Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study.

BACKGROUND: Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus. METHODS: Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. RESULTS: CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20-/-) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks. CONCLUSIONS: This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20-/- mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

An invaginated pancreaticogastrostomy following subtotal stomach-preserving pancreaticoduodenectomy: A prospective observational study.

BACKGROUND/OBJECTIVE: Postoperative pancreatic fistula (POPF) leads to life-threatening complications after pancreaticoduodenectomy (PD). Pancreaticogastrostomy (PG) often adopted as a reconstruction technique after PD to prevent POPF. Delayed gastric emptying (DGE) following PD is the most common complication that compromises the quality of life. Subtotal stomach-preserving PD (SSPPD) preserves the pooling ability of the stomach and minimize the occurrence of DGE. This study aimed to describe our PG technique following SSPPD and evaluate the perioperative outcomes. METHODS: The study included patients who underwent PG following SSPPD from August 2013 to July 2020 at our institution. An invaginated PG was performed by one-layer eight interrupted sutures with a lost stent. Patients' demographics and perioperative outcomes were documented. RESULTS: This technique was applied in 72 patients with a median age of 75 years. The median operative time was 342 min. The clinically relevant POPF, DGE and post-pancreatectomy hemorrhage was 4 (5.6%), 5 (6.9%), and 10 (13.9%), respectively. Although the drain fluid amylase concentration on postoperative day 3 was significantly higher in clinically relevant POPF (CR-POPF) positive group (median, 2006 U/L vs. 74 U/L in CR-POPF negative group, p = 0.002), none of the risk factors including disease pathology, pancreatic duct diameter, texture of pancreas and excessive blood loss were significantly associated with CR-POPF. Other morbidity ≥ Clavien-Dindo classification II occurred in 29 patients (40.3%). The 90-days operative mortality was two (2.8%). CONCLUSIONS: This novel method of one-layer invaginated PG following SSPPD is safe and dependable procedure with acceptable morbidity and mortality.

Pancreaticoduodenectomy after transcatheter aortic valve implantation in an elderly patient with severe aortic stenosis and pancreas cancer: A case report.

INTRODUCTION AND IMPORTANCE: Not only pancreatic cancer but also aortic stenosis (AS) is increasing with the aging population. There is no optimal strategy for elderly patients with both pancreatic cancer and AS. We report a case of pancreatic head cancer with severe AS undergoing pancreaticoduodenectomy (PD) after transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: An 88-year-old woman was referred to our hospital because of severe AS with symptoms of heart failure. Preoperative examination revealed resectable pancreatic head cancer, so TAVI was performed before PD to reduce the perioperative risk. The patient underwent PD 34 days after TAVI, with no significant postoperative complications, and was transferred to the other hospital for rehabilitation on postoperative day 45. No recurrence was observed at more than 7 months without adjuvant therapy. CLINICAL DISCUSSION: Aortic valve replacement (AVR) is recommended before non-cardiac surgery in patients with symptomatic severe AS. Surgical aortic valve replacement (SAVR) is the standard treatment. However, owing to the highly invasive procedure and increased perioperative risk, SAVR is usually avoided in elderly patients with malignancy and severe AS. We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with both severe AS and pancreatic head cancer. To our knowledge, this is the first case report of PD after TAVI in a patient with severe AS. CONCLUSION: We demonstrated that TAVI followed by PD could be safely performed in high-risk elderly patients presenting with severe AS and co-existing malignancy.

Impact of antithrombotic therapy on the outcomes with focus on bleeding and thromboembolic events in patients undergoing pancreticoduodenectomy.

BACKGROUND: We investigated perioperative outcomes of pancreaticoduodenectomy (PD) in patients receiving antithrombotic therapy (ATT) with a focus on the incidence of perioperative bleeding and thromboembolic complications. METHODS: A total of 77 patients who underwent PD at our institution between 2013 and 2019 were retrospectively reviewed. Clinical findings and surgical outcomes including bleeding and thromboembolic complications were compared in patients with or without ATT. Interruption of ATT and perioperative heparin bridging were based on our hospital protocol. RESULTS: Among ATT (30) and non-ATT (47) groups, ATT group had a significantly higher age and history of cardiocerebrovascular diseases. No significant difference was observed in intraoperative and post-pancreatectomy haemorrhage (PPH) between the groups. ATT group was associated with a significantly higher rate of post-operative complications, Clavien-Dindo classification ≥II and thromboembolic events. Operative mortality in ATT and non-ATT groups was 2 (6.7%) and 1 (2.1%), respectively. There was no significant association between ATT and excessive intraoperative blood loss (≥1000 mL), PPH (≥grade B) and thromboembolic complications (Clavien-Dindo classification ≥II). CONCLUSION: In patients with ATT, PD is a feasible procedure with no major impact on intraoperative bleeding or PPH.

Simultaneous Surgery for Inferior Vena Cava Leiomyosarcoma with Multiple Hepatic Metastases: A Justified Challenge.

BACKGROUND Leiomyosarcoma of inferior vena cava (IVC), a rarely encountered malignancy originating from the smooth muscle cells of media of the IVC, frequently metastasize to the liver. The suggested treatment of choice of IVC leiomyosarcoma is radical en-bloc excision aimed to obtain a negative resection margin. There are a few reported cases of surgical management in patients with liver metastasis from IVC leiomyosarcoma. CASE REPORT This report describes a simultaneous surgical approach for a case of IVC leiomyosarcoma with multiple liver metastases followed by chemotherapy. CONCLUSIONS Tumor volume reduction surgery of metastatic lesions combined with radical resection of the primary tumor may provide better survival benefit in patients with advanced IVC leiomyosarcoma.

Re-expression of Sall1 in podocytes protects against adriamycin-induced nephrosis.

The highly conserved spalt (sal) gene family members encode proteins characterized by multiple double zinc finger motifs of the C2H2 type. Humans and mice each have four known Sal-like genes (SALL1-4 in humans and Sall1-4 in mice). Sall1 is known to have a crucial role in kidney development. To explore the significance of Sall1 in differentiated podocytes, we investigated podocyte-specific Sall1-deficient mice (Sall1 KOp°d°/p°d°) using a podocin-Cre/loxP system and siRNA Sall1 knockdown (Sall1 KD) podocytes. Under physiological conditions, Sall1 KOp°d°/p°d° mice exhibited no proteinuria during their lifetime, but foot-process effacement was detected in some of the podocytes. To elucidate the role of Sall1 in injured podocytes, we used an adriamycin (ADR)-induced model of nephrosis and glomerulosclerosis. Surprisingly, the expression of Sall1 was elevated in control mice on day 14 after ADR injection. On day 28 after ADR injection, Sall1 KOp°d°/p°d° mice exhibited significantly higher levels of proteinuria and higher numbers of sclerotic glomeruli. Differentiated Sall1 KD podocytes showed a loss of synaptopodin, suppressed stress fiber formation, and, ultimately, impaired directed cell migration. In addition, the loss of Sall1 increased the number of apoptotic podocytes following ADR treatment. These results indicated that Sall1 has a protective role in podocytes; thus, we investigated the endoplasmic reticulum stress marker GRP78. GRP78 expression was higher in ADR-treated Sall1 KOp°d°/p°d° mice than in control mice. Sall1 appeared to influence the expression of GRP78 in injured podocytes. These results suggest that Sall1 is associated with actin reorganization, endoplasmic reticulum stress, and apoptosis in injured podocytes. These protective aspects of Sall1 re-expression in injured podocytes may have the potential to reduce apoptosis and possibly glomerulosclerosis.

Metastasis of colon cancer to the thyroid and cervical lymph nodes: a case report.

The incidence of thyroid metastasis among colorectal cancer patients is extremely rare. We report a case of colonic adenocarcinoma metastasis to the thyroid gland with treatment of lung and liver metastases, in a 61-year-old woman with a history of colon cancer. She showed a thyroid mass related to a 3-month history of hoarseness. Physical and imaging examinations disclosed a diffuse large thyroid mass with swollen cervical lymph nodes. Fine-needle aspiration cytology of the thyroid mass suggested malignancy. The patient underwent total thyroidectomy. Histopathological examination and immunohistochemical staining revealed adenocarcinoma, which was consistent with a diagnosis of metastases from primary colon cancer to the thyroid and cervical lymph nodes. At 2 years after thyroid surgery, the patient has been continuing outpatient chemotherapy for the lung and liver metastases. Thyroidectomy appeared to both relieve the patient and prevent local symptoms.

Gallbladder small cell carcinoma: a case report and literature review.

Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.

Deletion of the Fc receptors gamma chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet.

AIMS: To clarify the role of Fc receptors (FcR) for immunoglobulin in endothelial dysfunction induced by hypercholesterolaemia, we evaluated the effect of deletion of the FcR gamma chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR gamma(-/-) mice compared with that in wild-type mice. METHODS AND RESULTS: Plasma cholesterol levels of those on the high-fat diet were significantly increased compared with those on the normal chow diet in both groups of mice. Endothelium-dependent relaxation of the aortic ring with acetylcholine in wild-type mice was significantly reduced by the high-fat diet (ED(50): 0.22 vs. 0.43 nM, P < 0.002), whereas the relaxation in FcR gamma(-/-) mice was not inhibited (ED(50): 0.22 vs. 0.23 nM, NS). Furthermore, superoxide detection by dihydroethidium-derived fluorescence and immunohistochemical staining of p22phox expression were significantly increased in wild-type mice fed on the high-fat diet, while these oxidative stresses in FcR gamma(-/-) mice were not enhanced by the high-fat diet. Oil Red O-staining showed no significant lipid accumulation at the aortic sinus in both groups of mice. CONCLUSION: This study demonstrates that the deletion of the FcR gamma chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR gamma(-/-) mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolaemia.