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Among pancreatic cystic lesions, mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas are precursor lesions of pancreatic adenocarcinoma. IPMN is characterized by intraductal papillary proliferation of mucin-producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified as the main duct type (MD-IPMN), mixed type and the branch duct type (BD-IPMN) according to the location of involvement, and into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to the histomorphological and immunohistochemical characteristics. Most patients with MD-IPMN undergo tumor resection due to moderate to high risk of malignancy. Patients with BD-IPMN who do not undergo resection may develop malignant change, and concomitant separate pancreatic cancer occurs in 2-10% of patients with IPMN. Patients with BD-IPMN who do not undergo resection should do careful surveillance including endoscopic ultrasound sonography for the early detection of malignant change and separate pancreatic cancer.

The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks. Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain, and it expands the utility of drugs by bypassing the blood–brain barrier (BBB). In addition, uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes, pointing to a critical issue still to be overcome. Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications, it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures, which differ from two-dimensionally fabricated shank-type neural probes. Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality. We fabricated a microfluidic interconnection cable (µFIC) and integrated it with a flexible penetrating microelectrode array (FPMA) that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base. We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection. This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.

Most pancreatic carcinoma is ductal adenocarcinoma. Primary pancreatic clear cell carcinomas composed almost entirely of clear tumor cells are very rare. We present a case of a 72-year-old man with a pancreatic mass, which was detected on abdominal computed tomography (CT). He had no symptoms and no abnormal findings on physical examination; however, he had a history of hepatitis B, hepatitis C, and hepatocellular carcinoma. He had received anti-viral treatment and radiofrequency ablation twice until 2 years prior. One year prior, follow-up contrast-enhanced abdominal CT revealed a newly developed pancreatic mass. Laparoscopic radical antegrade modular pancreato-splenectomy was performed. An ill-defined white-to-tan firm solid mass was observed in the pancreas, approximately 4.3 cm in diameter. The tumor cells showed >95% clear cell features, with a large round to oval nuclei and abundant clear cytoplasms, and well-defined cell membranes. Immunohistochemical staining revealed that the tumor cells were positive for cytokeratin 7, cytokeratin 19, HNF-1β, MUC-1, and p53. We excluded the possibility of metastatic clear renal cell carcinoma, neuroendocrine carcinoma, perivascular epithelioid cell tumor, malignant melanoma, and sarcoma because of the negativity for vimentin, chromogranin, synaptophysin, and HMB45. Consequently, he was diagnosed as having primary clear cell carcinoma of the pancreas and was treated with postoperative radiotherapy. Two months later, abdominal CT was suspicious for local recurrence at the resection margin. Additional adjuvant FOLFIRINOX chemotherapy was carried out 12 times. The patient is still alive after his third radiofrequency ablation for the newly-developed hepatic mass. Immunohistochemical staining for MUC-1 and HNF-1β, as well as histologic feature is very helpful for the diagnosis of primary pancreatic clear cell carcinoma with imaging methods for metastasis exclusion.

The most common malignant tumor of the pancreas is ductal adenocarcinoma. Focal clear cell changes in the ductal component of pancreatic ductal adenocarcinoma are rarely observed. Clear cell carcinomas composed almost entirely of clear tumor cells are very rare. We present a case of a 72-year-old man with a pancreatic mass, which was detected on abdominal computed tomography (CT), and a history of hepatitis B, hepatitis C, and hepatocellular carcinoma. He had received treatment with Zeffix, peginterferon, ribavirin, and radiofrequency ablation twice until 2 years prior. One year prior, follow-up contrast-enhanced abdominal CT revealed a newly developed pancreatic mass. Laparoscopic radical antegrade modular pancreato-splenectomy was performed under the clinical diagnosis of pancreatic ductal adenocarcinoma. An ill-defined white-to-tan firm solid mass was observed in the pancreas, approximately 2.0 cm in diameter. The tumor cells showed > 90 % clear cell features, with large round to oval nuclei and abundant clear cytoplasms, and well-defined cell membranes. Immunohistochemical staining revealed that the tumor cells were positive for pan-cytokeratin, cytokeratin 7, cytokeratin 19, HNF-1β, MUC-1, and p53. We excluded the possibility of metastatic clear renal cell carcinoma, neuroendocrine carcinoma, perivascular epithelioid cell tumor, malignant melanoma, and sarcoma because immunohistochemical staining of the tumor cells did not reveal the presence of vimentin, chromogranin, synaptophysin, and HMB45. Consequently, his condition was diagnosed as primary clear cell carcinoma of the pancreas, and he received postoperative radiotherapy and folfirinox chemotherapy after surgery. However, 11 months after surgery, a newly developed hepatic metastatic lesion was detected.

In patients with thyroid nodules, if the cervical lymph nodes gradually enlarge, a histological confirmation is required to rule out malignancy. Here is a case of benign intranodal thyroid tissue with cystic changes resembling lymph node metastasis of a papillary thyroid carcinoma. A 47-year-old man received ethanol sclerotherapy because of repeated enlargement of the thyroid gland 2 years prior to presentation. Subsequently, the patient underwent abscess removal from the deep neck and partial lobectomy of the attached left thyroid gland. Two months before the visit, extensive cervical lymphadenopathy was detected on ultrasonography (US) and computed tomography (CT). Total thyroidectomy and cervical lymph node dissection were performed to differentiate between metastatic papillary carcinoma of the thyroid gland and benign thyroid inclusions. Microscopic examination revealed multiple variable-sized nodules of benign thyroid follicles with cystic changes in both thyroid glands and bilateral cervical lymph nodes. An occult papillary microcarcinoma strongly positive for HBME-1 was also observed in the left thyroid lobe. However, the benign intranodal thyroid tissue was negative in both the real-time PCR-based BRAF V600E mutation test and HBME-1 immunohistochemical stain. Similarly, benign intranodal thyroid tissue can be enlarged by multiple cystic changes in a large number of lymph nodes along the neck node chain. For the differentiation of metastatic thyroid papillary carcinoma, real-time PCR-based BRAF V600E mutation test and HBME-1 immunohistochemical staining in addition to histological examination are helpful.

Adrenal mixed corticomedullary tumors (MCMTs) are single tumor masses composed of an intimately admixed population of both adrenal cortical cells and medullary components. Most medullary tumor components are pheochromocytomas; however, MCMTs composed of ganglioneuroma and adrenal cortical adenoma are extremely rare. The current case is a rare case of adrenal MCMT composed of ganglioneuroma and adrenal cortical adenoma with primary aldosteronism.A 49-year-old male was admitted because of hypokalemia and an adrenal mass. He was diagnosed with hypertension in his 20s and was taking blood pressure medications.Plasma aldosterone concentration 376.5 pg/dL (normal 37.8~233.0 pg/mL) and potassium 2.8 mmol/L (normal 3.4~4.9 mmol/L) were detected. The aldosterone-to-renin ratio [the ratio of plasma aldosterone concentration (ng/dL) to PRA (ng/mL/hour)] was 38. The saline loading test showed that serum aldosterone (49.4 ng/dL) was not suppressed, compared with the basal level (28.4 ng/dL). The adrenal venous sampling test showed that the aldosterone level markedly increased to 1521.2 pg/mL. Abdominal computed tomography revealed an enlarged relatively well-circumscribed multinodular mass (35 × 13 × 30 mm) in the right adrenal gland.Laparoscopic right adrenalectomy was performed under the clinical diagnosis of a functioning adrenal cortical adenoma.After laparoscopic right adrenalectomy, the serum aldosterone and renin levels returned to normal. The patient maintained a normal aldosterone level without recurrence for 16 months.Adrenal MCMTs of the ganglioneuroma and cortical adenomas in the ipsilateral adrenal gland are extremely rare. Adrenal MCMTs exhibit benign clinical behavior, with no metastasis or death due to the tumor. With the development of diagnostic imaging technology, it is possible to identify mixed tumors. However, surgical resection of adrenal gland is a common treatment and a final diagnosis should be made based on the pathological results after surgery. Because this is to rule out the occurrence of rare malignant tumors and confirm the pattern of mixed tumors.

Objective. Neural interfaces are an essential tool to enable the human body to directly communicate with machines such as computers or prosthetic robotic arms. Since invasive electrodes can be located closer to target neurons, they have advantages such as precision in stimulation and high signal-to-noise ratio (SNR) in recording, while they often exhibit unstable performance in long-term in-vivo implantation because of the tissue damage caused by the electrodes insertion. In the present study, we investigated the electrical functionality of flexible penetrating microelectrode arrays (FPMAs) up to 3 months in in-vivo conditions. Approach. The in-vivo experiment was performed by implanting FPMAs in five rats. The in-vivo impedance as well as the action potential (AP) amplitude and SNR were analyzed over weeks. Additionally, APs were tracked over time to investigate the possibility of single neuron recording. Main results. It was observed that the FPMAs exhibited dramatic increases in impedance for the first 4 weeks after implantation, accompanied by decreases in AP amplitude. However, the increase/decrease in AP amplitude was always accompanied by the increase/decrease in background noise, resulting in quite consistently maintained SNRs. After 4 weeks of implantation, we observed two distinctive issues regarding long-term implantation, each caused by chronic tissue responses or by the delamination of insulation layer. The results demonstrate that the FPMAs successfully recorded neuronal signals up to 12 weeks, with very stably maintained SNRs, reduced by only 16.1% on average compared to the first recordings, although biological tissue reactions or physical degradation of the FPMA were present. Significance. The fabricated FPMAs successfully recorded intracortical signals for 3 months. The SNR was maintained up to 3 months and the chronic function of FPMA was comparable with other silicon based implantable electrodes.

For implantable devices, Parylene C (hereafter referred to as Parylene) has shown promising properties such as flexibility, biocompatibility, biostability, and good barrier properties. Parylene-based flexible interconnection cable (FIC) was previously developed to connect a flexible penetrating microelectrode array (FPMA) with a recording system. However, Parylene-based FIC was difficult to handle and prone to damage during the implantation surgery because of its low mechanical strength. To improve the mechanical properties of the FIC, we suggest a mechanically enhanced flexible interconnection cable (enhanced FIC) obtained using a combination of Parylene and polyimide. To investigate the long-term stability of the enhanced FIC, Parylene-only FIC, and enhanced FIC were tested and their mechanical properties were compared under an accelerated aging condition. During the course of six months of soaking, the maximum strength of the enhanced FIC remained twice as high as that of the Parylene-only FIC throughout the experiment, although the mechanical strength of both FICs decreased over time. To show the capability of the enhanced FIC in the context of nerve signal recording as a part of a neural interfacing device, it was assembled together with the FPMA and custom-made wireless recording electronics. We demonstrated the feasibility of the enhanced FIC in an in vivo application by recording acute nerve signals from canine sciatic nerves.