Serial Cultivation of an MSC-Like Cell Line with Enzyme-Free Passaging Using a Microporous Titanium Scaffold.

In vitro studies on adherent cells require a process of passage to dissociate the cells from the culture substrate using enzymes or other chemical agents to maintain cellular activity. However, these proteolytic enzymes have a negative influence on the viability and phenotype of cells. The mesenchymal stem cell (MSC)-like cell line, C3H10T1/2, adhered, migrated, and proliferated to the same extent on newly designed microporous titanium (Ti) membrane and conventional culture dish, and spontaneous transfer to another substrate without enzymatic or chemical dissociation was achieved. The present study pierced a 10 µm-thick pure Ti sheet with 25 µm square holes at 75 µm intervals to create a dense porous structure with biomimetic topography. The pathway of machined holes allowed the cells to access both sides of the membrane frequently. In a culture with Ti membranes stacked above- and below-seeded cells, cell migration between the neighboring membranes was confirmed using the through-holes of the membrane and contact between the membranes as migration routes. Furthermore, the cells on each membrane migrated onto the conventional culture vessel. Therefore, a cell culture system with enzyme-free passaging was developed.

Fluorescence cholangiography for detection of a cystic duct drained into an accessory hepatic duct: A case report.

INTRODUCTION: Laparoscopic cholecystectomy is a safe and standard procedure, but serious bile duct injury may occur due to anatomical anomalies of the biliary tract, especially the accessory hepatic duct. The use of intraoperative fluorescence cholangiography with indocyanine green during laparoscopic cholecystectomy can reportedly prevent bile duct injury. PRESENTATION OF CASE: A 55-year-old woman with upper abdominal pain was referred to our hospital. Laboratory investigations revealed elevated leukocytes and biliary enzymes, while computed tomography demonstrated increased fatty tissue density around the gallbladder. Magnetic resonance cholangiopancreatography and drip infusion cholangiographic-computed tomography showed that the cystic duct drained into an accessory hepatic duct. Due to the diagnosis of cholelithiasis with a biliary anomaly, we performed laparoscopic cholecystectomy using fluorescence cholangiography with indocyanine green. We were able to recognize the accessory hepatic duct and cystic duct, then safely dissect the cystic duct without bile duct injury. DISCUSSION: Laparoscopic cholecystectomy is generally regarded as a safe procedure, but complications and even mortalities can arise in patients with anatomical anomalies of the biliary tract. The aid of intraoperative fluorescence cholangiography with indocyanine green allowed to recognize and identify the accessory hepatic duct and cystic duct, allowing us to operate without injury to the bile duct. CONCLUSIONS: Our experience supports the ease of use, safety, and effectivity of fluorescence cholangiography with indocyanine green. This may become the optimal standard technique to prevent bile duct injury.

Impact of pathological complete response following neoadjuvant chemotherapy (gemcitabine, nab-paclitaxel, S-1) and radiation for borderline resectable pancreatic cancer: a case report and review of literature.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy, even if surgical resection is possible (median survival: < 30 months). The prognosis of borderline resectable pancreatic cancer (BR-PC) is even worse. There is no clear consensus on the optimal treatment strategy, including pre/postoperative therapy, for BR-PC. We report a patient with BR-PC who achieved clinical partial response with neoadjuvant chemoradiation therapy (NACRT) and underwent curative resection, resulting in pathological complete response (pCR). CASE PRESENTATION: A 71-year-old man with jaundice and liver dysfunction was referred to our department because of a 48-mm hypo-vascular mass in the pancreatic head with obstruction of the pancreatic and bile ducts and infiltration of superior mesenteric vein and portal vein. The lesion was identified as atypical cells which suggested adenocarcinoma by biopsy, and he was administered NACRT: gemcitabine and nab-paclitaxel, following S-1 and intensity modulated radiation therapy. After reduction in the tumor size (clinical partial response), pancreaticoduodenectomy was performed, and pCR achieved. Postoperative adjuvant chemotherapy with S-1 was initially administered and the patient is currently alive with no recurrence as of 2 years after surgery. CONCLUSIONS: NACRT is a potentially useful treatment for BR-PC that may lead to pCR and help improve prognosis.

A successful operation for giant intra-abdominal desmoid tumors associated with familial adenomatous polyposis: A case report.

Desmoid tumors are benign proliferations of spindle cells originating in fibro-aponeurotic tissue. Many patients with familial adenomatous polyposis (FAP) die from desmoid tumors, which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. Desmoid tumors are the second most common cause of death in patients with FAP, second to colorectal cancer. Many patients can live a long life with desmoid tumors without symptoms, but when symptoms (ranging from bowel or ureteric obstruction to bowel perforation with abscess and fistula) appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) are valuable in improving the symptoms and controlling the disease. A half-Japanese, half-Caucasian male, who had been diagnosed with intra-abdominal desmoid tumors associated with FAP at age 13, was treated using abdominal wall incision for decompression and chemotherapy from the age of 38. The therapeutic outcome was progressive disease, based on the modified response evaluation criteria in solid tumors (mRECIST), and when he visited our hospital at age 41 the desmoid tumor had invaded the small bowel with a fistula to the abdominal wall. We performed a palliative operation to improve his symptoms, which were fever, abdominal pain, vomiting, and difficulty eating. As the tumor was extremely large and had invaded the small intestine, massive resection including the small intestine was required. To prepare for anticipated massive bleeding, a balloon catheter was placed in the superior mesenteric artery just prior to surgery. Although the operation was extremely difficult, following surgery the patient regained his ability to eat and when discharged was ambulatory and without short-bowel syndrome. We report our experience treating one of the largest reported intraperitoneal desmoid tumors. Resection resulted in a good postoperative course, with improved quality of life and prognosis.

Extracellular Vesicles Derived From Murine Cementoblasts Possess the Potential to Increase Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis.

Cementum resorption, unlike bone resorption, is clinically known to occur only with limited pathological stimuli, such as trauma, orthodontic forces, and large apical periodontitis; however, the molecular mechanisms that control osteoclast formation on the cementum surface remain unclear. In this study, we focused on extracellular vesicles (EVs) secreted by cementoblasts and analyzed their effects on osteoclast differentiation. EVs were extracted from the conditioned medium (CM) of the mouse cementoblast cell line OCCM-30. Transmission electron microscopy (TEM) analysis confirmed the presence of EVs with a diameter of approximately 50-200 nm. The effect of the EVs on osteoclast differentiation was examined using the mouse osteoclast progenitor cell line RAW 264.7 with recombinant receptor activator of nuclear factor (NF)-κB ligand (rRANKL) stimulation. EVs enhanced the formation of tartrate-resistant acid phosphatase (TRAP) activity-positive cells upon rRANKL stimulation. EVs also enhanced the induction of osteoclast-associated gene and protein expression in this condition, as determined by real-time PCR and Western blotting, respectively. On the other hand, no enhancing effect of EVs was observed without rRANKL stimulation. A Western blot analysis revealed no expression of receptor activator of NF-κB ligand (RANKL) in EVs themselves. The effect on rRANKL-induced osteoclast differentiation was examined using the CM of cementoblasts in terms of TRAP activity-positive cell formation and osteoclast-associated gene expression. The conditioned medium partly inhibited rRANKL-induced osteoclast differentiation and almost completely suppressed its enhancing effect by EVs. These results indicate that cementoblasts secreted EVs, which enhanced RANKL-induced osteoclast differentiation, and simultaneously produced soluble factors that neutralized this enhancing effect of EVs, implicating this balance in the regulation of cementum absorption. A more detailed understanding of this crosstalk between cementoblasts and osteoclasts will contribute to the development of new therapies for pathological root resorption.

[A Case of Gallbladder Cancer with Long Survival Treated with Resection after Downstaging with GC Therapy].

A 68-year-old woman with a chief complaint of obstructive jaundice was referred to our hospital. She was diagnosed with gallbladder cancer with invasion to the liver, extrahepatic bile duct, right hepatic artery and portal vein. After endoscopic retrograde biliary drainage, she received chemotherapy with gemcitabine and cisplatin. After 9 courses, the size of the tumor and the lymph nodes decreased, and we planned surgery. There were no unresectable factors, and the right hepatic artery and portal vein were detached from the tumor. We performed a subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection. We then performed adjuvant chemotherapy with S-1 for 1 year. The patient remains alive without recurrence, 5 years after the surgery. We report the case of advanced gallbladder cancer with downstaging after GC therapy.

Mesh repair under the anterior lamina of the rectus sheath (MUAR) for abdominal incisional hernia.

PURPOSE: Abdominal incisional hernia is a frequent complication of major abdominal operations. Our method of performing mesh repair under the anterior lamina of the rectus sheath (MUAR) involves placing mesh between the dorsal surface of the anterior rectus sheath and the rectus abdominis muscle. We evaluated the short-term and long-term outcomes of our MUAR method. METHODS: The subjects of this retrospective study were 80 patients with abdominal incisional hernia, who underwent MUAR at our hospital between August, 2009 and September, 2018. We investigated the rate of recurrence and postoperative complications in these patients, who were followed-up postoperatively for at least 18 months. Patients who completed all visits were then followed-up further with questionnaires. RESULTS: The recurrence rate after MUAR was 0%. Postoperative complications consisted of subcutaneous wound infections in two patients (2.5%), successfully treated with wound cleansing and antibiotics; and subcutaneous hematoma in three patients (3.8%), which was spontaneously absorbed in two patients, and removed in one. There were no other complications, such as seroma, intestinal obstruction, mesh infection and bulging, or prolonged postoperative pain. CONCLUSION: Mesh repair under the anterior lamina of the rectus sheath is simple and safe with positive short-term and long-term outcomes, suggesting that it is a good option for incisional hernia repair.

Evaluation of Preosteoblast MC3T3-E1 Cells Cultured on a Microporous Titanium Membrane Fabricated Using a Precise Mechanical Punching Process.

The surface topography of Titanium (Ti) combined toughness and biocompatibility affects the attachment and migration of cells. Limited information of morphological characteristics, formed by precise machining in micron order, is currently available on the Ti that could promote osteoconduction. In the present study, a pure Ti membrane was pierced with precise 25 µm square holes at 75 µm intervals and appear burrs at the edge of aperture. We defined the surface without burrs as the "Head side" and that with burrs as the "Tail side". The effects of the machining microtopography on the proliferation and differentiation of the preosteoblasts (MC3T3-E1 cells) were investigated. The cells were more likely to migrate to, and accumulate in, the aperture of holes on the head side, but grew uniformly regardless of holes on the tail side. The topography on the both surfaces increased osteopontin gene expression levels. Osteocalcin expression levels were higher on the head side than one on the blank scaffold and tail side (p < 0.05). The osteocalcin protein expression levels were higher on the tail side than on the head side after 21 days of cultivation, and were comparable to the proportion of the calcified area (p < 0.05). These results demonstrate the capacity of a novel microporous Ti membrane fabricated using a precise mechanical punching process to promote cell proliferation and activity.

Mechanical regulation of macrophage function - cyclic tensile force inhibits NLRP3 inflammasome-dependent IL-1ß secretion in murine macrophages.

Mechanical stress maintains tissue homeostasis by regulating many cellular functions including cell proliferation, differentiation, and inflammation and immune responses. In inflammatory microenvironments, macrophages in mechanosensitive tissues receive mechanical signals that regulate various cellular functions and inflammatory responses. Macrophage function is affected by several types of mechanical stress, but the mechanisms by which mechanical signals influence macrophage function in inflammation, such as the regulation of interleukin-1ß by inflammasomes, remain unclear. In this review, we describe the role of mechanical stress in macrophage and monocyte cell function.

Periodontal Regeneration by Allogeneic Transplantation of Adipose Tissue Derived Multi-Lineage Progenitor Stem Cells in vivo.

The ultimate goal of periodontal disease treatment is the reorganization of functional tissue that can regenerate lost periodontal tissue. Regeneration of periodontal tissues is clinically possible by using autogenic transplantation of MSCs. However, autologous MSC transplantation is limited depending on age, systemic disease and tissue quality, thus precluding their clinical application. Therefore, we evaluated the efficacy of allogeneic transplantation of adipose-derived multi-lineage progenitor cells (ADMPC) in a micro-mini pig periodontal defect model. ADMPC were isolated from the greater omentum of micro-mini pigs, and flow cytometry analysis confirmed that the ADMPC expressed MSC markers, including CD44 and CD73. ADMPC exhibited osteogenic, adipogenic and periodontal ligament differentiation capacities in differentiation medium. ADMPC showed high expression of the immune suppressive factors GBP4 and IL1-RA upon treatment with a cytokine cocktail containing interferon-γ, tumor necrosis factor-α and interleukin-6. Allogeneic transplantation of ADMPC in a micro-mini pig periodontal defect model showed significant bone regeneration ability based on bone-morphometric analysis. Moreover, the regeneration ability of ADMPC by allogeneic transplantation was comparable to those of autologous transplantation by histological analysis. These results indicate that ADMPC have immune-modulation capability that can induce periodontal tissue regeneration by allogeneic transplantation.

Effects of rheological properties of rice dough during manufacture of rice cracker on the quality of the end product.

Influence of the viscoelastic properties of rice dough on the mechanical properties and the microstructure of rice crackers was experimentally investigated to predict and control the quality of the rice cracker in the early stage of the lengthy manufacturing process. Various rice doughs steamed for 5, 30, or 60 min and kneaded for 5, 10, or 15 min were examined. Longer steaming and kneading resulted in lower G' and G″ and higher tan δ, specific volume of the rice crackers, decreased nonuniform and deficient network, and thinner cell wall in rice cracker sections. There was a high correlation between tan δ of rice dough and specific volume of the rice cracker samples (R2 > 0.79). The hardness of the rice crackers increased with extending the kneading time for 5 and 30 min as the tan δ increased, while those of the rice crackers made from the rice doughs steamed for 60 min decreased inversely. These results indicated that qualities of rice crackers can be predicted and quantified by measuring viscoelasticity of actual rice doughs during the process. PRACTICAL APPLICATIONS: Improved methods to control quality of end product in manufacturing process and to develop new products with unique textures are desired. We established the new method to quantify the rice dough and this method has already been used for confirming equivalency or improvement of rice dough during manufacture of rice crackers when instrument or condition have changed.

Cyclic Stretch Negatively Regulates IL-1ß Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway.

Macrophages are immune cells of hematopoietic origin that play diverse roles in host defenses and tissue homeostasis. In mechanical microenvironments, macrophages receive mechanical signals that regulate various cellular functions. However, the mechanisms by which mechanical signals influence the phenotype and function of macrophages in the process of inflammation have not yet been elucidated in detail. We herein examined the effects of cyclic stretch (CS) on NLR family, pyrin domain-containing 3 (NLRP3) inflammasome activation in J774.1, a murine macrophage cell line, and mouse primary bone marrow-derived macrophages. We showed that cyclic stretch inhibited adenosine triphosphate (ATP)-stimulated interleukin (IL)-1ß secretion in lipopolysaccharide (LPS)-primed macrophages using ELISA and Western blot analyses. Cyclic stretch did not affect the degradation of the Inhibitor of κB or the nuclear translocation/transcriptional activity of nuclear factor (NF)-κB, suggesting that cyclic stretch-mediated inhibition was independent of the NF-κB signaling pathway. Consistent with these results, cyclic stretch did not affect the LPS-induced expression of inflammasome components, such as pro-IL-1ß and NLRP3, which is known to require the activation of NF-κB signaling. We showed that the cyclic stretch-mediated inhibition of IL-1ß secretion was caused by the suppression of caspase-1 activity. The addition of compound C, a specific inhibitor of adenosine monophosphate-activated protein kinase (AMPK), to LPS-primed macrophages inhibited IL-1ß secretion as well as caspase-1 activation, suggesting that AMPK signaling is involved in ATP-triggered IL-1ß secretion. Furthermore, the phosphorylation of AMPK induced by ATP in LPS-primed macrophages was significantly suppressed by cyclic stretch, indicating that cyclic stretch negatively regulates IL-1ß secretion through the inhibition of caspase-1 activity by attenuating the AMPK pathway. Our results suggest that mechanical stress functions to maintain homeostasis through the prevention of excessive inflammasome activation in macrophages in mechanical microenvironments.

Extracellular calcium increases fibroblast growth factor 2 gene expression via extracellular signal-regulated kinase 1/2 and protein kinase A signaling in mouse dental papilla cells.

We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting. Extracellular Ca2+ increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca2+ sensors, was not detected. Ca2+-mediated Fgf2 expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca2+ increased PKA activity and ERK1/2 phosphorylation. Ca2+-induced PKA activity decreased by pretreatment with PD98059. These findings indicate that elevated extracellular Ca2+ levels led to increased Fgf2 expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.

Extracellular calcium increases fibroblast growth factor 2 gene expression via extracellular signal-regulated kinase 1/2 and protein kinase A signaling in mouse dental papilla cells

Abstract We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). Objective: The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Materials and Methods: Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting. Results: Extracellular Ca2+ increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca2+ sensors, was not detected. Ca2+-mediated Fgf2 expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca2+ increased PKA activity and ERK1/2 phosphorylation. Ca2+-induced PKA activity decreased by pretreatment with PD98059. Conclusions: These findings indicate that elevated extracellular Ca2+ levels led to increased Fgf2 expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.

Effects of intake of Lactobacillus casei subsp. casei 327 on skin conditions: a randomized, double-blind, placebo-controlled, parallel-group study in women.

Lactic acid bacteria are gut flora that play key roles in intestinal homeostasis, which may affect a variety of physiological functions. Our preliminary double-blind, placebo-controlled, parallel-group trials have suggested that intake of heat-killed Lactobacillus casei subsp. casei 327 (designated L. K-1) is effective for improving skin conditions. The aim of this study was to confirm the effect of L. K-1 intake in a randomized, double-blind, placebo-controlled, parallel-group study in healthy female volunteers. Sixty-four subjects were allocated to either the placebo food group (group P, n=32) or active food group (group A, n=32), in which subjects consumed lactobacillus K-1 50 mg (approximately 1 × 1011 bacteria) daily for 8 weeks. After excluding subjects who declined to participate (n=1), violated restrictions (n=4), or were judged ineligible by the principal investigators (n=1), data obtained with 58 subjects (30 in group A and 28 in group P) were analyzed for efficacy by comparing differences from pretrial levels between the two groups. When the level of transepidermal water loss (TEWL) was measured at the arm, the level of TEWL at week 4 of the intake period was significantly lower in group A than group P (p=0.021), suggesting an improvement of skin barrier function. Analysis of skin condition questionnaire data revealed a significant reduction in skin flakiness on the face (week 4). No adverse events were associated with intake of the test foods. The safety of L. K-1 was also confirmed in an independent open-label trial in 11 healthy subjects who consumed excessive amounts of L. K-1 250 mg (approximately 5 × 1011 bacteria). Intake of L. K-1 may therefore be beneficial to skin condition improvement.

Randomized, double-blind, placebo-controlled, parallel-group study of the effect of Lactobacillus paracasei K71 intake on salivary release of secretory immunoglobulin A.

Lactobacillus paracasei K71 was shown to be effective in alleviating the severity of atopic dermatitis in a randomized controlled trial, and a preliminary open-label trial suggested that strain K71 intake enhanced secretory immunoglobulin A (sIgA) release in the saliva. This study investigated the effect of K71 on sIgA release in a randomized, double-blind, placebo-controlled, parallel-group trial. The trial included 62 Japanese subjects aged 20-64 years with relatively low rates of salivary sIgA release. Subjects (n=31 in each group) were randomly given a tablet containing 100 mg (approximately 2 × 1011 bacteria) of K71 or a placebo tablet daily for 12 weeks. After eliminating data for eight subjects (four in each group) who met the exclusion criteria for efficacy analysis, data for 54 subjects were analyzed. The change in the rate of salivary sIgA release 8 weeks after initiation of the study compared with baseline was significantly higher in the K71 tablet group (105.5 ± 119.0 µg/min) than in the placebo group (52.7 ± 62.6 µg/min; p=0.047). There were no adverse events associated with intake of tablets containing K71. The safety of intake of L. paracasei K71 was also confirmed in an independent open-label trial with 20 healthy subjects who consumed excessive amounts of K71-containing food. L. paracasei K71 intake may therefore have some benefits in promoting mucosal immune function.

Analysis of calcium, phosphorus, and carbon concentrations during developmental calcification of dentin and enamel in rat incisors using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX).

OBJECTIVE: The study was designed to investigate the concentrations of calcium (Ca), phosphorus (P), and carbon (C) during developmental calcification of dentin and enamel in rat incisors. METHODS: Mandibular incisors from eight 2-week-old male Wistar rats were analyzed by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). We analyzed data on the elements in the course of developmental processes in dentin and enamel and along the vertical line of the matrix between odontoblasts and ameloblasts. RESULTS: The dentin concentrations of Ca and P and the Ca/P ratio were the lowest, while the C concentration was the highest in initial dentin. The Ca and P concentrations were the lowest, whereas the C concentration was the highest in predentin along the vertical line; the Ca/P ratio did not show any differences. The concentrations of Ca and P increased, while the C concentration decreased during early maturation and more so in late maturation in developing enamel, while the Ca/P ratio increased during late maturation. The Ca and P concentrations and the Ca/P ratio were the highest, while the C concentration was the lowest in enamel adjacent to the junction with dentin on the vertical line. CONCLUSIONS: During tooth development, the initial dentin matrix may possess distinctive mineral characteristics as compared with other parts of dentin and predentin. Elemental composition of the mineral in enamel may change during late maturation. Our results are suggestive of degradation of organic components during developmental calcification in dentin and enamel.

Phase II study of S-1 monotherapy in patients over 75 years of age with advanced gastric cancer (OGSG0404).

BACKGROUND: S-1+cisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients. MATERIALS AND METHODS: Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period. RESULTS: Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths. CONCLUSION: Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function.

[A case of synchronous cancer of the gall bladder, common bile duct, and the papilla of vater].

A 58-year-old man was diagnosed with liver dysfunction during a health exam and subsequently visited a doctor. Abdominal ultrasonography revealed space-occupying lesions in the gall bladder and bile duct, and he was hospitalized for further examination and treatment. Computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiopancreatography (MRCP) revealed double cancer of the gall bladder and bile duct with pancreaticobiliary maljunction (PBM), and we performed a pancreatoduodenectomy. Pathological examination revealed gall bladder and bile duct cancer, and severe dysplasia of the papilla of Vater. We diagnosed synchronous triple cancer because none of the cancers had continuity or vascular invasion. Each cancer was at Stage I, and the patient has survived for 2 years and 6 months without recurrence and no additional treatment. PBM is a mutation of the junction of the pancreatic and bile ducts outside of the duodenal wall, and is a known complication of biliary tract cancer due to the reflux of pancreatic juice and bile. Because K-ras and p53 gene mutations occur in the biliary tract mucosal epithelium, PBM increases the risk of developing multicentric cancer. It is important to consider the existence of double cancer when biliary tract cancer is detected in a PBM patient.

[A case of postpancreaticoduodenectomy local recurrence successfully treated with extended resection].

A 68 -year-old man underwent a pancreaticoduodenectomy after being diagnosed with primary duodenal cancer. The postoperative pathological diagnosis was tub2, SE, ly1, v1, panc3, pn+, N0. Although adjuvant chemotherapy was administered, local recurrence in the portal region was detected 18 months later. The recurrent tumor pressed against the region of the bile duct anastomosis, which caused obstructive jaundice. After serum bilirubin levels were reduced, resection of the recurrent tumors was performed. This required resection of the transverse colon, parts of the portal vein, and the inferior vena cava. The bile duct anastomotic region, which had been infiltrated by the tumor, was excised and rebuilt. The postoperative pathological diagnosis was tub2. The patient continued to receive adjuvant chemotherapy and showed no signs of recurrence 9 months after surgery. Extended resection for local recurrences of primary duodenal cancer may be an effective means of disease control.