De Novo Glycan Display on Cell Surfaces Using HaloTag: Visualizing the Effect of the Galectin Lattice on the Lateral Diffusion and Extracellular Vesicle Loading of Glycosylated Membrane Proteins.

Glycans cover the cell surface to form the glycocalyx, which governs a myriad of biological phenomena. However, understanding and regulating glycan functions is extremely challenging due to the large number of heterogeneous glycans that engage in intricate interaction networks with diverse biomolecules. Glycocalyx-editing techniques offer potent tools to probe their functions. In this study, we devised a HaloTag-based technique for glycan manipulation, which enables the introduction of chemically synthesized glycans onto a specific protein (protein of interest, POI) and concurrently incorporates fluorescent units to attach homogeneous, well-defined glycans to the fluorescence-labeled POIs. Leveraging this HaloTag-based glycan-display system, we investigated the influence of the interactions between Gal-3 and various N-glycans on protein dynamics. Our analyses revealed that glycosylation modulates the lateral diffusion of the membrane proteins in a structure-dependent manner through interaction with Gal-3, particularly in the context of the Gal-3-induced formation of the glycan network (galectin lattice). Furthermore, N-glycan attachment was also revealed to have a significant impact on the extracellular vesicle-loading of membrane proteins. Notably, our POI-specific glycan introduction does not disrupt intact glycan structures, thereby enabling a functional analysis of glycans in the presence of native glycan networks. This approach complements conventional glycan-editing methods and provides a means for uncovering the molecular underpinnings of glycan functions on the cell surface.

Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.

PURPOSE: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. METHODS: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. RESULTS: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6-82.7 mm). In the full analysis set, the adjusted mean change in VAS was - 22.07 and - 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was - 2.99 mm (95% confidence interval [CI] - 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. CONCLUSION: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. CLINICAL TRIAL REGISTRATION: JapicCTI-184143/jRCT2080224082 (October 5, 2018).

Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma.

Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.

IgG4 related lung disease mimicking multiple pleural disseminated lung cancer.

IgG4-related lung disease (IgG4-RLD) can present with various types of radiological findings such as nodule, ground-glass opacity, alveolar interstitial, and bronchovascular involvement. IgG4-RLD generally manifests as mild clinical symptoms, despite evidence from the image findings. Herein we report an asymptomatic patient with IgG4-RLD mimicking multiple pleural disseminated lung cancer.

[Clinical Features in Surgical Cases of Female Spontaneous Pneumothorax;Comparison with Male Patients].

We assessed the clinical features in surgery cases of female spontaneous pneumothorax by comparing them with male patients. One hundred six patients ( female/male:16/90)who had undergone surgery for spontaneous pneumothorax between January 2003 and August 2013 was retrospectively studied. Patient background, pneumothorax classification and treatment were assessed. No significant difference was found in patient background and treatment. In pneumothorax classification, the frequency of secondary pneumothorax in females was significantly greater than that in males (p<0.001). Additionally, in females, the number of bulla identified during surgery was significantly fewer and the number of recurrences before surgery was more frequent than that in males.

Intraductal tubulopapillary neoplasm of the pancreas presenting as recurrent acute pancreatitis: A case report.

INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging. PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis. He was admitted to our hospital with severe acute pancreatitis and cholangitis due to intrapancreatic bile duct stenosis. After the treatment of cholangitis, contrast-enhanced computed tomography revealed a tumor at the pancreatic head. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the main pancreatic duct and distal bile duct, and adenocarcinoma was detected using brush cytology of the bile duct stricture and pancreatic juice. The patient was diagnosed with invasive ductal carcinoma and pancreaticoduodenectomy was performed. Histopathological findings revealed dilation of the pancreatic duct, and proliferation of columnar cells and cuboid epithelial cells in the main pancreatic duct of the pancreatic head. Mucus production was poor, and immunostaining results revealed ITPN. The patient is alive and do not exhibit signs of recurrence for 12 months. DISCUSSION: ITPNs can cause acute pancreatitis, which can be challenging to preoperatively diagnose. ITPNs presenting as acute pancreatitis are rare, with reported only 5 cases. CONCLUSION: It is important to be keep in mind that there is a possibility of ITPN after diagnosis of idiopathic acute pancreatitis.

Convergent Synthesis of a Bisecting N-Acetylglucosamine (GlcNAc)-Containing N-Glycan.

The chemical synthesis of a bisecting N-acetylglucosamine (GlcNAc)-containing N-glycan was achieved by a convergent synthetic route through [4+2] and [6+2] glycosylations. This synthetic route reduced the number of reaction steps, although the key glycosylations were challenging in terms of yields and selectivities owing to steric hindrance at the glycosylation site and a lack of neighboring group participation. The yields of these glycosylations were enhanced by stabilizing the oxocarbenium ion intermediate through ether coordination. Glycosyl donor protecting groups were explored in an effort to realize perfect α selectivity by manipulating remote participation. The simultaneous glycosylations of a tetrasaccharide with two disaccharides was investigated to efficiently construct a bisecting GlcNAc-containing N-glycan.

Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal Surgical Skills in a General Hospital.

OBJECTIVE: We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital. MATERIALS AND METHODS: A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19). RESULTS: Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon. CONCLUSIONS: Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.

Spontaneous regression of transverse colon cancer: a case report.

Spontaneous regression (SR) of many malignant tumors has been well documented, with an approximate incidence of one per 60,000-100,000 cancer patients. However, SR of colorectal cancer (CRC) is very rare, accounting for less than 2% of such cases. We report a case of SR of transverse colon cancer in an 80-year-old man undergoing outpatient follow-up after surgical treatment of early gastric cancer. Colonoscopy (CS) revealed a Borrmann type II tumor in the transverse colon measuring 30 × 30 mm. Because the patient underwent anticoagulant therapy, we did not perform a biopsy at that time. A second CS was performed 1 week after the initial examination and revealed tumor shrinkage to a diameter of 20 mm and a shift to the Borrmann type III morphology. Biopsy revealed a poorly differentiated adenocarcinoma. One week after the second CS, we performed a partial resection of the transverse colon and D2 lymph node dissection. Histopathology revealed inflammatory cell infiltration and fibrosis from the submucosal to muscularis propria layers in the absence of cancer cells, leading to pathological staging of pStage 0 (T0N0). The patient had an uneventful recovery, and CS performed at 5 months postoperatively revealed the absence of a tumor in the colon and rectum. The patient continues to be followed up as an outpatient at 12 months postoperatively, and no recurrence has been observed.

Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas.

In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

Clear cell sarcoma of the esophagus: report of a case.

We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for α-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus.

Asymmetric Mannich reaction of α-keto imines catalyzed by diarylprolinol silyl ether.

Synthetic methods: An asymmetric catalytic, desulfonylative Mannich reaction of α-keto imines with aldehydes, as catalyzed by diarylprolinol silyl ether 1, was developed. It gave the Mannich product in good yield with excellent anti and enantioselectivity (see scheme; Boc = tert-butoxycarbonyl, TMS = trimethylsilyl).

[Prognostic factors affecting the surgical treatment of metastatic lung tumor from colorectal cancer].

For aging, people having malignant disease are increasing. And surgical resection is an important part in the treatment of pulmonary metastasis from colorectal cancer. We analyzed the treatment outcome and prognostic factors affecting survival in our subset of patients. We have experienced 64 operations of metastatic lung tumors from colorectal cancer for 23 years since January 1988. Various factors affecting prognosis are studied based on 5-year survival in this report. Overall 5-year survival rate was 38.7%. The disease-free intervals more than 2 years, a solitary metastatic pulmonary lesion and the serum level of prethoracotomy carcinoembryonic antigen (CEA) were significantly affecting factors on the prognosis. Furthermore, sequential study for 23 years couldn't demonstrate the prognostic improvement by the advance of the thoracoscopic technology or the development of the new anti-cancer drugs, though the treatment of patients with pulmonary metastases from colorectal cancer continues to evolve. The role of pulmonary metastasectomy is very important to reduce the volume of metastatic lesions for the better prognosis.

[Pulmonary pleomorphic carcinoma with rapid growth causing death in a short period after surgery; report of a case].

Pleomorphic carcinoma is rare in the primary lung cancer with a poor prognosis. We reported a resected case of pleomorphic carcinoma of the lung with rapid progression. A 62-year-old male with a tumor shadow in the right lung which had not been noted 9 months before was referred to our hospital. The abnormal shadow was not noted 9 months ago. The tumor located in the right lower lobe and rapidly enlarged from 7.5 cm to 9.5 cm in a month. Right pneumonectomy was necessary, because of the intrapulmonary metastasis in the right upper lobe. Pathological findings showing spindle cells with massive necrosis, were consistent with a diagnosis of pleomorphic carcinoma. Only by 45 days after operation, local recurrence and metastases to the brain, right adrenal gland and small intestine were found, resulting in death at 67 days after operation.

Pancreatoduodenectomy for circumportal pancreas accompanying the retroportal pancreatic duct: a case report and review of the literature.

Circumportal pancreas (CP) is an extremely rare pancreatic fusion anomaly which is usually asymptomatic. This report presents the case of a patient with a tumor in the head of a CP and the retroportal accessory pancreatic duct in the pancreatic tissue behind the portal vein. A 53-year-old male was diagnosed with a nonfunctioning neuroendocrine tumor of the pancreas and resection of the tumor was scheduled. The patient was revealed to have CP on preoperative computed tomography and endoscopic retrograde cholangiopancreatography, which showed the pancreatic tissue encircling the portal vein and the retroportal accessory pancreatic duct. The patient safely underwent pylorus-preserving pancreatoduodenectomy reconstructed with pancreaticogastrostomy.

[Two cases of neuroendocrine carcinoma of the rectum].

We report two cases of neuroendocrine carcinoma of the rectum. CASE 1: A 50s woman was diagnosed as rectal cancer and underwent anterior resection of the rectum and lymphnode dissection. The histological diagnosis was neuroendocrine carcinoma with peritoneal dissemination. She was treated with chemotherapy as an outpatient. One year later from the operation, multiple liver metastases were revealed and she died eight months later. CASE 2: A 50s man underwent endoscopic mucosal resection (EMR) of the rectum as rectal tumor and histological diagnosis was an early well-moderate deferenciated carcinoma and its cut-tend was unclear. He received a careful follow-up. One year later, a follow-up colonoscopy revealed a submucosal tumor in the lower rectum. He was diagnosised with local reccurence of rectal cancer, and then underwent an abdominoperineal resection of the rectum and lymphnode dissection. The histological diagnosis was poorly differenciated neuroendocrine carcinoma with lymphnode metastasis. Two months later from the operation, a local reccurence was revealed and he was treated with octreotide and irradiation.

[A case of AFP-producing gastric cancer patient with liver relapse occurred three months after endoscopic mucosal resection (EMR) and gastrectomy].

A 60s male was admitted to our hospital for a diagnosis of gastric tumor sized 20 mm in diameter at the fornix of the stomach. Endoscopic mucosal resection (EMR) was performed, and the resected tumor was pap, m, ly0, v0, HMX, VM0, pathologically. One month after the EMR, the local recurrence was confirmed and a partial gastrectomy was performed. Pathological findings were tub1, sm2, ly1, v1, HM0, VM0. Total gastrectomy was added because of the possibility of the lymph node metastasis. Pathological findings revealed no residual cancers. The final pathological diagnosis was T1b(sm2) N0H0P0M0, Stage IA, based on the Japanese classification of gastric cancer. Three months thereafter, CT showed multiple liver metastases. Immunohistochemical study of the operated tumor revealed AFP-producing gastric cancer. Chemotherapy was performed, but he died of the gastric cancer. Endoscopic treatment is a minimally invasive therapeutic strategy, but it requires a considerable care in application.

[A case of metastasis to the stomach from primary adenocarcinoma of the lung cancer].

We report a case of gastric metastasis of lung cancer performed gastrectomy for the primary foci. A 70s woman was diagnosed as having right lung cancer and underwent right lower lobectomy and lymph node dissection. The histological diagnosis was adenocarcinoma (pT4, N2, M0). Four years later, positron emission tomography (PET)-CT revealed a tumor in the stomach and para-aortic lymph nodes swelling. The submucosal tumor was showed in the cardia by endoscopic examination. Biopsy showed a papillary adenocarcinoma. With the diagnosis of gastric metastasis from lung cancer, she was operated on. A proximal gastrectomy was carried out. The histopathological examination demonstrated papillary adenocarcinoma similar to that of the lung cancer with lymph node metastasis. No postoperative complications occurred and she was discharged from the hospital. Since then, she was treated with adjuvant chemotherapy as an outpatient.

[Two cases of gastric endocrine cell carcinoma].

Gastric endocrine cell carcinoma is rare and associated with a poor prognosis. The first case was a man in his sixties with gastric endocrine cell carcinoma, of which a clinical finding was T2N1M0H1 (Stage IV). S-1 + CDDP therapy was selected and failed. CDDP+CPT-11 therapy was started and CT showed a partial response in ten months. But the tumor was re-grown and the patient died twenty months after diagnosis. The second case was a man in his seventies with gastric endocrine cell carcinoma, of which a clinical finding was T3N1M0H0P0, Stage IIIa, underwent total gastrectomy. Abdominal contrast-enhanced CT scan performed a month after the operation disclosed hepatic metastasis. After two months of S-1 regimen, CDDP + CPT-11 therapy was started.