A case of strangulated bowel obstruction in which transabdominal ultrasound was useful for preoperative diagnosis.

A 74-year-old man presented to the emergency department with the chief complaint of abdominal pain. A computed tomography scan showed paralytic ileus. An ileostomy tube was placed, but the symptoms of bowel obstruction did not improve. Two days after admission, the patient's renal function deteriorated. Transabdominal ultrasound (TUS) showed linear high-intensity echoes consistent with a fibrotic band and microbubbles suggestive of circulatory disturbance in the dilated intestinal tract. Subsequent contrast-enhanced ultrasound revealed circulatory disturbance of the small bowel wall. Emergency surgery was performed under the diagnosis of strangulated ileus. Intraoperative examination revealed that the terminal ileum was strangulated by a fibrotic band from the retroperitoneum, which was confirmed by TUS. The fibrotic band was resected, the strangulation was released, and ileocecal resection was performed. Postoperatively, intestinal peristalsis was rapidly restored. TUS was able to depict the fibrotic band, which could not be detected by a computed tomography scan, allowing the patient to undergo immediate surgical treatment. We herein report this case of strangulated bowel obstruction in which TUS and contrast-enhanced ultrasound were useful in preoperative assessment of the patient's condition.

Appendiceal mucocele pathologically classified as appendiceal epithelial hyperplasia and preoperatively diagnosed by contrast-enhanced ultrasonography: A case report.

We report a patient with a mucocele with diffuse wall thickening diagnosed by transabdominal ultrasonography and contrast-enhanced ultrasonography. Transabdominal ultrasonography showed diffuse thickening of the entire appendix wall and an anechoic area that appeared to be fluid collected throughout the appendix lumen. However, the "onion skin sign" was not detected. Contrast-enhanced ultrasonography combined with superb microvascular imaging revealed abundant mucosal blood flow and no abnormal vascular network within the mucosa of the appendix wall. We preoperatively diagnosed a mucocele complicated by acute and chronic appendicitis, and ileocecal resection was performed. Macroscopic and microscopic findings of the resected specimens demonstrated that the appendiceal wall was diffusely thickened, with fibrosis and inflammatory cell infiltration, and that the appendiceal root rumen was narrowed with epithelial hyperplasia. No neoplastic changes were observed. The cause of the appendiceal mucocele was likely fibrosis and stenosis at the root of the appendix due to initial acute appendicitis.

Benefit of Continuation of Low-Dose Imatinib for Gastrointestinal Stromal Tumors despite Adverse Events with Regular-Dose Imatinib.

Tyrosine kinase inhibitors (TKIs) such as imatinib improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). However, treatment options for GISTs are still limited, and the continuation of TKIs is difficult due to adverse events in some cases. The effectiveness of low-dose imatinib is unclear. We report 2 cases to show effectiveness of low-dose imatinib in patients with adverse events. The first case is a male in his early 60s with a history of intestinal GIST resection who was diagnosed with recurrent GIST with peritoneal dissemination. He was started on low-dose imatinib (300 mg) because of a history of subconjunctival hemorrhage after receiving postoperative imatinib. Follow-up contrast-enhanced ultrasonography revealed that the tumors had shrunk in size and number after 2 months of treatment with 300-mg imatinib. He continued this treatment and showed partial response for 8 months. The second case is a female in her late 70s with rectal GIST who was treated with imatinib 400 mg. Due to a severe skin lesion, she changed her treatment to sunitinib 2 months after initiation. However, new metastasis in the liver was confirmed after 4 months of administration of sunitinib. She underwent surgical esection of the rectal tumor to reduce the volume. After the surgery, low-dose imatinib (300 mg) with oral steroids was adopted. Follow-up confirmed the absence of recurrence at the rectum and no increase in hepatic tumor size for 18 months. Aggressive treatment with low-dose imatinib instead of discontinuation or alteration of treatment may benefit patients with unresectable and postoperative GISTs with sensible mutation to imatinib.

Ectopic PTH-producing parathyroid cyst inside the thymus: a case report.

BACKGROUND: The hallmark of hyperparathyroidism is hypersecretion of parathyroid hormone (PTH) which results in hypercalcemia and hypophosphatemia. While hypercalcemia due to malignancy is often brought about by PTH-related protein in adults, PTH-producing tumors are quite rare in clinical practice. Additionally, from the point of embryology, it is very difficult to examine ectopic PTH-producing tissue such as ectopic parathyroid glands. Furthermore, clear histopathological criteria are not present. CASE PRESENTATION: A 57-year-old woman was referred to our hospital for hypercalcemia. Her parathyroid hormone (PTH) level was elevated, but there were no enlarged parathyroid glands. Although 99mTc-MIBI confirmed a localized and slightly hyperfunctioning parathyroid tissue in the anterior mediastinum, it was not typical as hyperfunctioning parathyroid. We finally diagnosed her as ectopic PTH-producing cyst-like tumor with venous sampling of PTH. She underwent anterosuperior mediastinal ectopic PTH-producing cyst-like tumor resection. It is noted that intact-PTH concentration of the fluid in the cyst was very high (19,960,000 pg/mL). Based on histopathological findings, we finally diagnosed her as ectopic PTH-producing parathyroid cyst inside the thymus. After resection of anterosuperior mediastinal thymus including ectopic PTH-producing parathyroid cyst, calcium and intact-PTH levels were decreased, and this patient was discharged without any sequelae. CONCLUSIONS: We should know the possibility of superior mediastinal ectopic PTH-producing parathyroid cyst inside the thymus among subjects with ectopic PTH-producing parathyroid glands. Particularly when the cyst is present in the superior mediastinum, it is necessary to do careful diagnosis based on not only positive but also negative findings in 99mTc-MIBI. It is noted that the patient's bloody fluid in the cyst contained 19,960,000 pg/mL of intact-PTH, and its overflow into blood stream resulted in hyperparathyroidism and hypercalcemia. Moreover, in such cases, the diagnosis is usually confirmed after through histological examination of ectopic PTH-producing parathyroid glands. We think that it is very meaningful to let clinicians know this case.

Inhibition of pancreatic cancer-cell growth and metastasis in vivo by a pyrazole compound characterized as a cell-migration inhibitor by an in vitro chemotaxis assay.

Pancreatic cancer is recalcitrant to treatment as it is highly metastatic and rapidly progressive. While observing the behavior of human pancreatic BxPC-3 cells using an optical assay device called TAXIScan, we found that several synthetic pyrazole and pyrimidine derivatives inhibited cell migration. One such compound, 14-100, inhibited metastasis of fluorescence-labeled BxPC-3 cells, which were transplanted into the pancreas of nude mice as a subcutaneously grown cancer fragment. Surprisingly, despite its low cytotoxicity, the compound also showed an inhibitory effect on cancer cell proliferation in vivo, suggesting that the compound alters cancer cell characteristics needed to grow in situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound 14-100 could be a good drug candidate against pancreatic cancer.

[A case of CA19-9-producing esophagogastric junction cancer with ovarian juvenile granulosa cell tumor and rectal cancer].

This is a report on a case of CA19-9-producing cancer of esophagogastric junction with rectal cancer and a suspicion of Krukenberg tumor, a metastasized ovarian tumor that would mean an inoperable condition of cancer progression if that were true. This was a case of a woman in her 60s who was diagnosed with double cancers at the esophagogastric junction and rectum with a swollen left ovary. She had a laparoscopic bilateral salpingo-oophorectomy to get a histologic diagnosis, which should affect the subsequent therapeutic strategy because metastasis to the ovary meant an inoperable cancer progression. The resected ovary was diagnosed as juvenile granulosa cell tumor, but not Krukenberg tumor. Thus, subsequent curative surgeries, such as thoracolaparotomy for esophagogastric junction cancer and robot-assisted surgery for rectal cancer, were performed. Immunohistochemical examination revealed that the expression of CA19-9 was strongly observed in the tumor of esophagogastric junction, but not in the tumors of rectum or ovary. Furthermore, serum CA19-9 was drastically decreased after the resection of esophagogastric junction cancer. In aggregate, this esophagogastric junction cancer met the criteria of CA19-9-producing gastric cancer defined by Okinaga et al. So far, 46 cases of CA19-9-producing gastric cancer including this case have been reported in Japanese literature. Interestingly, this case had another characteristic of juvenile granulosa cell tumor, one of borderline malignant sex cord-stromal tumors rarely found in adults.

Asymptomatic gangrenous cholecystitis diagnosed using contrast-enhanced ultrasonography in a patient with pancreatic cancer.

A 72-year-old female without abdominal symptoms visited our hospital for routine follow-up while undergoing pancreatic cancer treatment (using TS-1). Her vital signs were normal, and her abdomen was soft and non-tender. Blood test revealed elevated C-reactive protein levels with normal white blood cell count. Computed tomography was performed for follow-up of pancreatic cancer. Contrast-enhanced computed tomography showed partial discontinuity and irregular thickness of the gallbladder wall; however, a definitive diagnosis was not obtained due to unclear imaging. Contrast-enhanced transabdominal ultrasonography revealed intraluminal membranes in the gallbladder and a perfusion defect at the bottom, indicating gangrenous cholecystitis. Surgical resection was performed, and pathological examination showed severe necrosis of the gallbladder wall, consistent with the findings of contrast-enhanced transabdominal ultrasonography.

Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Diagnosis of Fibrotic Distal Ileum Stenosis after Ischemic Enteritis Using Transabdominal Ultrasonography.

Ischemic enteritis (IE) is a rare disorder which is caused by inadequate blood flow to small intestine. The diagnostic procedure of this disease has not sufficiently established because of its rarity. Here, we report a case of IE in a hemodialysis-dependent 70-year-old man and summarize the diagnostic options for IE. The patient was admitted to our hospital because of acute abdominal distention and vomiting. He presented with mild tenderness in the lower abdomen and slightly elevated C-reactive protein level as revealed by blood tests. Radiographic imaging showed small bowel obstruction due to a stricture in the distal ileum. Contrast-enhanced abdominal ultrasonography revealed a 7-cm stenotic site with increased intestinal wall thickening, which preserved mucosal blood perfusion. Elastography revealed a highly elastic alteration of the stenotic lesion, indicating benign fibrotic changes resulting from chronic insufficient blood flow. Based on a clinical diagnosis of IE with fibrous stenosis, a partial ileostomy was performed. After surgical treatment, oral intake was initiated without recurrence of intestinal obstruction. Pathological findings revealed deep ulceration with inflammatory cell infiltration at the stenotic site. Occlusion and hyalinization of the venules in the submucosal layer indicated IE. In addition to current case, we reviewed past case reports of IE. Through this case presentation and literature review, we summarize the usefulness and safety of transabdominal ultrasonography for diagnosing IE.

MRI and CT features of a malignant myoepithelioma of the scrotum: A case report and literature review.

Malignant myoepithelioma of the scrotum is extremely rare. We report the case of a 51-year-old man with malignant myoepithelioma of the scrotum, wherein computed tomography and magnetic resonance imaging revealed a lobulated soft tissue mass with calcification, cystic component, and solid component with gradual contrast enhancement on dynamic contrast-enhanced scans. The patient presented with scrotal induration, and there was no elevation of tumor markers and no evidence of a metastatic lesion on computed tomography and magnetic resonance imaging. Histopathological examination of the resected scrotal specimen confirmed a well-circumscribed solid tumor with septa, a small area of hemorrhage, and necrosis. The subsequent diagnosis was malignant myoepithelioma of the scrotum. This case shows that scrotal malignant myoepithelioma might appear as a well-defined lobulated mass with cystic regions. We conjecture that the enhancement pattern and apparent diffusion coefficient values can be potential markers for scrotal myoepithelial tumors.

Upregulation of Mobility in Pancreatic Cancer Cells by Secreted S100A11 Through Activation of Surrounding Fibroblasts.

S100A11, a member of the S100 family of proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in crosstalking between PDAC cells and surrounding fibroblasts in PDAC progression. An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation end products (RAGE) upon S100A11 binding and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinase kinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and its catalyzed production of prostaglandin E2 (PGE2), a strong chemoattractive fatty acid. The extracellularly released PGE2 from fibroblasts was required for the rise in cellular migration as well as infiltration of their adjacent PDAC cells in a coculture setting. Taken together, our data reveal a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway. The findings of this study will contribute to the establishment of a novel therapeutic antidote to PDACs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) through targeting the identified pathway.

Extracellular S100A11 Plays a Critical Role in Spread of the Fibroblast Population in Pancreatic Cancers.

The fertile stroma in pancreatic ductal adenocarcinomas (PDACs) has been suspected to greatly contribute to PDAC progression. Since the main cell constituents of the stroma are fibroblasts, there is crosstalking(s) between PDAC cells and surrounding fibroblasts in the stroma, which induces a fibroblast proliferation burst. We have reported that several malignant cancer cells including PDAC cells secrete a pronounced level of S100A11, which in turn stimulates proliferation of cancer cells via the receptor for advanced glycation end products (RAGE) in an autocrine manner. Owing to the RAGE+ expression in fibroblasts, the extracellular abundant S100A11 will affect adjacent fibroblasts. In this study, we investigated the significance of the paracrine axis of S100A11-RAGE in fibroblasts for their proliferation activity. In in vitro settings, extracellular S100A11 induced upregulation of fibroblast proliferation. Our mechanistic studies revealed that the induction is through RAGE-MyD88-mTOR-p70 S6 kinase upon S100A11 stimulation. The paracrine effect on fibroblasts is linked mainly to triggering growth but not cellular motility. Thus, the identified pathway might become a potential therapeutic target to suppress PDAC progression through preventing PDAC-associated fibroblast proliferation.

Histological evaluation of myeloproliferative neoplasms.

In 2017, the revised World Health Organization was published. Regarding myeloproliferative neoplasms, histological findings of bone marrow biopsy is becoming more important for diagnosis. This article highlights particularly the morphology of megakaryocytes and evaluation of myelofibrosis for pathological diagnosis, and immunohistochemistry which can detect somatic mutation.

Sphingosine-1-phosphate receptor 1 as a prognostic biomarker and therapeutic target for patients with primary testicular diffuse large B-cell lymphoma.

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.

WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome.

Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.