BACKGROUND:Mapping biopsy (MB) can evaluate superficial ductal spread (SDS) through the histopathological diagnosis of cholangiocarcinoma, enabling the selection of an appropriate surgical procedure. This retrospective study evaluated the efficacy of MB using a novel sheath system in distal cholangiocarcinoma (dCCA) cases. METHODS:A total of 199 cholangiocarcinoma cases underwent preoperative diagnosis. Among them, 40, 21, and 26 cases underwent direct, sheath, and peroral cholangioscopy (POCS) MB, respectively, for dCCA. Each group was compared regarding their technical success rate and the diagnostic accuracy for SDS. RESULTS:Although all cases achieved technical success, the median procedure time of POCS (48-min) tended to be longer than direct (33-min) and sheath MB (30-min) (p overall = .092). Diagnostic specificity and accuracy were significantly higher in the sheath group (95.2%, 95.2%) compared to the direct (71.0%, 70.0%) and POCS (60.9%, 57.7%) MB groups (p overall = .019 and .0094). Multivariate analysis revealed that the sheath MB group was an independent significant factor for the accurate margin diagnosis (OR 0.11; 95% CI: 0.01-0.86, p = .0358). CONCLUSIONS:The sheath MB method provided the most accurate histopathological diagnosis of SDS in dCCA. To obtain a larger tissue sample and avoid tumor cell contamination, sheath MB is worth performing to assess the accuracy of the preoperative SDS diagnosis.

Streptozotocin (STZ) is known to induce renal tumors in rodents, but their similarity to human tumors remains poorly defined. We characterized and comparatively validated a mouse model of STZ-induced renal tumorigenesis by administering a single intraperitoneal dose of STZ (250 mg/kg) to female CBA/NSlc mice and maintaining them for 182 days. Renal tumors developed in 25 of 28 surviving mice (89%), with mean and median numbers of 3.4 and 2.5 tumors per animal, respectively. Histopathologically, the tumors were diagnosed as adenomas or adenocarcinomas and exhibited clear, eosinophilic, or mixed cytoplasm. Immunohistochemical analysis of four representative adenocarcinomas revealed positivity for CK AE1/AE3, CK7, PAX8, CD10, CD82, E-cadherin, CD117, and S100A1, and negativity for CK20 and vimentin. These morphological and immunohistochemical features resembled those of human chromophobe renal cell carcinoma (chRCC). Furthermore, the tumors expressed collecting duct markers (uromodulin, CD15, MUC1, and GLUT-1) but lacked proximal convoluted tubule markers (AQP1 and megalin), suggesting a collecting duct origin. Taken together, STZ-induced mouse renal tumors closely resemble human chRCC, providing a reproducible model for investigating the biology and potential therapeutic approaches for this tumor type.

Background: Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. Methods: l-carnitine (2 g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Results: Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Conclusions: Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

Pseudomyxoma peritonei (PMP) is a rare disease caused by primary mucinous neoplasms. Here, we describe a case where a large ovarian tumor was initially removed laparoscopically, followed by an appendectomy. The patient was diagnosed with PMP arising from an ovarian mucinous borderline tumor with a KRAS mutation. Treatment included bevacizumab-containing chemotherapy, resulting in complete remission.

A 59-year-old man receiving sunitinib chemotherapy for postoperative recurrence of renal cell carcinoma (RCC) metastases was found to have multiple metastases on contrast-enhanced computed tomography (CECT). CECT revealed a typical hyperdense enhanced nodule in the arterial phase of the stomach and head and tail of the pancreas. However, in the uncinate process of the pancreas, CECT revealed an atypical image and a hypodense enhanced nodule in each phase. Both lesions were finally pathologically diagnosed as clear cell carcinoma. Treatment-modified pancreatic metastases from RCC may present with nonspecific images; therefore, caution is required when deciding on treatment strategies.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML). Methods: Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles.Results: Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/ histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding adverse events (AEs) were observed in three patients in the Franseen group.Conclusions: Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Malignant melanoma (MM) is a tumor that usually occurs in the skin, but this malignant tumor can also develop in extracutaneous tissues, including urogenital tissues. In regard to MM occurring in urogenital tissues, bladder origin is common but renal primary MM is extremely rare. In the Department of Emergency and Urology at Gifu Municipal Hospital, a tumor of the right kidney was detected in a computed tomography scan to determine the cause of severe pain in the lower extremities of a 45-year-old Japanese woman. With the clinical diagnosis of renal cell carcinoma, resection of the right kidney was performed under laparoscopy. The cut surface of the tumor encapsulated by a thick fibrous capsule was dark brown, and the tumor cells with large nuclei, large nucleoli, acidophil cytoplasm, and numerous melanin granules showed papillary, solid, or alveolar growth. Immunohistochemically, the tumor cells were positive for Melan A and human melanoma black 45 (HMG45) but negative for transcription factor E3 (TFE3), transcription factor EB (TFEB), cytokeratin 7 (CK7), carbonic anhydrase 9 (CA9), and AEl/AE3. We conducted careful and detailed examinations, including an association of the patient's medical history, but there were no indications for tumors, particularly MM, in any organs. Therefore, she was ultimately diagnosed with primary kidney MM.

BACKGROUND AND AIMS:Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease. METHODS:This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB. RESULT:An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry. CONCLUSION:The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment.

Warthin's tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin's tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin's tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin's tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin's tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin's tumor with possible involvement of IgG4-related sialadenitis.

Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland, mostly in the parotid gland. The epithelial cells constituting a tumor are characterized by the presence of mitochondria that undergo structural and functional changes, resulting in the development of oncocytes. In addition to containing epithelial cells, Warthin’s tumors contain abundant lymphocytes with lymph follicles (germinal centers) that are surrounded by epithelial cells. The pathogenesis of Warthin’s tumor is not fully understood, and several hypotheses have been proposed. The risk factors for the development of Warthin’s tumor, which predominantly occurs in males, include aging, smoking, and radiation exposure. Recently, it has been reported that chronic inflammation and aging cells promote the growth of Warthin’s tumor. Several reports regarding the origin of the tumor have suggested that (1) Warthin’s tumor is an IgG4-related disease, (2) epithelial cells that compose Warthin’s tumor accumulate mitochondria, and (3) Warthin’s tumor is a metaplastic lesion in the lymph nodes. It is possible that the pathogenesis of Warthin’s tumor includes mitochondrial metabolic abnormalities, accumulation of aged cells, chronic inflammation, and senescence-associated secretory phenotype (SASP). In this short review, we propose that DNA damage, metabolic dysfunction of mitochondria, senescent cells, SASP, human papillomavirus, and IgG4 may be involved in the development of Warthin’s tumor.

The Journal of DermatologyEarly View LETTER TO THE EDITOR A case of gas gangrene caused by Clostridium septicum with undiagnosed advanced colon cancer Anna Sumigama, Anna Sumigama orcid.org/0009-0001-8453-1057 Department of Dermatology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorYusuke Goto, Yusuke Goto Department of Dermatology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorYoshiyuki Ohno, Yoshiyuki Ohno Department of Orthopedic Surgery, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorHiroto Ohata, Hiroto Ohata Department of Anesthesiology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorMitsuru Okuno, Mitsuru Okuno Department of Gastroenterology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorAkane Onogi, Akane Onogi Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorNaoki Watanabe, Naoki Watanabe Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorTakuji Tanaka, Takuji Tanaka orcid.org/0000-0002-1428-1582 Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorHiroyuki Kanoh, Corresponding Author Hiroyuki Kanoh [email protected] orcid.org/0000-0002-1774-8600 Department of Dermatology, Gifu Municipal Hospital, Gifu, Japan Correspondence Hiroyuki Kanoh, Department of Dermatology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, Japan. Email: [email protected]Search for more papers by this author Anna Sumigama, Anna Sumigama orcid.org/0009-0001-8453-1057 Department of Dermatology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorYusuke Goto, Yusuke Goto Department of Dermatology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorYoshiyuki Ohno, Yoshiyuki Ohno Department of Orthopedic Surgery, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorHiroto Ohata, Hiroto Ohata Department of Anesthesiology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorMitsuru Okuno, Mitsuru Okuno Department of Gastroenterology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorAkane Onogi, Akane Onogi Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorNaoki Watanabe, Naoki Watanabe Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorTakuji Tanaka, Takuji Tanaka orcid.org/0000-0002-1428-1582 Department of Pathology, Gifu Municipal Hospital, Gifu, JapanSearch for more papers by this authorHiroyuki Kanoh, Corresponding Author Hiroyuki Kanoh [email protected] orcid.org/0000-0002-1774-8600 Department of Dermatology, Gifu Municipal Hospital, Gifu, Japan Correspondence Hiroyuki Kanoh, Department of Dermatology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, Japan. Email: [email protected]Search for more papers by this author First published: 03 March 2024 https://doi.org/10.1111/1346-8138.17167Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (laboratory risk indicator for necrotizing fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004; 32: 1535–1541. 10.1097/01.CCM.0000129486.35458.7D PubMedWeb of Science®Google Scholar 2Kiel N, Ho V, Pascoe A. A case of gas gangrene in an immunosuppressed Crohn's patient. World J Gastroenterol. 2011; 17: 3856–3858. 10.3748/wjg.v17.i33.3856 CASPubMedWeb of Science®Google Scholar 3Stevens DL, Musher DM, Watson DA, Eddy H, Hamill RJ, Gyorkey F, et al. Spontaneous, nontraumatic gangrene due to Clostridium septicum. Rev Infect Dis. 1990; 12: 286–296. 10.1093/clinids/12.2.286 CASPubMedWeb of Science®Google Scholar 4Alpern RJ, Dowell VR. Clostridium septicum infections and malignancy. JAMA. 1969; 209: 385–388. 10.1001/jama.1969.03160160021004 CASPubMedWeb of Science®Google Scholar 5Koransky JR, Stargel MD, Dowell VR Jr. Clostridium septicum bacteremia. Its clinical significance. Am J Med. 1979; 66: 63–66. 10.1016/0002-9343(79)90483-2 CASPubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

The identification of anticancer therapies using next-generation sequencing (NGS) is necessary for the treatment of cholangiocarcinoma. NGS can be easily performed when cell blocks (CB) are obtained from bile stored overnight. We compared NGS results of paired CB and surgically resected specimens (SRS) from the same cholangiocarcinoma cases. Of the prospectively collected 64 bile CBs from 2018 to 2023, NGS was performed for three cases of cholangiocarcinoma that could be compared with the SRS results. The median numbers of DNA and RNA reads were 95,077,806 [CB] vs. 93,161,788 [SRS] and 22,101,328 [CB] vs. 24,806,180 [SRS], respectively. We evaluated 588 genes and found that almost all genetic alterations were attributed to single-nucleotide variants, insertions/deletions, and multi-nucleotide variants. The coverage rate of variants in SRS by those found in CB was 97.9–99.2%, and the coverage rate of SRS genes by CB genes was 99.6–99.7%. The NGS results of CB fully covered the variants and genetic alterations observed in paired SRS samples. As bile CB is easy to prepare in general hospitals, our results suggest the potential use of bile CB as a novel method for NGS-based evaluation of cholangiocarcinoma.

PDF file - 507K, Heat map of serial gene expression profiling in liver of Pdgf-c Tg mice that developed hepatic fibrosis and tumors. Differentially expressed genes clustered in a one way hierarchical method among seven grouped samples: WT mice at 20 weeks and 48 weeks, non-tumor portion of Pdgf-c Tg mouse livers fed a basal diet at 20 weeks and 48 weeks, tumor portion (Hee) of Pdgf-c Tg mouse livers fed a basal diet at 48 weeks, non-tumor portion of Pdgf-c Tg mouse livers fed with 0.06% peretinoin at 20 weeks and 48 weeks. Three large clusters (A, B and e) were obtained. Representative gene names listed on right hand side.

PDF file - 133K, (A) Western blotting of PDGFR-o, POGFR-p, VEGFR2, p-AKT, p-ERK112 and GAPDH expression in Huh-7, HepG2, NH3T3, HLE, HUVEC and Lx-2 cells treated with peretinoin. (B) RTD-peR evaluation of collagen 1a2 in Lx-2, HLE and HUh-7 cells with or without peretinoin (20 IJM) (n=3). (C) Time course of PDGF-a, Sp1, c-Jun and p-c-Jun after peretinoin treatment in HUh-7 cells.