[A Case of Suspected Non-Occlusive Mesenteric Ischemia following Neoadjuvant Chemotherapy for Esophageal Cancer with an Extremely Poor Prognosis].

Non-occlusive mesenteric ischemia(NOMI)is defined as intestinal ischemia or necrosis with patency of the mesenteric arteries. Here, we report a case of suspected NOMI following neoadjuvant chemotherapy for esophageal cancer with an extremely poor prognosis. A 79-year-old man complained of weight loss and vomiting. Esophagogastroduodenoscopy revealed a tumor extending from the lower intrathoracic esophagus to the gastric cardia. He was diagnosed with esophageal cancer(small cell neuroendocrine carcinoma, T3(AD)N0M0, cStage Ⅱ)accordingly. He received cisplatin and etoposide as neoadjuvant chemotherapy. Tube feeding was initiated due to tumor stenosis. His weight increased rapidly by more than 8 kg on the second day of treatment. He did not display any signs of heart failure, and so continued chemotherapy in conjunction with diuretics. Upon completion of chemotherapy, his continued use of diuretics gradually reduced his weight. On day 7, the patient complained of nausea and experienced a decrease in blood pressure. Bicarbonate Ringer's solution was administered intravenously, but the patient lost consciousness after 3 hours. Plain computed tomography revealed massive gas collections in the portal vein, tumor wall, stomach, and ascending colon. NOMI was strongly suspected. His condition continued to deteriorate, until his demise several hours later. Here, we present the above-mentioned case and discuss the relevant literature.

Intracorporeal gastrojejunostomy in Roux-en-Y reconstruction with its efferent loop located on the patient's left side following totally laparoscopic distal gastrectomy: A case report.

The drawback of intracorporeal gastrojejunostomy using only endoscopic linear staplers in antecolic Roux-en-Y (R-Y) reconstruction with its efferent loop located on the patient's left side following totally laparoscopic distal gastrectomy (TLDG) is the occurrence of anastomotic failure, even though this reconstruction system is assumed to prevent intraoperative and postoperative twisting of the gastrojejunostomy and lifted jejunum. This case report presents two patients with gastric cancer who underwent intracorporeal gastrojejunostomy consisting of linear stapling and hand suturing in antecolic R-Y reconstruction with its efferent loop located on the patient's left side following TLDG to prevent anastomotic failure of the gastrojejunostomy. After the sacrificed jejunum was created, linear stapling of the greater curvature of the remnant stomach and the lifted jejunum without dividing the jejunum was performed. After removing the sacrificed jejunum and creating a good view of the posterior side of the stapler entry hole, the stapler entry hole was closed from the posterior side to the anterior side, using a single-layer full-thickness and serosubmucosal hand suturing technique with knotted sutures and a knotless barbed suture. No anastomotic failure of the gastrojejunostomy occurred in either patient. Intracorporeal gastrojejunostomy consisting of linear stapling and hand suturing could be an option for gastrojejunostomy in antecolic R-Y reconstruction with its efferent loop located on the patient's left side following TLDG because it can aid in the prevention of anastomotic failure.

Laparoscopic Technique and Initial Experiences of Choledocholithotomy Closure With Knotless Unidirectional Barbed Sutures After Surgery for Biliary Stone Disease.

BACKGROUND AND AIM: Between January 2012 and June 2013, we performed laparoscopic choledocholithotomy on 10 cases of common bile duct stone disease. Laparoscopic surgery for common duct stone disease is technically demanding. Particularly, laparoscopic intracorporeal suturing and knot tying for repair of choledochotomy are the most difficult skills in this operative procedures. Barbed sutures has recently been proposed to facilitate laparoscopic suturing. This is the first report demonstrating that the barbed suture could potentially improve the efficacy of the intracorporeal repair of choledochotomy following extirpation of biliary tract stones with less time needed to suture. METHODS: Consecutive 10 patients with common bile duct stones who underwent laparoscopic choledocholithotomy were enrolled in this study. Choledochotomy was closed with V-Loc sutures (15 cm V-Loc 180 sutures) for 7 patients, and a V-20 needle (26 mm, tapered) for 3 patients. RESULTS: The mean choledochotomy closure time was significantly shorter in the V-Loc group (15.2 ± 1.6 min) than in the Vicryl group (23.5 ± 1.5 min). The unidirectional barbed sutures allowed surgeons to use both their hands effectively and to focus exclusively on the placement of the subsequent stitches, without the need to maintain tension on preceding stitches to prevent slippage. And also the unidirectional barbed sutures were able to distribute tension evenly along the suture line, allowing good tissue apposition. CONCLUSION: The knotless unidirectional barbed sutures are a safe and effective tool for choledochotomy repair during surgery for common bile duct stones.

Proteomic analysis of the basic proteins in 5-fluorouracil resistance of human colon cancer cell line using the radical-free and highly reducing method of two-dimensional polyacrylamide gel electrophoresis.

5-Fluorouracil (5-FU) is widely used for the treatment of patients with advanced colon cancers and it is the mainstay of chemotherapy. However, the acquisition of resistance to 5-FU is one of the most prominent obstacles to successful chemotherapy. The purpose of this study was to identify the novel biological basis of 5-FU resistance in colon cancer cells. This study is the first comparative proteomic analysis of basic proteins between the DLD-1 human colon cancer cell line and DLD-1/5-FU its 5-FU resistant sub-line using the radical-free and highly reducing method of two-dimensional polyacrylamide gel electrophoresis, which has a superior ability in the separation of basic proteins and the quantification of post-translational modification. A densitometric analysis was performed to quantify the modulated proteins, and protein spots showing significant changes were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Six basic proteins significantly modulated between DLD-1 and DLD-1/5-FU were identified. All of them showed up-regulated expression in DLD-1/5-FU in comparison to DLD-1. The six identified spots, corresponding to five different proteins included heterogeneous nuclear ribonucleoprotein G, mitochondrial transcription factor A, histone H2B, histone H4 and ribosomal protein L3. Among the 5 basic proteins, several proteins are potentially related to 5-FU resistance by protecting the cells from DNA damage.

Laparoscopic mesorectal excision with preservation of the pelvic autonomic nerves for rectal cancer.

BACKGROUND/AIMS: Laparoscopic mesorectal excision with preservation of the autonomic pelvic nerves for rectal cancer including selected advanced lower rectal cancer is now challenging. The aims of the study were to assess the surgical results and short-term outcomes of this procedure prospectively. METHODOLOGY: Seventy-four of 281 rectal cancer patients, since the introduction of laparoscopic colorectal surgery in our hospital, have undergone laparoscopic rectal surgery. The location of the tumor distributed in upper rectum; 33, middle; 22, and lower 19. The mesorectal excision with preservation of the autonomic pelvic nerves was performed for all the patients. The laparoscopic mesorectal excision was performed under 8 to 10 cmH2O CO2 pneumoperitoneum and lymph node dissection was performed along the feeding artery depend on individuals. Ipsilateral lateral lymph node dissection was added for 5 cases of advanced lower rectal cancer. RESULTS: Open conversion occurred in 4 cases, 2 of those were due to locally advanced tumors and 2 technical difficulties in transaction of the distal rectum. There were 15 postoperative complications, 7 anastomotic leakage (10.6%), 3 transient urinary retention (4.1%), 4 wound infection (5.3%), and 1 small bowel obstruction (1.4%). No mortality was recorded in this series. Time of operation was 203 +/- 54 min in mesorectal excision cases and 270 +/- 42 min mesorectal excision with lateral lymph node dissection cases. Blood loss was 92 +/- 90g and 276 +/- 66 g respectively. The hospital length-of-stay was 11.7 days in average. CONCLUSIONS: Laparoscopic mesorectal excision with preservation of autonomic pelvic nerves for rectal cancer patients including selected advanced lower rectal cancer is favorable.

Respiratory function after laparoscopic distal gastrectomy--an index of minimally invasive surgery.

BACKGROUND: As the techniques of laparoscopic surgery have improved, various institutions have performed laparoscopic gastrectomies with regional lymph node dissection, as well as open surgery. Although alleviation of postoperative pain and prompt recovery have been reported in the literature, objective indexes of the minimal invasiveness of laparoscopic procedures are as yet very few. METHODS: We performed distal gastrectomy with regional lymph node dissection for gastric cancer patients using three kinds of procedures, namely, open gastrectomy, hand-assisted laparoscopic surgery (HALS), and totally laparoscopic gastrectomy. Ablation of the stomach, lymph node dissection, and reconstruction of the digestive tract were all carried out intracorporeally with or without HALS in the laparoscopic procedures. The ordinary respiratory function test was performed pre- and postoperatively for 50 patients operated on by each procedure, and the reduced percentages of the measured values were calculated. RESULTS: Postoperative respiratory function was consistently excellent, with minimal loss of vital capacity and forced expiratory volume per second in the totally laparoscopic group compared to HALS or open cases. CONCLUSIONS: Although it may be a complicated technique, totally laparoscopic distal gastrectomy is considered a minimally invasive procedure for gastric cancer from the viewpoint of postoperative respiratory function.

Synthesis, further biological evaluation and pharmacodynamics of newly discovered inhibitors of TNF-alpha production.

(1S,2R)-2-Acylamino-1-methyl-2-phenylethyl phosphate derivatives 2a, 2b, 3a, and 5a, which are conformationally restricted and metabolically stable analogues of (2R)-2-acylamino-2-phenylethyl phosphate derivatives 1a and 1b, are a new class of inhibitors of TNF-alpha production. More efficient alternative synthesis of a key intermediate, (1R,2S)-1-amino-1-(3-methoxyphenyl)propan-2-ol hydrochloride (9), was achieved using one-step, three-component coupling of 3-methoxyphenyl boronic acid (13), (5S)-2,2,5-trimethyl-1,3-dioxolan-4-ol (14), and amino diphenyl methane (15), [as reported in J. Am. Chem. Soc. 1998, 120, 11798]. Evaluation of the hypotensive activity of these compounds was done to assess one of their side effects. Among the compounds tested, the above-mentioned four compounds (2a, 2b, 3a, and 5a) were identified as inhibitors with both sufficient potency and an acceptable safety margin regarding their hypotensive activity. The pharmacodynamics of these compounds were also investigated. Single-dose pharmacokinetic data for compounds 2a, 2b, 3a, and 5a are displayed. These compounds were estimated to be mainly metabolized by the liver in the species tested based on their in vitro stability in tissue homogenates and plasma. A representative compound, 2a, showed good linearity of its plasma concentration after intravenous injection.

Highly potent inhibitors of TNF-alpha production. Part I: discovery of new chemical leads and their structure-activity relationships.

Discovery of new chemical leads of inhibitors for TNF-alpha production starting from the chemical modification of 1 is reported. Further biological studies of 1 to disclose the site of its action strongly suggested that 1 inhibits LPS-induced TNF-alpha expression in the liver and spleen of mice. Structure-activity relationships (SARs) are also discussed and full details including the chemistry are reported.

Highly potent inhibitors of TNF-alpha production. Part II: metabolic stabilization of a newly found chemical lead and conformational analysis of an active diastereoisomer.

Design and synthesis of metabolically stabilized inhibitors of TNF-alpha production, which could be new drug candidates, are reported. Conformational analysis of an active diastereoisomer was performed based on biological evaluations of the conformationally fixed indane derivatives 17 and 18. Structure-activity relationships (SARs) based on biological evaluations of the optically active derivatives are also discussed. Full details including chemistry are reported.

Highly potent inhibitors of TNF-alpha production. Part 1: Discovery of chemical leads.

The discovery of 2-acylamino-2-phenylethyl disodium phosphates and as structurally novel inhibitors of TNF-alpha production is reported. Structure-activity relationships (SARs) are also discussed.

Highly potent inhibitors of TNF-alpha production. Part 2: identification of drug candidates.

Metabolic stabilization of the chemical lead 1, which is a structurally novel inhibitor of TNF-alpha production, was accomplished by introducing a (1S)-methyl group into the optically active backbone. As a result, 2, 3 and 4 were identified as drug candidates and evaluated pharmacologically. The analysis of an active conformer was also carried out.