Multicellular structures in thin free liquid films induced by thermocapillary effect.

HYPOTHESIS: Multicellular convective structures that are induced in a fluid exposed to temperature difference are commonly observed in nature and in daily life. Different types of basic flow patterns are induced in a free liquid film by thermocapillary effect, whereas the formation of such multicellular structures has not been hitherto unravelled. EXPERIMENTS: A thin film of high-Prandtl-number liquid is prepared in a rectangular aperture of the order of 0.1 mm in thickness sustained by its surface tension. A designated temperature difference is imposed between the end surfaces of the aperture to generate a thermocapillary-driven convection in the free liquid film. We monitor the induced thermal flow patterns to evaluate the cell numbers and their wavelength by experimental and numerical approaches. FINDINGS: The multicellular structure is established by the thermocapillary effect in the free liquid films. The cell number increases in a stepwise manner as the liquid-film width increases. When the cell number increases, another pair of the cells always newly emerges. We determine the wavelength in a non-dimensional manner, and present the variation of the wavelength against the aspect ratio corresponding to the liquid-film width. The results are compared to those of convectional Marangoni-Bénard convection.

Thermal Stability Changes in Telomeric G-Quadruplex Structures Due to N6-Methyladenine Modification.

N6-methyladenine modification (m6dA) has recently been identified in eukaryote genomic DNA. The methylation destabilizes the duplex structure when the adenine forms a Watson-Crick base pair, whereas the methylation on a terminal unpaired adenine stabilizes the duplex structure by increasing the stacking interaction. In this study, the effects of m6dA modification on the thermal stability of four distinct telomeric G-quadruplex (G4) structures were investigated. The m6dA-modified telomeric oligonucleotide d[AGGG(TTAGGG)3] that forms a basket-type G4 in Na+, d[(TTAGGG)4TT] that forms a hybrid-type G4 in K+ (Form-2), d[AAAGGG(TTAGGG)3AA] that forms a hybrid-type G4 in K+ (Form-1), and d[GGG(TTAGGG)3T] that forms a basket-type G4 with two G-tetrads in K+ (Form-3) were analyzed. Circular dichroism melting analysis demonstrated that (1) A7- and A19-methylation destabilized the basket-type G4 structure that formed in Na+, whereas A13-methylation stabilized the structure; (2) A15-methylation stabilized the Form-2 G4 structure; (3) A15- and A21-methylations stabilized the Form-1 G4 structure; and (4) A12-methylation stabilized the Form-3 G4 structure. These results suggest that m6dA modifications may affect the thermal stability of human telomeric G4 structures in regulating the biological functions.

[A Case of Pancreaticoduodenectomy for Vater Papillary Cancer with Celiac Axis Stricture].

During the follow‒up of Vater papillary adenoma, a 74‒year‒old man was admitted to our hospital with a chief complaint of upper abdominal pain and diagnosed as cholangitis with obstructive jaundice. Cholestasis had been considered to be caused by papillary adenoma, however, EUS exam showed continuous bile duct wall irregularity from papilla of Vater. So we diagnosed as papillary carcinoma with extension to the distal bile duct. Preoperative CT showed the stenosis at the root of celiac artery, and hepatic blood flow was considered to be supplied via the pancreatic head arcade from superior mesenteric artery, so an anastomosis of gastroduodenal artery and inferior pancreaticoduodenal artery was performed during pancreaticoduodenectomy( PD). Like this case, when performing PD with celiac artery stricture, it is important to evaluate hepatic blood flow before and during surgery and prepare for the arterial reconstruction.

[Analysis of 16 Cases of Primary Duodenal Carcinoma in Our Hospital].

Primary duodenal carcinoma is a rare disease among gastrointestinal malignancies and has little evidence. We evaluated retrospectively the treatment status of 16 cases of primary duodenal carcinoma in our hospital between 2010 and 2019. The median age was 72(58-88)years and 63% of patients were male, and Each stage were Stage 0 in 4 cases, Stage Ⅰ in 1 case, Stage ⅢA in 2 cases, Stage ⅢB in 3 cases, and Stage Ⅳ in 6 cases(UICC 8th edition). Initial treatment was endoscopic therapy in 3 cases, surgery in 10 cases, chemotherapy in 1 case, and best supportive care in 2 case. The 2-year survival rate was 51.3% and the MST was 25.4 months in all cases. The Stage 0, Stage Ⅰ cases had all recurrence-free survival, while the Stage ⅢA or higher cases, 2-year survival rate was 33.8% and the MST was 20.0 months. Also, XELOX was often selected as the first-line treatment for chemotherapy regimens including recurrence treatment.

[Case of Gastric Cancer with Para-Aortic Lymph Node Metastases Successfully Treated with S-1/Docetaxel Chemotherapy].

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

[A Long-Survived Case of Gastric Cancer with Multiple Liver Metastases Who Underwent Gastrectomy and Received Chemotherapy].

A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.

[Case Series of the TAS-102 plus Bevacizumab(Bev)Combination Therapy in Unresectable Advanced Colorectal Cancer].

A phase-Ⅱtrial of TAS-102 plus bevacizumab(Bev)combination therapy showed a progression-free survival(PFS)of 3.7-4.6 months. Here, we report 12 cases of unresectable advanced recurrent colorectal cancer treated with TAS-102 plus Bev therapy at our hospital between June 2017 and February 2020. The median PFS was 6 months(2-12). Adverse events greater than Grade 3 were neutropenia(33.3%), febrile neutropenia(8.3%), thrombocytopenia(8.3%), and vomiting (8.3%). The frequency of non-hematotoxicity was low. In conclusion, the TAS-102 plus Bev therapy may be a useful option for the late-line treatment of unresectable advanced recurrent colorectal cancer.

[Launching Robot-Assisted Laparoscopic Surgery for Rectal Cancer in Our Hospital-Short-Term Results].

Robot-assisted laparoscopic surgery(RALS)for rectal cancer has been covered by National Health Insurance in Japan since April 2018. We launched RALS in our hospital in October 2019 and now report the short-term results(up to January 2020). Altogether, 15 consecutive patients(12 men, 3 women: median age 70 years)with rectal cancer underwent RALS during that period. For the first 2 cases, we performed RALS under the instruction of an experienced proctor from another institution. Among the 15 patients, 6 underwent high anterior resection and 9 low anterior resection. Median operating time was 358 min, median intraoperative blood loss was 0 mL, and there were no apparent intraoperative complications. Median postoperative length of hospital stay was 13 days, and only 1 patient developed a high-grade complication(Clavien-Dindo Grade Ⅲb)postoperatively. Hence, RALS for rectal cancer was launched successfully in our institution.

[A Case Report of Hepatocellular Carcinoma with Complete Spontaneous Regression].

This is the case of a 77-year-old man with hepatitis C. AFP was increased by 95.9 ng/mL, and abdominal computed tomography(CT)revealed a 20 mm mass in the S6 segment of the liver. Therefore, the patient was referred to our hospital for further examination. Abdominal echo at our hospital showed a 10 mm, low echoic lesion in S6, which tended to shrink. Similarly, CT showed a low-concentration nodule of 10 mm in S6, but the contrast effect in the arterial phase was not clear. EOB-MRI showed a 10 mm nodule of DWI hyperintensity and hepatocyte phase hypointensity in S6. Based on these, a diagnosis of hepatocellular carcinoma(T1N0M0, StageⅠ)was made, and we decided to perform surgery. Intraoperative findings showed no tumor on the liver surface, and echo did not reveal a reproducible nodule. The tumor site was estimated using a 3-dimensional image analysis system created preoperatively. Laparoscopic partial resection of the liver S6 segment was performed at a position distant from the estimated tumor site. Rapid pathological examination showed no malignant findings, but no significant lesion was found in the residual liver, and the surgery was completed. The postoperative pathological diagnosis revealed no clear tumor. EOB-MRI was performed again postoperatively, but no tumor was found in the residual liver. The tumor site that had been indicated preoperatively was resected, and we hypothesized that the hepatocellular carcinoma had spontaneously regressed. Although several mechanisms have been reported for the spontaneous regression of hepatocellular carcinoma, few cases of spontaneous regression during surgery have been reported. We do not have a definite opinion on the treatment protocol for hepatocellular carcinoma that regresses spontaneously; therefore, we will report on past cases.

[Adjuvant Chemotherapy and the Prognosis of ypStageâ Gastric Cancer].

The efficacy of postoperative chemotherapy for patients with ypStageⅠgastric cancer has not been evaluated. We investigated the characteristics and prognosis of7 patients with ypStage Ⅰgastric cancer. cStages were ⅡA, ⅡB, ⅢB, and Ⅳin 1, 1, 1, and 4 patients, respectively. S-1 plus cisplatin and docetaxel plus cisplatin plus S-1 were administered in 5 and 2 patients, respectively, for 2-8 courses before gastrectomy. Microscopic curative resection was performed for all patients. ypStage was 0, ⅠA, and ⅠB in 1, 2, and 4 patients. All patients received postoperative chemotherapy with S-1 or docetaxel plus S-1(DS). The 5-year recurrence-free survival was 71% and the 5-year overall survival was 68%. Two patients developed recurrence. One patient developed recurrence 1 year and 1 month after gastrectomy in spite of S-1 treatment for 4 months. Another patient developed recurrence 11 months after gastrectomy after DS treatment for 4 months followed by S-1. The other 5 patients received S-1 for 1-5 years and have survived without recurrence. Although the prognosis ofypStage Ⅰgastric cancer was comparatively good, the regimen and courses ofpostoperative chemotherapy should be evaluated in a prospective study.

[Two Cases of Liver Metastasis from Gastric Cancer Achieving Long-Term Survival Successfully Treated with Stereotactic Body Radiotherapy(SBRT)].

We report 2 cases with long-term survival following stereotactic body radiotherapy(SBRT)for liver metastasis from gastric cancer. Case 1 was a 65-year-old man. We performed distal gastrectomy for gastric cancer with liver metastasis prior to chemotherapy due to pyloric stenosis. Postoperative S-1 chemotherapy was administered. Two liver metastases observed before the operation were temporarily reduced in size but subsequently enlarged; therefore, SBRT was performed 13 months postoperatively. The liver metastases showed a complete response(CR)and the patient is alive 4 years and 11 months after SBRT(6 years postoperatively). Case 2 was a 71-year-old woman. After performing distal gastrectomy, liver metastasis emerged during postoperative S-1 adjuvant chemotherapy; therefore, SBRT was performed 11 months postoperatively. She was then administered weekly paclitaxel. However, she underwent a right hepatic lobectomy 13 months after SBRT for suspected remnant or marginal recurrence by abdominal enhanced CT. Histopathological examination showed that the tumors contained fibrotic connective tissue with no viable cancer cell remnants; therefore, the therapeutic effect was determined to be of Grade 3. The patient is alive without recurrence in the remnant liver 4 years and 7 months after SBRT(5 years and 6 months after the operation of gastric cancer). Thus, SBRT for liver metastasis from gastric cancer may be considered an effective local treatment.

[A Case Report of Long Survival in Pancreatic Cancer with Superior Mesenteric Arterial Invasion Following Multimodal Therapy].

The prognosis of pancreatic cancer with superior mesenteric arterial invasion is very poor and judgment of surgical indication is very difficult. We report a case that received multimodal therapy for pancreatic cancer with superior mesenteric arterial invasion. A 43-year-old woman consulted a local doctor because of upper abdominal pain. Ultrasonography revealed a nodule in the pancreatic body and elevated CA19-9 values. She was referred to our hospital for evaluation and therapy. Computed tomography showed a low-density area in the pancreatic body and around the superior mesenteric artery. The clinical diagnosis was pancreatic cancer with superior mesenteric arterial invasion. She received chemoradiation therapy(RT, 50.4 Gy, gemcitabine[GEM]plus TS-1)followed by distal pancreatectomy. She received adjuvant chemotherapy(TS-1)for 6 months. However, follow-up CTperformed 10 months after surgery revealed local recurrence. The patient received chemotherapy( GEM)for 8 months and GEM plus nab-PTX for 22 months. She died from the cancer 50 months after the primary operation.

[A Case Report of Advanced Gastric Cancer with Synchronous Liver Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

Gastroscopy ofa 79-year-old man complaining ofanemia showed a type 3 tumor at the lesser curvature ofthe gastric body. A biopsy revealed poorly differentiated HER2-negative adenocarcinoma. Abdominal CT showed the tumor at the lesser curvature ofthe gastric body, multiple lymph nodes with a maximum diameter of 25mm at the lesser curvature, and a mass measuring 50mm with ring enhancement on S6 ofthe liver. The clinical diagnosis was cT4aN2M1(Hep), cStage Ⅳ. He was treated with chemotherapy comprising 4 courses ofS -1 plus oxaliplatin. Although the tumor had shrunk remarkably, chemotherapy was discontinued because of anorexia. Therefore, we performed total gastrectomy and hepatic partial resection(S6). The final staging was ypT3N0M0, ypStage ⅡA. We achieved R0 resection, and he has shown no recurrence without adjuvant chemotherapy for 3 years.

[A Case of Chemotherapy with Abscess Drainage for Pancreatic Cancer Detected Due to Peritonitis].

A 69-year-old woman was admitted to our hospital because of abdominal pain. Abdominal CT revealed free air, so we performed an emergency operation. Although the perforation site could not be confirmed, pancreatic cancer invading the stomach, spleen, and transverse colon was found. As a splenic abscess and peritoneal dissemination were also found, we created a colostomy and placed drains. Although the postoperative course was good, the splenic abscess continuous with the tumor remained. We thought that early removal of the drain would be difficult, so chemotherapy was introduced while continuing drainage. Fortunately, the pancreatic cancer was controlled, and the abscess tended to shrink, so we removed the tube 137 days after the surgery. After that, we continued chemotherapy, but in the second year after the surgery, the liver metastasis acutely exacerbated and DIC also developed, resulting in cancer death. If surgical intervention is difficult, as in this case, chemotherapy may be considered as an option, keeping in mind the possibility of exacerbation of infection.

[A Case of Gastric Cancer with Ramucirumab-Related Colon Perforation after a Subtotal Colectomy].

A 61-year-old man with advanced gastric cancer underwent distal gastrectomy after chemotherapy. Fifteen months later, peritoneal metastasis and colon stenosis were detected. Therefore, subtotal colectomy and ileosigmoidostomy were performed. Three weeks later, paclitaxel(PTX)treatment was initiated, followed by nab-PTX with ramucirumab(Ram)treatment at 7 weeks postoperatively. The patient experienced sudden abdominal pain diagnosed as gastrointestinal perforation 13 weeks postoperatively. Operative findings showed that the anastomosis of the ileosigmoidostomy was perforated, and this was treated using sutures. Angiogenesis inhibitors should be carefully administered even 4 weeks or more after surgery.

[A Case of Esophagogastric Junction Adenocarcinoma with Multiple Esophageal Intramural Metastases].

We experienced a case of multiple esophageal intramural metastasis from adenocarcinoma of the esophagogastric junction. A 58-year-old man was admitted complaining of dysphagia. Upper gastrointestinal endoscopy revealed a type 3 tumor at the esophagogastric junction. Biopsy showed Group 5, poorly differentiated adenocarcinoma. Abdominal CT indicated regional and para-aortic lymph node metastasis. Then the clinical diagnosis was established as Siewert type Ⅲ adenocarcinoma and cT4aN2M1(LYM), cStage Ⅳ. After conducting 4 courses of SP(S-1/cisplatin)therapy, endoscopy showed partial response of the primary tumor and the submucosal nodules in the lower esophagus. We performed lower esophagectomy and total gastrectomy by left thoracotomy and laparotomy. Six esophageal nodules were identified in the lower esophagus, and pathological examination proved the poorly differentiated adenocarcinoma. The esophageal tumors were diagnosed as intramural metastases. The patient showed hepatic and lymphatic recurrence 9 months after surgery, and died 15 months after surgery. Esophageal intramural metastasis from esophagogastric junction adenocarcinoma is relatively rare. We discuss this case along with a review of the literature.

[A Case of Peritoneal Dissemination of Hepatocellular Carcinoma after Laparoscopic Hepatectomy].

A 69-year-old man was found to have a hepatocellular carcinoma of 2.3 cm in diameter, with extrahepatic growth in liver S4 during follow-up for chronic hepatitis C and liver cirrhosis. We performed a laparoscopic partial liver resection, but the tumor capsule was injured by the retractor used to keep the working space at the bleeding site. The pathological diagnosis was moderately differentiated hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). 7 months after the surgery, intrahepatic reoccurrence appeared. Thus, transcatheter arterial chemoembolization(TACE)and radiofrequency ablation were performed. However, a single recurrence ofperitoneal dissemination appeared 8 months after the reoperation. We selected laparoscopic operation this time. Intraperitoneally, we found 4 peritoneal disseminated lesions and resected all the lesions macroscopically. However, even after the resection, peritoneal dissemination recurred and increased. Therefore, we continued treatment with sorafenib and S-1 as systemic therapy, TACE and transcatheter arterial infusion(TAI)for the multiple recurrences in the liver, and radiotherapy for the peritoneal dissemination focuses. However, his general condition worsened, and liver failure occurred. Thus, he was shifted to complete palliative treatment and died 2 years 6 months after the initial operation. The recurrent form ofhepatocellular carcinoma is mainly an intrahepatic recurrence, and recurrence ofperitoneal dissemination is rare. In this case, the intraoperative operation was considered to be the possible cause ofthe recurrence.

[A Case of Urothelial Carcinoma Who Underwent Pancreaticoduodenectomy and Was Diagnosed with Groove Pancreatitis and Preoperatively Suffered from Duodenal Stenosis].

We report a case of a highly advanced urothelial carcinoma accompanied by duodenal stenosis with pancreaticoduodenectomy. A6 6-year-old man presented with upper abdominal pain and vomiting. Acute pancreatitis and hydronephrosis were diagnosed with urgent hospitalization, but jaundice appeared, and stenosis of the duodenum was also found. Thus, we suspected groove pancreatitis or pancreatic cancer, and performed pancreaticoduodenectomy. However, poorly differentiated adenocarcinoma was observed in the retroperitoneal dissection surface in the intraoperative rapid tissue and right hemicolectomy, right nephrectomy, and right ureteral resection were added to the diagnosis. The final diagnosis was urothelial carcinoma. GEM plus CBDCAtherapy was administered as adjuvant chemotherapy. However, obstructive jaundice, acute cholangitis, and acute pancreatitis developed due to occlusion of the intestine due to local recurrence 4 months after surgery. We attempted to reduce yellowing by PTCD; perforation of the small intestine also occurred and a drainage tube was placed in the abdominal cavity. Although a lull condition was obtained, intestinal obstruction due to cancer peritonitis worsened and the patient died 8 months after the operation. In this case, there was no hematuria before surgery and cytology results of urine were negative, so a diagnosis of urinary tract cancer was difficult. There was no report of duodenal stenosis due to urothelial carcinoma.

α-1,6-Fucosyltransferase (FUT8) inhibits hemoglobin production during differentiation of murine and K562 human erythroleukemia cells.

Erythropoiesis results from a complex combination of the expression of several transcription factor genes and cytokine signaling. However, the overall view of erythroid differentiation remains unclear. First, we screened for erythroid differentiation-related genes by comparing the expression profiles of high differentiation-inducible and low differentiation-inducible murine erythroleukemia cells. We identified that overexpression of α-1,6-fucosyltransferase (Fut8) inhibits hemoglobin production. FUT8 catalyzes the transfer of a fucose residue to N-linked oligosaccharides on glycoproteins via an α-1,6 linkage, leading to core fucosylation in mammals. Expression of Fut8 was down-regulated during chemically induced differentiation of murine erythroleukemia cells. Additionally, expression of Fut8 was positively regulated by c-Myc and c-Myb, which are known as suppressors of erythroid differentiation. Second, we found that FUT8 is the only fucosyltransferase family member that inhibits hemoglobin production. Functional analysis of FUT8 revealed that the donor substrate-binding domain and a flexible loop play essential roles in inhibition of hemoglobin production. This result clearly demonstrates that core fucosylation inhibits hemoglobin production. Third, FUT8 also inhibited hemoglobin production of human erythroleukemia K562 cells. Finally, a short hairpin RNA study showed that FUT8 down-regulation induced hemoglobin production and increase of transferrin receptor/glycophorin A-positive cells in human erythroleukemia K562 cells. Our findings define FUT8 as a novel factor for hemoglobin production and demonstrate that core fucosylation plays an important role in erythroid differentiation.