[A Case of Recurrent Gallbladder Cancer with a Complete Response to S-1 Alternate-Day Administration].

An 86-year-old woman underwent a cholecystectomy for gallbladder cancer. Seven months later, an abdominal CT scan showed multiple liver and lymph node metastases. Treatment with S-1 was started at a dose of 100 mg/day, but was changed to alternate-day administration because of diarrhea. Metastatic lesions showed a complete response after 7 months of chemotherapy. S-1 alternate-day therapy could be maintained without any severe adverse events. This method can be managed safely and with certainty in an elderly patient and it has demonstrated efficacy in the treatment of recurrent gallbladder cancer.

Proposal of intestinal tissue engineering combined with Bianchi's procedure.

AIM: The aim of this study is to examine the feasibility of the small intestinal submucosa (SIS) when the longitudinal staples during Bianchi's procedure are replaced with SIS graft. METHODS: The mesentery of the bowel was separated based on the bifurcated vessels in five beagles. A 2×7-cm longitudinal half of the bowel was excised and the defect was repaired using SIS with similar blood supply in Bianchi's operation. Six months later, intestinal motility in the SIS-grafted area was recorded. Tissue preparations were obtained from the reorganized area. An organ bath technique with electrical field stimulation was applied. Both the native small intestine and grafted area were morphologically investigated using immunohistochemistry. MAIN RESULTS: All dogs survived and thrived with no anastomotic leakage. Isoperistaltic migrating contractility during fasting was observed through the grafted segment including the reorganized area. The SIS-reorganized tissue contracted in response to an acetylcholine agonist and electrical field stimulation. The mucosa was covered with normal epithelium. Reorganization of neural and smooth muscle cells was observed. CONCLUSIONS: SIS has the potential for use as a scaffold that promotes the formation of a physical and physiological neointestine. Our present proposal approaches a novel surgical treatment in patients with short bowel syndrome.

Catalytic asymmetric diels-alder reaction of quinone imine ketals: a site-divergent approach.

The catalytic asymmetric Diels-Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl-substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels-Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3-alkyl quinone imine ketals from the inherently favored unsubstituted C=C bond to the disfavored alkyl-substituted C=C bond.

Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa.

Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.

Axially chiral dicarboxylic acid catalyzed activation of quinone imine ketals: enantioselective arylation of enecarbamates.

The synthetic utility of quinone imine ketals in the context of asymmetric catalysis was disclosed for the first time. By expanding the utility of chiral Brønsted acid catalysis to the electrophilic activation of quinone imine ketals, we succeeded in the development of highly enantioselective arylation of encarbamates to give α-amino-ß-aryl ethers wherein quinone imine ketals act as functionalized aromatic ring surrogate. Further transformations of the products were also examined to establish procedures to provide chiral ß-aryl amines and α-aryl esters.

Chiral Brønsted acid-catalyzed asymmetric trisubstituted aziridine synthesis using α-diazoacyl oxazolidinones.

Despite the remarkable advances in catalytic asymmetric aziridinations over the past decades, establishing a general procedure for the stereoselective synthesis of trisubstituted aziridines has remained an elusive goal. Chiral N-triflyl phosphoramide-catalyzed reactions of N-α-diazoacyl oxazolidinones and N-Boc imines were developed as a solution to this unmet challenge.

Synthetic application and structural elucidation of axially chiral dicarboxylic acid: asymmetric Mannich-type reaction with diazoacetate, (diazomethyl)phosphonate, and (diazomethyl)sulfone.

The past decade has witnessed the burgeoning research fields of chiral Brønsted acid catalysis. However, carboxylic acids, arguably the most general acids in organic chemistry, have rarely been used as chiral Brønsted acid catalysts. In this context, we developed axially chiral dicarboxylic acid and evaluated its catalytic activity in asymmetric Mannich-type reaction of aromatic aldehyde-derived N-Boc imines and tert-butyl diazoacetate. To demonstrate the remarkable generality of this catalytic system, tert-butyl diazoacetate was replaced with its phosphorus and sulfur analogues, (diazomethyl)phosphonate and (diazomethyl)sulfone, by which synthetically valuable chiral ß-amino phosphonates and ß-amino sulfones could be obtained with high enantioselectivities under identical reaction conditions. X-ray crystallographic analysis of axially chiral dicarboxylic acid complexed with a pyridine derivative revealed its unique internal hydrogen bonding, a property that serves as a basis for its distinctive acidity and chiral scaffold.

Asymmetric trisubstituted aziridination of aldimines and ketimines using n-α-diazoacyl camphorsultams.

The acid-catalyzed reaction of diazoacetates and aldimines (Brookhart-Templeton aziridination) is now recognized as a reliable method to provide enantiomerically enriched disubstituted aziridines, thus owing to the development of asymmetric catalysis. However, the extension of this method to prepare trisubstituted aziridines has not been explored to date, even for racemic products. In this context, and considering their synthetic importance and lack of alternative direct synthetic methods, we recently launched a program to realize this unmet challenge. Herein, we report a detailed study, which led to the establishment of a highly stereoselective synthesis for various trisubstituted aziridines, building on the use of N-α-diazoacyl camphorsultams as a key component.

Stereoselective synthesis of trisubstituted aziridines with N-alpha-diazoacyl camphorsultam.

A Brønsted acid-catalyzed reaction of alpha-substituted alpha-diazocarbonyl compounds bearing camphorsultam as a chiral auxiliary and N-alkoxycarbonyl imines was implemented as an unprecedented means to provide trisubstituted aziridines in a highly stereodefined manner.

Catalytic enantioselective 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with alpha,beta-unsaturated aldehydes.

A yet-unexploited class of azomethine imines, C,N-cyclic azomethine imines, could be successfully employed in highly enantioselective 1,3-dipolar cycloaddition with enals catalyzed by titanium-BINOLate to give pharmaceutically attractive tetrahydroisoquinoline and piperidine motifs.

In vivo motility evaluation of the grafted gastric wall with small intestinal submucosa.

Small intestinal submucosa (SIS) is a bioscaffold that has been showing encouraging results with appropriate tissue regeneration in the gastrointestinal tract. We investigated SIS-induced muscle contractility in vivo and in vitro to determine whether the SIS-grafted area would become physiologically functional in the long term. A 1 cm circular, full-thickness defect was created in a rodent stomach and was repaired using SIS. After 1 year, gastric motility in the SIS-grafted area was recorded in awake animals using a telemetric force transducer system. Muscle was obtained from the same area where in vivo motility had been explored. Organ bath technique with electrical field stimulation was applied. Native stomach and grafts were investigated for morphology by histologic and immunohistochemical analyses. Gastric motility during fasting was enhanced by both food intake and a cholinergic agonist. A muscarinic receptor antagonist inhibited postprandial gastric motility. Responses in vivo were equivalent in grafted versus control rats. The in vitro study revealed that the distribution of muscle and nerves in SIS-regenerated tissue would be proportional to that in normal tissue. Smooth muscle, peripheral nerve, and gastric parietal cells were observed in the SIS-regenerated wall. SIS has the potential to promote a physical and physiological regeneration with intrinsic nerve migration.

[A case of ascending colon cancer successfully treated for synchronous liver metastases with mFOLFOX6 after a resection of the primary tumor].

We report a case of ascending colon cancer successfully treated for synchronous liver metastases with mFOLFOX6 after a resection of the primary tumor. A 79-year-old woman was diagnosed as having an ascending colon cancer with synchronous liver metastases. After right hemicolectomy, she was treated with mFOLFOX6. A partial response was observed after the fifth course and CEA decreased to a normal range (8 ng/mL). A complete response was observed after the ninth course and the treatment finished at the twelfth course. Sequentially, she was treated with UFT/LV/PSK after three courses of FOLFIRI regimen. The patient is alive without recurrence.

[Extended lymphadenectomy for gastric regional lymph node metastasis from transverse colon cancer--a case report].

We report a case of transverse colon cancer with gastric regional lymph node metastasis. A 50-year-old man was admitted to our hospital for abdominal distension and abnormal evacuation. He was diagnosed with advanced transverse colon cancer with regional lymph node metastasis by a barium enema examination and computed tomography. In operative findings, the main tumor at splenic flexure had invaded greater omentum. Therefore, left hemicolectomy with D3 lymph node dissection including gastroepiploic lymph node (classified to No. 204) was performed. Histopathological examination revealed the metastasis to gastroepiploic lymph node. Six months after initial surgery, mediastinal and hilar lymph node swelling was detected by follow-up CT scan, although mFOLFOX6 was administered as postoperative adjuvant chemotherapy. We therefore performed FOLFIRI as second-line chemotherapy. He had a stable disease during FOLFIRI. Extensive lymph node dissection of gastric region may be useful for advanced transverse cancer.

[A case of long-term disease free survival after three surgical resections for local recurrence and lung metastases from rectal cancer].

Six years ago, a 67-year-old-man underwent Mile's operation for rectal cancer. He complained of lower back pain in 1999, and was diagnosed with local recurrence from rectal cancer. The tumor invaded to the bladder, prostate, internal obturator muscle, and the piriform muscle. We performed a total pelvic resection and systemic chemotherapy with low-dose 5-fluorouracil/cisplatin. Since lung metastases were pointed in 2001, he received chemotherapy consisted of irinotecan and 5'-DFUR for 1 year, and a partial resection for lung metastasis was performed in 2002. After a partial resection for subsequent lung metastasis occurred in 2003, he has survived more than 5 years. A surgical resection is an effective treatment for a localized recurrence from colorectal cancer.