Ocular cicatricial pemphigoid following Dipeptidyl Peptidase-4 inhibitor use: A case report.

Purpose: To report a rare Ocular Cicatricial Pemphigoid (OCP) case in a patient taking a Dipeptidyl Peptidase-4 Inhibitor (DPP-4 inhibitor), a medication used for the management of type 2 diabetes, for at least six years. Observations: A 64-year-old male presented with refractory bilateral conjunctival inflammation and ocular discharge that had persisted for two months, despite multiple prior therapies for presumed bacterial conjunctivitis. Upon initial examination, clinical findings strongly suggested OCP, and he had elevated levels of anti-BP180 antibodies. Despite receiving systemic treatments such as steroid pulse therapy and therapeutic plasma exchange after discontinuing DPP-4 inhibitors, his condition progressively worsened, with manifestations such as forniceal shortening in his left eye. Consequently, the patient required keratoepithelioplasty, amniotic membrane transplantation in his left eye, and bilateral eyelid entropion surgery. His condition initially worsened for a time after discontinuing the DPP-4 inhibitor, but it gradually improved over time, and ocular surface surgical intervention was not required in the right eye. Conclusions and Importance: The findings in this study demonstrate that severe refractory OCP may occur while taking the DPP-4 inhibitor, thus indicating that a detailed interview regarding medications is essential for patients with ocular pemphigoid, especially those with type 2 diabetes.

Orbito-cranial schwannoma-a multicentre experience.

OBJECTIVES: To describe the features, management approaches, and outcomes of orbito-cranial schwannomas. METHODS: Retrospective review of ten patients with orbito-cranial schwannomas managed in six orbital services over 22 years. Data collected included demographics, presenting features, neuroimaging characteristics, histology, management approach, complications, and outcomes. RESULTS: Mean age of the patients was 41.4 ± 19.9 years, and 6 (60%) were females. The majority presented with proptosis (90%), limited extraocular motility (80%), eyelid swelling (60%), and optic neuropathy (60%). Most lesions (80%) involved the entire anterior-posterior span of the orbit, with both intra- and extraconal involvement. All tumours involved the orbital apex, the superior orbital fissure, and extended at least to the cavernous sinus. Surgical resection was performed for all. Seven (70%) of the tumours were completely or subtotally resected combining an intracapsular approach by an orbital-neurosurgical collaboration, with no recurrence on postoperative follow-up (6-186 months). Three underwent tumour debulking. Of these, two remained stable on follow-up (6-34 months) and one showed progression of the residual tumour over 9 years (cellular schwannoma on histology) necessitating stereotactic radiotherapy (SRT) for local control. Adjuncts to the orbito-cranial resection included perioperative frozen section (n = 5), endoscopic transorbital approach (n = 2), and image-guided navigation (n = 1). Post-surgical adjuvant SRT was used in three subjects. CONCLUSIONS: These results highlight the possibility of successful surgical control in complex orbito-cranial schwannomas. A combined neurosurgical/orbital approach with consideration of an intracapsular resection is recommended. Recurrence may not occur with subtotal excision and observation may be reasonable. Adjunctive SRT for progression or residual tumour can be considered.

Watchful waiting is an acceptable treatment option for asymptomatic primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: A retrospective study.

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common subtype of indolent ocular adnexal lymphomas. Although radiotherapy (RT) is the standard of care for localized POAML, it can occasionally lead to permanent side effects. Other treatment strategies, such as rituximab (R) monotherapy and immunochemotherapy, have been used for POAML treatment, but their long-term benefits and relative merits remain unclear. While watchful waiting (WW) is a potential option for some indolent lymphomas, the benefits of WW for POAML patients are also unclear. METHODS: We here retrospectively analyzed 75 patients who were diagnosed with POAML between 2008 and 2019 in the institutions of the Kyoto Clinical Hematology Study Group. RESULTS: Commonly involved sites were conjunctiva (42.7%), orbit (36.0%), and lacrimal gland (12.0%), and most patients (92.0%) presented with Ann Arbor stage IE disease. The treatment strategy was selected at the physicians' discretion. More patients without subjective symptoms by tumor mass were subjected to WW (29 patients), while more patients with tumor-derived subjective symptoms were treated by tumor-directed therapy (24 received focal RT, and 19 received R monotherapy). Complete response rates were 79.2% and 42.1% in the RT and R groups, respectively. At 60 months of follow-up, the estimated proportions of POAML patients not requiring new treatment were 69.4%, 85.2%, and 53.8% in the WW, RT, and R groups, respectively. There were no significant differences in the time to start a new treatment between WW and RT groups (median: both not reached [NR], p = 0.187) and between WW and R groups (median: NR vs. 69.0 months, p = 0.554). No specific predictive factor for the future need of treatment was identified in the WW group. CONCLUSION: Our results demonstrate WW may be an acceptable treatment option for POAML, especially for asymptomatic patients.

Adipose tissue:Critical contributor to the development of prostate cancer.

The prostate is surrounded by periprostatic adipose tissue. Although adipose tissue was thought to play limited physiological roles, it has recently been recognized as an active endocrine organ, secreting growth factors and adipokines. Epidemiologically, obesity is associated with prostate cancer progression. A major mechanism to explain the link between obesity and cancer includes the insulin and insulin-like growth factor (IGF)-1 axis, sex steroids, and adipokines. When prostate cancer cells invade periprostatic adipose tissue, adipose tissue contributes to create the tumor microenvironment, mainly via adipokine secretion. Furthermore, direct crosstalk between adipocytes and cancer cells can exist. We showed that fatty acid-binding protein 4 (FABP4) released from adipocytes was taken up into prostate cancer cells and may act as a carrier of an energy source for the invasion. Bone is an adipocyte-rich organ and is the common metastatic site of prostate cancer. In the microenvironment of bone metastases, tumor cells, osteoblasts, osteoclasts, adipocytes, and other stromal cells are interacting with one another and organizing a complex system. Thus, growing evidence implicates adipose tissue as a critical contributor to the development of prostate cancer. A deeper understanding of the mechanisms leads to more effective therapeutic strategies for prostate cancer. J. Med. Invest. 65:9-17, February, 2018.

A case of atypical type A thymoma with vascular invasion and lung metastasis.

We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.

Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma.

Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs.

A case of polypoid endometriosis with malignant transformation.

Polypoid endometriosis is a benign, rare variant of endometriosis which forms multiple polypoid nodules in the female pelvis mimicking malignant tumors; however, it may rarely cause malignant transformation. We report magnetic resonance imaging findings of a case of polypoid endometriosis with malignant transformation. Multiple high-signal intensity polypoid nodules in the cul-de-sac surrounded by low-signal intensity rim-like fibrous adhesion protruding to the posterior wall of the uterine body were demonstrated on T2-weighted images. The polypoid nodules showed weak contrast enhancement compared with that of uterine myometrium on post-contrast T1-weighted images, and slight high signal intensity on diffusion-weighted images with relatively high mean apparent diffusion coefficient. Reported cases of polypoid endometriosis showed intense contrast enhancement similar to that of uterine myometrium, and weak contrast enhancement similar to that of endometrial carcinoma may be suggestive for malignant transformation of polypoid endometriosis.

A pedunculated submucosal lesion in the stomach with inverted downgrowth.

A 70-year-old man with a gastric lesion was referred to our hospital because of an unusual pedunculated lesion in the gastric body. Endoscopic ultrasound showed scattered cystic lesions within a heterogeneous area confined to the submucosal layer. Endoscopic mucosal resection was performed to obtain a precise diagnosis, as well as for removal. The lesion was histopathologically diagnosed as a heterotopic submucosal gland. We herein describe this rare type of gastric polyp and provide a literature review.

Development of a support skill scale in insulin therapy: a nationwide study in Japan.

The aim of this cross-sectional, nationwide study in Japan was to develop a support skill scale for insulin therapy (IT-SSS) and to evaluate its validity and reliability. The sample consisted of 1604 nurses at 123 hospitals throughout the country. The factor validity, known-group validity, convergent validity, discriminant validity and internal consistency of IT-SSS were assessed. IT-SSS consisted of 26 minimum and 25 standard support skills. They included 4 subscales for minimum skills: management strategy for hypoglycemia, education about insulin injection technique, individual assessment and support about insulin rejection, and collaboration with medical professionals and patient/family. Three subscales for standard skills: apprehensions concerning the will and emotion of the patient, management for blood glucose control, and coordination in insulin management. Cronbach's alpha coefficient was between 0.75 and 0.90, suggesting strong internal consistency. Multitrait analysis showed that convergent validity was complete, and discriminant validity was found to be almost complete in both minimum and standard skill scales (scaling success rates of 97.6% and 98.7% across all subgroups, respectively). Known group analysis clearly showed that specialist nurses have significantly higher skills than general nurses. These findings indicate that IT-SSS has a reasonable factor validity, convergent validity, discriminant validity, known group validity, and internal consistency.

Pituitary adenomas that show a faint GH-immunoreactivity but lack fibrous body: Pit-1 adenoma with endocrinologically low activity.

Growth hormone (GH)-producing pituitary adenomas have been classified into densely and sparsely granulated adenomas. The latter are chromophobic with weak GH-positivity and characteristically possess fibrous body (FB), aggregation of cytokeratin filaments. We report eight cases of unusual chromophobic adenomas. GH-immunoreactivity was detected in most adenoma cells in five cases and scattered in three cases. However, it appeared much weaker than that seen in ordinary GH-producing adenomas because of spotty immunoreactivity. Although intracytoplasmic organelles were well-developed, secretory granules were small and sparse. FB was not identified in any cases. Thyroid-stimulating hormone was positive in four cases. Pit-1 protein was positive in all eight cases. A weak labeling with GH probe was detected in two of two cases examined by in situ hybridization. Acromegalic features were evident in four cases, while mild or absent in four cases. GH levels were below 5 microg/l in four cases and 5-10 microg/l in the remaining cases. Macroadenomas and invasive adenomas were seen in seven and six cases, respectively.Pituitary adenomas that show a faint GH-immunoreactivity but lack FB do not fit the established classification. These adenomas may be a distinct pituitary adenoma type of Pit-1 lineage with endocrinologically low activity.

Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.