TOB1, and GSTM3 were up-regulated in OCCC compared to OSC. All EOC patients were divided into two groups according to hierarchical clustering using a 10-gene signature. CONCLUSION: Our data suggest that the 10 candidate genes would be an excellent marker for distinguishing OSC from OCCC. Furthermore, the molecular signatures of the 10 genes may enlighten us on the differences in carcinogenesis, and provide a theoretical basis for OCCC's resistance to chemotherapy in the future.

Evaluation of semitendinosus muscle transposition for treatment of perineal hernias in 33 small-breed dogs.

Little is known about the perioperative complications and treatment outcomes of repairing perineal hernias using semitendinosus muscle transposition (SMT) in small-breed dogs. The objective of this study was to retrospectively evaluate the complications and prognosis of perineal hernia repair using SMT in 33 small, male dogs (weighing < 15 kg). Before the study began, the medical records of all small-breed dogs that underwent SMT from March 2013 to June 2022 at the Veterinary Medical Center, University of Tokyo were analyzed, and telephone interviews were conducted with their owners or referring physicians. Short-term complications were observed in 42.4% of the patients. Lameness was the most common complication, although all cases were resolved within a few days. The recurrence rate during the study period (median: 265 d) was 9.1%. The results of this study showed that transposition of the semitendinosus muscle is more invasive than other surgical procedures for perineal hernias. It is, however, an effective alternative when repair with internal obturator muscle transposition alone is expected to be difficult, such as severe atrophy of the internal obturator muscle or herniation in the ventral direction, and in cases with a history of surgery by transposition of the internal obturator muscle.

On sait peu de choses sur les complications peropératoires et les résultats du traitement de la réparation des hernies périnéales à l'aide de la transposition du muscle semi-tendineux (SMT) chez les chiens de petite race. L'objectif de cette étude était d'évaluer rétrospectivement les complications et le pronostic de la réparation d'une hernie périnéale par SMT chez 33 petits chiens mâles (pesant < 15 kg). Avant le début de l'étude, les dossiers médicaux de tous les chiens de petite race ayant subi une SMT de mars 2013 à juin 2022 au Veterinary Medical Center de l'Université de Tokyo ont été analysés et des entrevues téléphoniques ont été menées avec leurs propriétaires ou médecins vétérinaires référents. Des complications à court terme ont été observées chez 42,4 % des patients. La boiterie était la complication la plus courante, bien que tous les cas aient été résolus en quelques jours. Le taux de récidive au cours de la période d'étude (médiane: 265 jours) était de 9,1 %. Les résultats de cette étude ont démontré que la transposition du muscle semi-tendineux est plus invasive que les autres interventions chirurgicales pour les hernies périnéales. Il s'agit cependant d'une alternative efficace lorsque la réparation par transposition du muscle obturateur interne seul s'annonce difficile, comme une atrophie sévère du muscle obturateur interne ou une hernie dans le sens ventral, et dans les cas d'antécédents chirurgicaux par transposition du muscle obturateur interne.(Traduit par Docteur Serge Messier).

Impaired Repopulating Ability of Uhrf2-/- Hematopoietic Progenitor Cells in Mice.

UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated Uhrf2-/- mice to clarify the role of UHRF2 deletion in hematopoiesis. Compared to Uhrf2+/+ mice, Uhrf2-/- mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between Uhrf2+/+ mice and Uhrf2-/- mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of Uhrf2-/- cells were decreased relative to Uhrf2+/+ cells in all lineages. After the second BMT, Uhrf2-/- neutrophils were few, while 20-30% of Uhrf2-/- T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in Uhrf2-/- hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in Uhrf2-/- HSPCs in a cleavage under targets and tagmentation assay. While UHRF2 deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that UHRF2 may play a role in the regulation of hematopoiesis.

Brain-specific glycosylation enzyme GnT-IX maintains levels of protein tyrosine phosphatase receptor PTPRZ, thereby mediating glioma growth.

Gliomas are the most prevalent primary tumor of the central nervous system. Despite advances in imaging technologies, neurosurgical techniques, and radiotherapy, a cure for high-grade glioma remains elusive. Several groups have reported that protein tyrosine phosphatase receptor type Z (PTPRZ) is highly expressed in glioblastoma, and that targeting PTPRZ attenuates tumor growth in mice. PTPRZ is modified with diverse glycan, including the PTPRZ-unique human natural killer-1 capped O-mannosyl core M2 glycans. However, the regulation and function of these unique glycans are unclear. Using CRISPR genome-editing technology, we first demonstrated that disruption of the PTPRZ gene in human glioma LN-229 cells resulted in profoundly reduced tumor growth in xenografted mice, confirming the potential of PTPRZ as a therapeutic target for glioma. Furthermore, multiple glycan analyses revealed that PTPRZ derived from glioma patients and from xenografted glioma expressed abundant levels of human natural killer-1-capped O-Man glycans via extrinsic signals. Finally, since deficiency of O-Man core M2 branching enzyme N-acetylglucosaminyltransferase IX (GnT-IX) was reported to reduce PTPRZ protein levels, we disrupted the GnT-IX gene in LN-229 cells and found a significant reduction of glioma growth both in vitro and in the xenograft model. These results suggest that the PTPR glycosylation enzyme GnT-IX may represent a promising therapeutic target for glioma.

Podoplanin promotes cell proliferation, survival, and migration of canine non-tonsillar squamous cell carcinoma.

Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.

Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma.

Mucosal melanoma metastasizes at an early stage of the disease in human and dog. We revealed that overexpression of podoplanin in tumor invasion fronts (IF) was related to poor prognosis of dogs with mucosal melanoma. Moreover, podoplanin expressed in canine mucosal melanoma cells promotes proliferation and aggressive amoeboid invasion by activating Rho-associated kinase (ROCK)-myosin light chain 2 (MLC2) signaling. PDPN-ROCK-MLC2 signaling plays a role in cell-cycle arrest and cellular senescence escape as a mechanism for regulating proliferation. Podoplanin induces amoeboid invasion in the IFs of mouse xenografted tumor tissues, similar to canine mucosal melanoma clinical samples. We further identified that podoplanin expression was related to poor prognosis of human patients with mucosal melanoma, and human mucosal melanoma with podoplanin-high expression enriched gene signatures related to amoeboid invasion, similar to canine mucosal melanoma. Overall, we propose that podoplanin promotes canine and human mucosal melanoma metastasis by inducing aggressive amoeboid invasion and naturally occurring canine mucosal melanoma can be a novel research model for podoplanin expressing human mucosal melanoma. IMPLICATIONS: Podoplanin could be a new therapeutic target to restrict the metastatic dissemination of canine and human mucosal melanoma.

Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

High-grade B-cell lymphoma with 11q aberrations: A single-center study.

High-grade B-cell lymphoma with 11q aberrations (HGBL-11q) has been classified for the first time as a high-grade mature B-cell neoplasm according to the 5th edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. HGBL-11q is morphologically and immunohistochemically similar to Burkitt lymphoma (BL) or HGBL; it is characterized by gain in the 11q23.2-11q23.3 region and loss in the 11q24.1-qter region but it lacks MYC translocation. HGBL-11q is a rare tumor, and its exact frequency in Japan remains unclear. In this study, we classified 113 Germinal center B-cell (GCB) type aggressive B-cell lymphomas (BCLs), which were divided into BL, high-grade (HG), and large cell (LC) morphologies. We performed fluorescence in situ hybridization (FISH) to identify 11q aberrations. Nine patients had 11q aberrations (7.96%, 9/113), including six HGBL-11q. The age range was from 8 to 87 years, and all were male. Six out of 14 patients with HG morphology were diagnosed with HGBL-11q (6/14, 42.9%). HGBL-11q has been found to occur primarily in children and young adults but also in middle-aged and older adults. Patients with HG morphology without MYC translocation should undergo FISH for 11q aberrations regardless of age. However, the pathogenesis, clinical findings, and prognosis of HGBL-11q remain unclear. The accumulation of cases with an accurate HGBL-11q diagnosis in daily practice and accurate and detailed data on HGBL-11q will contribute to further understanding of 11q aberrations.

SPON1 is an independent prognostic biomarker for ovarian cancer.

BACKGROUND: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. METHODS: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. RESULTS: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. CONCLUSIONS: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

Claudin-4-adhesion signaling drives breast cancer metabolism and progression via liver X receptor ß.

BACKGROUND: Cell adhesion is indispensable for appropriate tissue architecture and function in multicellular organisms. Besides maintaining tissue integrity, cell adhesion molecules, including tight-junction proteins claudins (CLDNs), exhibit the signaling abilities to control a variety of physiological and pathological processes. However, it is still fragmentary how cell adhesion signaling accesses the nucleus and regulates gene expression. METHODS: By generating a number of knockout and rescued human breast cell lines and comparing their phenotypes, we determined whether and how CLDN4 affected breast cancer progression in vitro and in vivo. We also identified by RNA sequencing downstream genes whose expression was altered by CLDN4-adhesion signaling. Additionally, we analyzed by RT-qPCR the CLDN4-regulating genes by using a series of knockout and add-back cell lines. Moreover, by immunohistochemistry and semi-quantification, we verified the clinicopathological significance of CLDN4 and the nuclear receptor LXRß (liver X receptor ß) expression in breast cancer tissues from 187 patients. RESULTS: We uncovered that the CLDN4-adhesion signaling accelerated breast cancer metabolism and progression via LXRß. The second extracellular domain and the carboxy-terminal Y197 of CLDN4 were required to activate Src-family kinases (SFKs) and the downstream AKT in breast cancer cells to promote their proliferation. Knockout and rescue experiments revealed that the CLDN4 signaling targets the AKT phosphorylation site S432 in LXRß, leading to enhanced cell proliferation, migration, and tumor growth, as well as cholesterol homeostasis and fatty acid metabolism, in breast cancer cells. In addition, RT-qPCR analysis showed the CLDN4-regulated genes are classified into at least six groups according to distinct LXRß- and LXRßS432-dependence. Furthermore, among triple-negative breast cancer subjects, the "CLDN4-high/LXRß-high" and "CLDN4-low and/or LXRß-low" groups appeared to exhibit poor outcomes and relatively favorable prognoses, respectively. CONCLUSIONS: The identification of this machinery highlights a link between cell adhesion and transcription factor signalings to promote metabolic and progressive processes of malignant tumors and possibly to coordinate diverse physiological and pathological events.

Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren's syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders.

The sequential progression from chronic liver disease to cirrhosis may be a risk factor for hepatocellular carcinoma (HCC) development. Although HCC originates from hepatitis B virus- or hepatitis C virus-associated liver cirrhosis, it has recently been reported in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis. However, little is known about the pathophysiological mechanisms linking HCC to rheumatic disorders, including rheumatoid arthritis (RA). Herein, we describe the case of HCC with NASH complicated by RA and Sjögren's syndrome (SS). A fifty-two-year-old patient with RA and diabetes was referred to our hospital for further examination of a liver tumor. She received methotrexate (4 mg/week) for 3 years and adalimumab (40 mg/biweekly) for 2 years. On admission, laboratory data showed mild thrombocytopenia and hypoalbuminemia, with normal hepatitis virus markers or liver enzymes. Anti-nuclear antibodies were positive with high titers (x640), and anti-SS-A/Ro (187.0 U/ml; normal range [NR]: ≤6.9 U/mL) and anti-SS-B/La (320 U/ml; NR: ≤6.9 U/mL) antibodies were also high. Abdominal ultrasonography and computed tomography revealed liver cirrhosis and a tumor in the left lobe (S4) of the liver. She was diagnosed with HCC based on imaging findings, and elevated levels of protein induced by vitamin K absence- II (PIVKA-II) were detected. She underwent laparoscopic partial hepatectomy, and histopathological examination revealed steatohepatitis HCC with background liver cirrhosis. The patient was discharged on the 8th day post-operation without any complications. At the 30 months follow-up, no significant evidence of recurrence was observed. Our case suggests that clinical screening for HCC is needed in patients with RA who are at a high risk of NASH, as they may progress to HCC even without elevated liver enzymes.

Different prognostic outcomes in two cases of FDG-PET/CT-Positive and -negative cardiac angiosarcoma.

Cardiac angiosarcoma is a rare malignant tumor with a poor prognosis, characterized by the high uptake of 18F-fluorodeoxyglucose (FDG). This case report presents two cases of cardiac angiosarcoma with a marked difference in FDG uptake and prognosis.Case Summary:Case 1: A 40-year-old male presented with syncope. Ultrasound echocardiography demonstrated a cardiac tumor with a high uptake of 18F-FDG (maximum standardized uptake value=9.2). The patient underwent heart catheterization and tumor biopsy. The pathological result was high-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was approximately 20%. Systemic chemotherapy was administered; however, the patient died 2 years and 5 months after disease onset.Case 2: A 65-year-old female had a right atrial tumor incidentally diagnosed during routine ultrasound echocardiography. The tumor exhibited a low uptake of 18F-FDG (maximum standardized uptake value=1.8). Open heart surgery was performed, and the tumor was completely resected. Histological analysis revealed low-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was less than 5%. The patient was followed-up and had not relapsed 2 years after surgery.Conclusion: 18F-FDG uptake may reflect pathological tumor grade and prognosis in cardiac angiosarcoma.

Rapid Clinical Improvement of Multicentric Castleman Disease (MCD) with Renal Involvement Following Treatment with Tocilizumab: AA Amyloidosis as a Possible Renal Involvement of MCD.

Castleman disease (CD) is a lymphoproliferative disorder that manifests as hypergammaglobulinemia and severe inflammation with multiorgan involvement. However, renal involvement has been infrequently described in CD. We present a case of a 63-year-old Japanese male patient with multicentric CD (MCD) in whom kidney involvement, including impaired renal function and massive proteinuria, is present. He had a 2-year history of inflammatory arthritis and was referred to our clinic with newly developed proteinuria, renal dysfunction, and elevated levels of acute-phase proteins. Abdominal computed tomography scan revealed hepatosplenomegaly, including mesenteric and inguinal lymph node enlargements. The patient underwent inguinal lymph node resection. Excisional biopsy of the inguinal lymph node showed multiple lymphoid follicles and expansion of interfollicular areas by marked plasmacytosis consistent with mixed type CD. The patient was diagnosed with human herpes virus 8-negative MCD according to the international diagnostic criteria for CD. Diagnostic renal biopsy was not performed following the medical viewpoint. Tocilizumab (TCZ) treatment was highly effective in reducing proteinuria and stabilizing renal function, as well as improving other clinical symptoms. The patient responded to TCZ treatment, and the renal involvement was rapidly improved. Our preliminary immunohistochemical analysis indicated AA amyloid deposits in urinary epithelial cells suggesting a possible renal involvement of AA amyloidosis. TCZ could potentially be one of the therapeutic options in patients with MCD with renal involvement.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Acquired von Willebrand Syndrome in a Patient with Multiple Comorbidities, Including MALT Lymphoma with IgA Monoclonal Gammopathy and Hyperviscosity Syndrome.

Acquired von Willebrand syndrome (aVWS) develops with various underlying diseases. We herein report an individual with aVWS associated with mucosa-associated lymphoid tissue lymphoma in the lungs complicated by hyperviscosity syndrome, Sjögren's syndrome, and hypothyroidism. This patient developed life-threatening hemorrhaging during a lung biopsy despite transfusion of concentrate of plasma-derived VWF/factor VIII. The use of rituximab caused remission of the lymphoma and hyperviscosity syndrome in parallel with the resolution of aVWS. Thus, lymphoma and hyperviscosity might result in aVWS. Invasive procedures with a risk of bleeding should be avoided in individuals with aVWS.

Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in the Remnant Stomach.

Endoscopic submucosal dissection (ESD) in patients with early gastric cancers (EGCs) in the remnant stomach is technically difficult, owing to the limited space and fibrosis under the suture lines and anastomoses. Conversely, ESD for patients with EGCs in the remnant stomach is less invasive and provides better quality of life than completion total gastrectomy. To clarify the effectiveness and safety of ESD, we reviewed the medical records of patients with EGCs in the remnant stomach who underwent ESD between July 2006 and October 2020 at our institution. All identified patients were included in the analysis. Of 25 patients with 27 lesions, the en bloc and R0 resection rates were 88.9% and 85.2%, respectively. Neither perforation nor postoperative bleeding was observed. During a median follow-up period of 48 (range, 5-162) months, the 5-year overall survival rate was 71.0%, whereas the 5-year cause-specific survival rate was 100%. No obvious differences in the outcomes of procedures with suture line involvement and without suture line or anastomosis involvement were noted. In conclusion, ESD was effective and safe in patients with EGCs in the remnant stomach despite the suture line involvement.

Association between Submucosal Fibrosis and Endoscopic Submucosal Dissection of Recurrent Esophageal Squamous Cell Cancers after Chemoradiotherapy.

Endoscopic resection is a treatment of choice for a metachronous early-stage esophageal squamous cell carcinoma (ESCC) appearing after a radical cure of esophageal cancer by chemoradiotherapy (CRT). However, non-curative resection, and procedural complications including perforation due to radiation-induced submucosal fibrosis, are a concern. This study aimed to evaluate the association between submucosal fibrosis and the usefulness and safety of endoscopic submucosal dissection (ESD) in ESCC after CRT. This study retrospectively analyzed 13 lesions in 11 patients in our institute. Submucosal fibrosis under the lesion (F score) was classified into three levels (F0: none or mild, F1: moderate, and F2: severe) based on endoscopic and histopathologic findings. All lesions were F1 or greater (F1: 8 lesions and F2: 5 lesions). En bloc and R0 resection rates were both 100%. The procedural speed was slower in F2 than in F1 (F1 vs. F2; 15.1 mm2/min vs. 7.1 mm2/min, p = 0.019), without procedure-related adverse events. At a median follow-up of 42 months (range: 14-117 months) after ESD, 7 of 11 (63.6%) patients were alive without recurrence, and without ESCC-related death. ESCC after CRT reliably and safely resected en bloc by ESD but was more difficult in lesions with strong submucosal fibrosis.

Screening for hilar biliary invasion in ampullary cancer patients.

BACKGROUND: The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy. However, effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified. AIM: To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer. METHODS: Among 43 ampullary cancer patients, 34 underwent endoscopic treatment (n = 9) or surgery (n = 25). The use of imaging findings (thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography, irregularity on endoscopic retrograde cholangiography, thickening of the entire bile duct wall on intraductal ultrasonography (IDUS), and partial thickening of the bile duct wall on IDUS) and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared. RESULTS: Hilar invasion was not observed in every patient. Among the patients who did not undergo biliary stent insertion, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy (100%) for diagnosing hilar biliary invasion. However, each imaging method and biliary biopsy yielded some false-positive results. CONCLUSION: Although some false-positive results were obtained with each method, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer. However, hilar invasion of ampullary cancer is rare; therefore, the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.