Pancreatic Metastases from Renal Cell Carcinoma Showing Atypical Imaging Findings.

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.

Phenotypic and molecular characterization of novel pulmonary adenocarcinoma cell lines established from a dog.

Canine pulmonary adenocarcinoma (PAC) resembles human lung tumors in never-smokers, but it is rarer than human pulmonary adenocarcinoma. Therefore, research on canine PAC is challenging. In the present study, we successfully established various novel canine PAC cell lines from a single lesion in a dog, including two parent cell lines and fourteen cloned cell lines, and characterized their cellular properties in vitro. Several of these cell lines showed epithelial-mesenchymal transition (EMT)-like and/or cancer stem cell (CSCs)-like phenotypes. We additionally assessed the sensitivity of the cells to vinorelbine in vitro. Three clonal lines, two of which showed EMT- and CSC-like phenotypes, were resistant to vinorelbine. Furthermore, we evaluated the expression and activation status of EGFR, HER2, and Ras signaling factors. The findings indicated that the cell lines we established preserved the expression and activation of these factors to varying extents. These novel canine PAC cell lines can be utilized in future research for understanding the pathogenesis and development of treatments for canine PAC.

The Usefulness and Reliability of Coagrasper for Artery Bleeding during Endoscopic Necrosectomy.

Although endoscopic necrosectomy (EN) is a less invasive therapy for walled-off necrosis (WON), arterial bleeding can occur during EN. A 60-year-old man with infected WON underwent the EN procedure. During EN, the artery in the WON cavity was injured. As the artery was directly visible, we grasped it using a Coagrasper and coagulated the bleeding point. However, the bleeding was aggravated after coagulation owing to an extension of the vessel damage. The entire vessel was grasped, and complete hemostasis was achieved. The Coagrasper is useful for managing arterial bleeding; however, it should be employed only on the basis of its characteristics and in suitable scenarios.

Comparison of 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma using endoscopic ultrasound fine-needle aspiration.

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.

A Case of Early-Stage Gallbladder Cancer, Positive for ALDH1A1, Which Arose from Adenomyomatosis of the Gallbladder.

Adenomyomatosis (ADM) of the gallbladder is a condition characterized by the proliferation of Rokitansky-Aschoff sinus (RAS), in which the epithelium of the gallbladder extends into the muscular layer, causing a thickening of the gallbladder wall. Although ADM is generally considered not to be a precancerous lesion of gallbladder cancer, there are some reports of cases of gallbladder cancer from ADM. Therefore, the relationship between ADM and gallbladder cancer remains controversial. We herein report a case of early-stage gallbladder cancer, BilIN3 (high grade), arising from ADM that was positive for ALDH1A1, an important marker of stem cells and cancer stem cells.

Histopathologic effect of in ovo exposure to methotrexate at early embryonic stage on optic tectum of Japanese quail (Coturnix japonica).

The optic tectum of Japanese quail embryos with in ovo exposure to methotrexate 100 ng/g egg on embryonic day 4 was examined from 3 to 24 hour after treatment. At 9 hour after methotrexate exposure, several apoptotic neuroepithelial cells appeared in the ventricular zone of the optic tectum; these increased in number and were diffusely distributed throughout all layers of the ventricular zone of the optic tectum at 12 hour. At 24 hour, neuroepithelial cells in the ventricular zone of the optic tectum were eliminated and showed sparse cell density. Throughout the experimental period, proliferation of neuroepithelial cells in the ventricular zone of the optic tectum of methotrexate-treated embryos was inhibited. These results suggest that neuroepithelial cells in the ventricular zone of the optic tectum in Japanese quail embryos can be affected by folic acid antimetabolites, methotrexate, at an early embryonic stage.

Evaluation of the Cell Block Method Using Overnight-Stored Bile for Malignant Biliary Stricture Diagnosis.

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

Effects of testosterone on rat placental development.

We investigated the morphological effects of testosterone on placental development in a rat model of polycystic ovarian syndrome (PCOS). Testosterone propionate (TP), which was subcutaneously administered to pregnant rats with 5 mg/animal from gestation day (GD) 14 to GD 18, induced a maternal weight reduction without mortality or clinical signs from GD 19 onwards. A decrease in fetal and placental weight, an increase in intrauterine growth retardation (IUGR) rates, and histological changes in the placenta were observed on GD 21 but not on GD15 or 17. Histopathologically, on GD 21, the trophoblast septa thickened, and the maternal sinusoids were narrowed in the labyrinth zone, resulting in a small placenta. Additionally, the placental weight, thickness, and histological morphology in the labyrinth zone on GD 21 in the TP-treated group were nearly identical to those on GD 17 in the control and TP-treated groups. Therefore, it was assumed that the testosterone-induced small placenta was induced in association with the developmental inhibition of the fetal part of the placentas from GD 17 onwards.

The Outcome and CT Findings of Low-Dose Intensity Modulated Radiation Therapy with SQAP in a Cat with Thymoma.

A 9-year-old male intact domestic cat weighing 4.6 kg was referred for tachypnea. A large mass was visible in computed tomography (CT) scans of the thoracic cavity. A histopathological evaluation of the mass was consistent with thymoma. The cat was treated with 2 × 8 Gy intensity modulated radiation therapy and sulfoquinovosyl acyl propanediol (SQAP). Post radiation therapy (RT), the tumor structure appeared cystic in the CT, and the tumor volume decreased by approximately 80% after aspiration than that before aspiration. The tumor was removed surgically. RT treatment with SQAP made it possible to treat the thymoma with a low total radiation dose.

Sequential histological changes in the liver of medaka exposed to methylazoxymethaol acetate.

We performed a medaka bioassay for the carcinogenicity of methylazoxymethaol acetate (MAM-Ac) to examine the sequential histological changes in the liver from 3 days after exposure until tumor development. The medaka were exposed to MAM-Ac at a concentration of 2 ppm for 24 hours, and were necropsied at 3, 7, 10, 14, 21, 28, 35, 42, 49, 60, and 91 days after exposure. MAM-Ac induced four cases of hepatocellular adenoma and one case of hepatocellular carcinoma in 8 fish after 60 or 91 days of exposure. Histological changes in the liver until tumor development were divided into three phases. In the cytotoxic phase (1-10 days), MAM-Ac-exposed hepatocytes showed vacuolar degeneration and underwent necrosis and apoptosis, resulting in multiple foci of hepatocyte loss. In the repopulation phase (14-35 days), the areas of hepatocyte loss were filled with hepatic cysts and the remaining hepatocytes were surrounded by hepatic stellate-like cells (or spindle cells) and gradually disappeared. In the proliferation phase (42-91 days), the original hepatic parenchyma was regenerated and progressively replaced by regenerative hyperplastic nodules and/or liver neoplasms. The medaka retained a strong hepatocyte regenerative ability in response to liver injury. It is considered that this ability promotes the proliferation of initiated hepatocytes in multistep carcinogenesis and influences the development of liver tumor over a short period in medaka.

Hemostatic radiotherapy for inoperable gastric cancer: a pilot study.

OBJECTIVE: Standard treatment for progressive gastric cancer with bleeding includes hemostatic radiotherapy (RT); however, the only prospective study using a fixed dose with fractions during hemostatic RT did not introduce re-irradiation. Therefore, we determined the utility of RT including re-irradiation for gastric cancer. METHODS: In this study, 31 patients with gastric cancer and bleeding were treated with an initial dose of 20 Gy/5 fractions for the whole stomach and a salvage dose of 15 Gy/5 fractions for the partial stomach. Patients achieving hemostasis, defined as a stable hemoglobin level within 30 days following irradiation, were considered responders, whereas those with no cessation of bleeding and those with re-bleeding within 30 days of irradiation were considered non-responders. We evaluated response rate, disease-free survival, overall survival (OS), re-irradiation, and adverse events (AEs). RESULTS: The response rate of initial RT was 80% (25/31). 6 of the 25 patients underwent re-irradiation, and all 6 were responders (100%). The median OS was significantly different among the entire cohort and one-time irradiation and re-irradiation groups (91, 76, and 112 days, respectively). No AEs of grade ≥3 were observed. Initial low-dose RT followed by reirradiation was effective in reducing AEs and did not cause any further AEs. CONCLUSION: Hemostatic RT was an effective approach with low toxicity, and re-irradiation was effective and tolerable, with no patients developing severe AEs. Further, randomized controlled studies are warranted to determine the ideal dose and number of fractions for initial RT in patients with gastric cancer and bleeding. ADVANCES IN KNOWLEDGE: In this prospective study on hemostatic radiotherapy for gastric cancer, the response rate was 80% using a fixed dose of 20 Gy/5 fractions and the salvage dose of 15 Gy for re-bleeding was effective. Future comparative studies should include other doses with 20 Gy as a control.

The effects of ß-naphthoflavone on rat placental development.

The morphological effects of ß-naphthoflavone (ß-NF) on placental development in pregnant rats were examined. ß-NF, administered to pregnant rats intraperitoneally at 15 mg/kg bw from gestation day (GD) 9 to GD 14, had no effect on maternal body weight gain, mortality, or clinical sign. In the ß-NF-exposed rats, intrauterine growth retardation (IUGR) rates increased on GDs 17 and 21, although there was no effect on fetal mortality rate, fetal or placental weight, or external fetal abnormality. Histopathologically, ß-NF induced apoptosis and inhibition of cell proliferation of the trophoblastic septa in the labyrinth zone, resulting in its poor development. In the basal zone, ß-NF induced spongiotrophoblast apoptosis and delayed glycogen islet regression, resulting in their cystic degeneration. ß-NF-induced CYP1A1 expression was detected in the endothelial cells of the fetal capillaries in the labyrinth zone and in the endothelial cells of the spiral arteries in the metrial gland, but not in any trophoblasts. This indicates that CYP1A1 is inducible in the endothelial cells of the fetal capillaries in the labyrinth zone, and that these cells have an important role in metabolizing CYP1A1 inducers crossing the placental barrier.

Renal lesions in leptin receptor-deficient medaka (Oryzias latipes).

The aim of this study was to elucidate the renal lesions of leptin receptor-deficient medaka showing hyperglycemia and hypoinsulinemia and to evaluate the usefulness of the medaka as a model of diabetic nephropathy. Leptin receptor-deficient medaka at 20 and 30 weeks of age showed hyperglycemia and hypoinsulinemia; they also showed a higher level of plasma creatinine than the control medaka. Histopathologically, dilation of glomerular capillary lumina and of afferent/efferent arterioles was observed in leptin receptor-deficient medaka at 20 weeks of age, and then glomerular enlargement with cell proliferation and matrix expansion, formation of fibrin cap-like lesions, glomerular atrophy with Bowman's capsule dilation, and renal tubule dilation were observed at 30 weeks of age. These histopathological characteristics of leptin receptor-deficient medaka were similar to the characteristics of kidney lesions of human and rodent models of type II diabetes mellitus, making leptin receptor-deficient medaka a useful model of diabetic nephropathy.

Histopathologic features of melanocytic tumors in Xiphophorus melanoma receptor kinase (xmrk)-transgenic medaka (Oryzias latipes).

Melanocytic tumors in Xiphophorus melanoma receptor kinase (xmrk)-transgenic Carbio and HB11A strains of medaka were examined histopathologically at 7 months post-hatching. Medaka of both strains developed melanocytic tumors with a penetrance of 100%. In both strains, neoplastic cells containing intracytoplasmic melanin pigment granules showed significant invasive growth patterns. In addition, epithelioid neoplastic cells were arranged in solid nests, and spindle neoplastic cells were arranged in interlacing streams and bundles. Nuclear atypia, anisokaryosis, cellular pleomorphism, and the appearance of anaplastic giant cells containing multiple nuclei or a single nucleus were observed in neoplastic lesions in both medaka strains. However, neither strain exhibited mitotic figures or invasion of blood vessels by neoplastic cells. Based on these histopathologic findings, the tumors were diagnosed as malignant melanoma. This is the first report of detailed histomorphologic characteristics of malignant melanoma in xmrk-transgenic medaka.

Morphology and physiology of rat placenta for toxicological evaluation.

The placenta plays a pivotal role in fetal growth, and placental dysfunction and injury are associated with embryo/fetal toxicity. Histological examination of the rat placenta for safety evaluation provides valuable clues to the mechanisms of this toxicity. However, the placenta has specific and complex biological features unlike those of other organs, and placental structure dramatically changes depending on the time during the gestation period. Thus, time-dependent histopathological examination of the rat placenta should be performed based on the understanding of normal developmental changes in morphology and function. The placentas of rats and humans are both anatomically classified as discoid and hemochorial types. However, there are differences between rats and humans in terms of placental histological structure, the fetal-maternal interface, and the function of the yolk sac. Therefore, extrapolation of placental toxicity from rats to humans should be done cautiously in the evaluation of risk factors. This review describes the development, morphology, physiology, and toxicological features of the rat placenta and the differences between the rat and human placenta to enable accurate evaluation of reproductive and developmental toxicity in studies.

Ocular lesions in leptin receptor-deficient medaka (Oryzias latipes).

Ocular lesions in leptin receptor-deficient medaka were examined histopathologically at 10, 28, and 37 weeks post hatching. Leptin receptor-deficient medaka at 28 and 37 weeks old showed hyperglycemia and hypoinsulinemia. Histopathologically, vacuolation, swelling, fragmentation, and liquefaction of the lens fibers and dilatation of the retinal central veins, retinal capillaries, iridal veins and capillaries, and choroidal veins were observed in leptin receptor-deficient medaka at 28 and 37 weeks old. Thinning of the total retina, pigment epithelial layer, layer of rods and cones, outer granular layer, outer plexiform layer, inner granular layer, and inner plexiform layer was observed in leptin receptor-deficient medaka at 28 and 37 weeks compared with in control medaka. These histopathological characteristics in leptin receptor-deficient medaka are similar to characteristics in ocular lesions of rodent models for type II diabetes mellitus, making leptin receptor-deficient medaka a useful model of diabetic cataract and retinopathy.

Effects of methotrexate exposure on medaka (Oryzias latipes) testes.

For the purpose of clarifying the histopathological effects of methotrexate (MTX) on medaka testes, wild-type and homogenic p53-deficient male medaka at 4 to 6 months post-hatching were exposed to 0.25 mg/ml of MTX for 96 h with histopathological examination of testes at 24, 48, 72 and 96 h. At 72 and 96 h after the start of MTX exposure, numerous apoptotic cells were observed in the spermatogonia and spermatocytes, and the pyknotic cell rate and the TUNEL-positive and cleaved caspase-3-positive rates in the spermatogonia and spermatocytes of MTX-treated wild type medaka were higher compared with those in the control wild-type medaka. Starting at 48 h, the phospho-histone H3-positive rate in the spermatogonia and spermatocytes of was significantly lower in MTX-treated wild-type medaka than in control wild-type medaka. In homogenic p53-deficient medaka, apoptosis was not induced in the spermatogonia and spermatocytes by exposure to MTX. Starting at 48 h, the phospho-histone H3-positive rate in spermatogonia and spermatocytes of MTX-treated homogenic p53-deficient medaka was lower than in control homogenic p53-deficient medaka. Throughout the entire experimental period, there were no significant differences in phospho-histone H3-positive rates in the spermatogonia and spermatocytes between the MTX-treated homogenic p53-deficient medaka group and the MTX-treated wild-type medaka group. In the present study, spermatogonia and spermatocytes of medaka testes were sensitive to MTX at 0.25 mg/ml in the culture water, and MTX-induced apoptosis in the testes was dependent on p53 expression; however, inhibition of MTX-induced cell proliferation was independent of p53 expression.

Effects of cadmium exposure on Iberian ribbed newt (Pleurodeles waltl) testes.

To characterize the histomorphologic effects of cadmium on adult newt testes, male Iberian ribbed newts (6 months post-hatching) were intraperitoneally exposed to a single dose of 50 mg/kg of cadmium, with histologic analysis of the testes at 24, 48, 72, and 96 h. Beginning 24 h after cadmium exposure, apoptosis of spermatogonia and spermatocytes was observed, and congestion was observed in the interstitial vessels of the testes. Throughout the experimental period, the rates of pyknotic cells and TUNEL and cleaved caspase-3 positivity were significantly higher in the spermatogonia and spermatocytes of cadmium-treated newts compared with control newts. There were no significant differences between cadmium-treated and control newts in phospho-histone H3 positivity in the spermatogonia and spermatocytes. These results suggest that spermatogonia and spermatocytes in adult Iberian ribbed newts are highly sensitive to cadmium. This is the first report of the histomorphologic characteristics of cadmium-induced testicular dysfunction in newts.

Effect of dibutyltin on placental and fetal toxicity in rat.

In order to elucidate the effect of chorioallantoic and yolk sac placenta on the embryonic/fetal toxicity in dibutyltin dichloride (DBTCl)-exposed rats, we examined the histopathological changes and the tissue distribution of dibutyltin in the placentas and embryos. DBTCl was orally administered to the groups at doses of 0 mg/kg during gestation days (GD)s 7-9 (control group) and 20 mg/kg during GDs 7-9 (GD7-9 treated group), and GDs 10-12 (GD10-12 treated group). The total fetal mortality was increased, and malformations characterized by craniofacial dysmorphism were detected in the GD7-9 treated group. The embryonic/fetal weight and placental weight showed a decrease in both DBTCl-treated groups. Histologically, some embryos on GD 9.5 in the GD7-9 treated group underwent apoptosis without any changes of yolk sac. In the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS), tin was detected in the embryo, allantois, yolk sac, ectoplacental cone and decidual mass surrounding the conceptus on GD 9.5 in the GD7-9 treated group. Thus, it is considered that the embryo in this period is specifically sensitive to DBTCl-induced apoptosis, compared with other parts. The chorioallantoic placentas in both DBTCl-treated groups showed the developmental delay and hypoplasia in the fetal parts of placenta, resulting from apoptosis and mitotic inhibition. Thus, it was speculated that the DBTCl-induced malformations and fetal resorption resulted from the apoptosis in the embryo caused by the direct effect of DBTCl. The DBTCl-induced lesions in the chorioallantoic placenta were a non-specific transient developmental retardation in the fetal parts of placenta, leading to intrauterine growth retardation.