Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements.

An association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements.

Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients.

BACKGROUND: The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. METHODS: This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. RESULTS: All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6-46) and 7 (range, 2-18), respectively (P < 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m(2) (range, 408.7-3385.3 mg/m(2)) in the OXY group and 483.0 mg/m(2) (range 76.2-1414.1 mg/m(2)) in the non-OXY group (P < 0.05). CONCLUSIONS: Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.

Association between genetic polymorphisms of the ß1-adrenergic receptor and sensitivity to pain and fentanyl in patients undergoing painful cosmetic surgery.

Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, can hamper effective pain treatment. The adrenergic system is reportedly involved in the mechanisms of pain and analgesia. Here, we focused on one of the adrenergic receptor genes, ADRB1, and analyzed the influence of single-nucleotide polymorphisms (SNPs) in the ADRB1 gene on individual differences in pain and analgesic sensitivity. We examined associations between pain and fentanyl sensitivity and the two SNPs, A145G and G1165C, in the human ADRB1 gene in 216 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. The patients who carried the A-allele of the A145G SNP were more sensitive to cold pressor- induced pain than those who did not carry this allele, especially in male patients. The analgesic effect was significantly less in females who carried the G-allele of the G1165C SNP than the females who did not carry the G-allele. The haplotype analysis revealed a significant decrease in 24-h postoperative fentanyl use in female 145A/1165C haplotype carriers. These results suggest that SNPs in the ADRB1 gene are associated with individual differences in pain and analgesic sensitivity, and analyzing these SNPs may promote personalized pain treatment in the future.

Comparison of laparoscopy-assisted and total laparoscopic Billroth-I gastrectomy for gastric cancer: a report of short-term outcomes.

BACKGROUND: The safety and efficacy of laparoscopic gastrectomy in the treatment of early gastric cancer have been demonstrated in many clinical studies. Most surgeons prefer laparoscopy-assisted gastrectomy with extracorporeal anastomosis rather than total laparoscopic procedures because of the technical difficulties of intracorporeal anastomosis. This study assessed the efficacy of total laparoscopic Billroth-I (B-I) gastrectomy. METHODS: We conducted a retrospective analysis of a single surgeon's experience. We reviewed patients with gastric cancer who underwent laparoscopic B-I gastrectomy (n=83) and classified them into laparoscopy-assisted distal gastrectomy (LADG; n=41) and total laparoscopic distal gastrectomy (TLDG; n=42) groups. Short-term surgical variables and outcomes were compared between the groups. RESULTS: There was no difference in gender, mean age, body mass index, or tumor characteristics between the groups. Estimated blood loss was significantly less in TLDG (21.2±36.8 g) than in LADG (62.5±81.6 g). Anastomotic leakage was not recorded in either group, and there was no difference in the incidence of other postoperative complications. Postoperative hospital stay was shorter for TLDG (10.6±2.6 days) than for LADG (12.0±3.5 days). Serum C-reactive protein level on day 7 after surgery was significantly lower in TLDG (2.58±2.57 mg/ml) than LADG (4.85±6.17 mg/ml); however, the level on day 1 or 4 was not significantly different. There was no difference in nutritional status or clinical symptoms during the 3 months after surgery. CONCLUSIONS: TLDG can be performed safely after appropriate experience with LADG. Our results imply that TLDG may lead to faster recovery, better cosmesis, and improved quality of life in the short-term compared with LADG. Because of the limitations of a retrospective analysis on the study and a patient selection bias, a prospective randomized study should be conducted to reach definitive conclusions.

Effectiveness of a team participation training course for laparoscopy-assisted gastrectomy.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for stomach cancer is increasingly performed in Japan and Korea. However, the procedure still is considered to be complicated, and the optimal education system for trainees has not been established to date. METHODS: The authors organized a 1-day professional training course termed the LADG Basic Lab Course for LADG beginners. The participants were required to apply as a team of two surgeons and two operating nurses. The training course consisted of lectures and a live porcine lab emphasizing use of the ultrasonically activated device and the flexible laparoscope as well as team cooperation. The quality and effectiveness of the course were evaluated 6-10 months (mean, 8.2 +/- 2.2 months) after the course using a survey form sent to a representative surgeon of each institution. RESULTS: From May 2007 to July 2008, a total of 80 colleagues (47 surgeons and 33 nurses) from 20 different centers in Japan participated in the training course. These surgeons represented 12.4 +/- 6.2 postgraduate years of education and had performed 2.7 +/- 4.9 LADGs before taking the course. In the follow-up evaluation, 12 institutions (60%) completed the survey forms. The mean operation time was reduced for eight respondents (66.7%). The number of LADGs performed per month increased in 50% of the respondents' institutions. The degree of lymph node dissection in LADG was extended for 66.7% of the respondents. The respondents answered that 100% of the first operators showed improvement in skills, as did 59.5% of the scope operators and 59.5% of the nurses. CONCLUSIONS: The training course was an effective means of introducing LADG to each institution. Training courses emphasizing explanations of key devices and teamwork may be effective for the introduction of advanced laparoscopic surgeries.

Intracorporeal circular-stapled esophagojejunostomy using hand-sewn purse-string suture after laparoscopic total gastrectomy.

BACKGROUND: Laparoscopic total gastrectomy (LTG) has not gained widespread acceptance because of technical difficulties, especially esophagojejunal anastomosis. Various modified procedures for reconstruction have been reported, but an optimal method has not been established. The authors report a circular-stapled anastomosis using hand-sewn purse-string sutures, which is a simple and classic method. However, no previous study has assessed its reliability. METHODS: From September 2008 to May 2009, 10 consecutive patients (9 men and 1 woman) with gastric cancer underwent LTG at the authors' institution. These patients had a median age of 63.7 years (range, 45-80 years) and a body mass index of 22.4 kg/m(2) (range, 18-26 kg/m(2)). After transection of the abdominal esophagus, a hand-sewn purse-string suture along the cut end of the esophagus was performed using 3-0 monofilament thread. An anvil head then was inserted into the esophagus, and the thread was tied. A monofilament pretied loop suture was added to reinforce the ligation. After the creation of an Roux-en-Y jejunal limb, laparoscopic esophagojejunal anastomosis was performed using a circular stapler inserted via a surgical glove attached to a wound retractor at the incision point at the umbilicus. The jejunal stump was closed with an endoscopic linear stapler. RESULTS: Laparoscopic esophagojejunostomy was performed successfully for all the patients. No postoperative complications related to anastomosis occurred. In one patient, an intraabdominal abscess developed postoperatively and was treated conservatively. The mean operation time was 257 min, and the estimated blood loss was 69 ml. CONCLUSIONS: With the described method, esophagojejunostomy can be performed as in conventional open surgery. Hand-sewn purse-string suturing is demanding technically, but it can be performed safely by experienced laparoscopic surgeons. This technique is feasible and can lower the cost of the laparoscopic procedure. It may be considered in countries with limited access to other special devices.

[Ten cases of advanced gastro-intestinal cancer that required preoperative dosage of PSK].

We examined ten convalescent cases of local progression digestive organ cancer, which required a radical operation after a 2-week administration of preoperative dosage of PSK. Because adjuvant chemotherapy was performed for all of the cases, 3 out of 5 advanced gastric cancer patients and 4 out of 5 advanced colorectal cancer patients had more than 5-year survival. We might be effective in controlling a host immune compromise for the lap art period, which was our aim, how long preoperative PSK dosage has contributed for the extension of survival duration. We also examined the influence of the dosage in this study in preoperational of PSK, which gave a host immune compromise by the operational aggression so far, and we reported it as well.

Morphological and Biological Characteristics of Staphylococcus aureus Biofilm Formed in the Presence of Plasma.

Characteristics of Staphylococcus aureus infections include biofilm formation, leading to the spread of bacteria to the bloodstream causing sepsis and metastatic infections. In particular, in methicillin-resistant S. aureus (MRSA) infections, biofilm formation critically hampers treatment and causes poor prognosis. We explored the biofilm formation of MRSA in the presence or absence of plasma and compared morphological characteristics, accumulation of antibiotics, and resistance to bactericidal activity, using continuous optimizing confocal reflection microscopy. Addition of plasma significantly increased biofilm formation, which is characterized by an uneven surface and aggregation of bacteria (hereafter plasma biofilm). The flow-cell system, which enabled a continuous supply of plasma, accelerated biofilm formation in both the tested strains of MRSA (BAA1556 and N315). Accumulation of green fluorescence-labeled vancomycin was observed within 5 minutes in the plasma-free biofilm, but not in the plasma biofilm. Delay of accumulation was also observed for daptomycin in plasma biofilm. Plasma biofilm bacteria were more resistant to anti-MRSA antibiotics than plasma-free biofilm bacteria. These data demonstrate that the plasma biofilm of S. aureus is substantially different from the plasma-free biofilm. Plasma biofilm, especially in the flow-cell system, could be a clinically relevant model to analyze MRSA infections and treatment.

[Regulation of perioperative immunological changes following laparotomy--effects of PSK on surgical stress].

Immune responses have been reported to decline following surgical stress, leading to an increased susceptibility to infection or to the growth of tumors. We report that preoperative treatment with PSK can inhibit the decline of immunocompetence during the perioperative period. BALB/c mice were laparotomized, and then the abdomens were closed. The concentrations of IL-6 and of IFN-gamma and IL-4 were measured. PSK treatment controlled the stress induced elevation. It was lower in the group with surgical stress than in the cultures derived from the non-treated group. The IFN-gamma concentration in the group with PSK was significantly higher than the level in the group with surgical stress alone. The IL-4 concentration was significantly lower in the surgical stress group than the control group. However, the concentration tended to be higher in the surgical stress + PSK treatment group than the group with surgical stress alone. The IFN-gamma/IL-4 ratio in the group with surgical stress was lower than the ratio in the non-treated group. The ratio in the group with PSK treatment was significantly higher than the ratio in the group with surgical stress alone. These results suggest that PSK restores the abnormality of the biological responses induced by surgical stress and corrects the reduced Th1/Th2 cytokine balance to a normal level.

Enhancement of antitumor effect of tegafur/uracil (UFT) plus leucovorin by combined treatment with protein-bound polysaccharide, PSK, in mouse models.

We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV) and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly. UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

Proximal Gastrectomy with Double Tract Reconstruction Is an Alternative Revision Surgery for Intractable Complications After Sleeve Gastrectomy.

Gastric leakage and stricture are challenging complications of sleeve gastrectomy (SG). Failure of endoscopic intervention necessitates revision surgery. We describe two cases in which proximal gastrectomy with double tract reconstruction (PG with DTR) was performed in patients with chronic gastric fistula and twisted gastric tube after SG. Following resection of the affected part of the proximal stomach, reconstruction was achieved with three anastomoses [esophagojejunostomy (EJ), gastrojejunostomy (GJ), and jejunojejunostomy]. DTR provides two exit routes, the remnant stomach and the distal jejunum. The GJ was created 15 cm below the EJ with a stoma 10 mm in diameter, which can pass a standard endoscope. Both cases were a success without any short-term complications. PG with DTR could be an alternative option for refractory complications of SG.

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies.

BACKGROUND: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. RESULTS: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. CONCLUSIONS: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

Regulation of perioperative immunological changes following laparotomy: effects of biological response modifier (BRM) on surgical stress.

Immune responses have been reported to decline following surgical stress, leading to an increased susceptibility to infection or to the growth of tumors. In this study, we report that pre-operative treatment with the biological response modifier (BRM) polysaccharide Kureha (PSK) can inhibit the decline of immunocompetence during the perioperative period. BALB/c mice were laparotomized, the intestinal tracts were exposed to room air for 1.5 h, and then the abdomens were closed. Six hours after the operation, the spleen and serum were collected. The concentrations of IL-6 in the serum and of IFNgamma and IL-4 in the supernatant of splenocyte cultures were measured. In the surgical stress group that received surgical stress and the PSK treatment, the serum IL-6 concentration was significantly elevated in the group with surgical stress. PSK treatment controlled the stress-induced elevation. IFNgamma concentrations were measured in the supernatant of Concanavalin A (Con A) stimulated splenocyte cultures. It was lower in the group with surgical stress than in the cultures derived from the non-treated group. The IFNgamma concentration in the group with surgical stress plus PSK treatment was significantly higher than the level in the group with surgical stress alone. The IL-4 concentration was significantly lower in the surgical stress group than in the control group, however, the concentration tended to be higher in the surgical stress plus PSK treatment group than in the group with surgical stress alone. The IFNgamma/IL-4 ratio in the group with surgical stress was lower than the ratio in the non-treated group. The ratio in the group with surgical stress plus PSK treatment was significantly higher than the ratio in the group with surgical stress alone. These results suggest that PSK restores the abnormality of the biological responses induced by surgical stress and corrects the reduced Th1/Th2 cytokine balance to a normal level.

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma.

One of the major obstacles in the treatment of hepatocellular carcinoma (HCC) is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the expression of ATP7B has not previously been addressed in human liver and HCC. Our purpose was to investigate ATP7B expression in human liver and hepatocellular carcinoma and its clinical significance. We retrospectively examined the expression of ATP7B in primary hepatocellular carcinoma. Immunohistochemical analysis of ATP7B was performed using a monoclonal antibody against ATP7B in 19 surgically removed hepatocellular carcinomas. A variable degree of cytoplasmic staining of tumor cells was observed in 21.1% (4/19) of the analyzed carcinomas. ATP7B expression was not observed in normal hepatic cells. Strong expression of ATP7B was observed in all the analyzed bile ducts. These findings suggest that overexpression of ATP7B in hepatocellular carcinoma might be associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Further, ATP7B is expressed in bile duct epithelial cells, where it may mediate copper secretion into bile fluid.

Percutaneous transesophageal gastro-tubing for management of gastric leakage after sleeve gastrectomy.

Gastric leakage is a challenging complication of sleeve gastrectomy. Multimodal approaches, including drainage, clipping, and stenting of the leak, are occasionally insufficient. We report successful management of refractory gastric leakage using percutaneous transesophageal gastro-tubing (PTEG). Drainage and stenting proved inadequate for treating sleeve leakage near the esophagogastric junction in two patients. PTEG was finally performed, and enteral feeding was started on the following day. The patients were discharged within 1 week. The PTEG-tube was removed after confirming oral food intake. Both patients continue to do well without recurrence. PTEG was developed for patients who are unsuitable for percutaneous endoscopic gastrostomy. PTEG provides decompression and permits enteral feeding in patients refractory to other endoscopic treatments. PTEG is an option for managing intractable sleeve leakage without surgery.

Tumor-like growth of giant inflammatory polyposis in a patient with ulcerative colitis.

We report a unique case of giant obstructing inflammatory polyposis associated with ulcerative colitis (UC). A 25-year-old Japanese man with an UC history of 2 years and 6 months was referred to our institution because of diarrhea and melena. His computed tomography scan showed marked dilation of the transverse and descending colon; therefore, we performed total colectomy. Macroscopic evaluation of the excised specimen indicated constricting lesions with giant polyposis in the transverse and descending colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregular ulcers. Histologic evaluation of the excised specimen indicated transmural inflammation with a thickened proper muscular layer overlaid with inflammatory polyposis. Based on these data, a diagnosis of giant inflammatory polyposis should be considered in patients who have had UC. Although giant inflammatory polyposis is considered benign, surgical treatment may be indicated to avoid serious complications.

Laparoscopic transhiatal resection for Siewert type II adenocarcinoma of the esophagogastric junction: operative technique and initial results.

Laparoscopic distal gastrectomy has gained wide acceptance, and laparoscopic total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG) are now also performed for gastric cancer. We extended these techniques to treat Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Ten patients with clinical T1 AEG type II underwent laparoscopic transhiatal (LTH) resection combined with LTG reconstructed by Roux-en-Y (LTH+LTG: n=2) or LPG reconstructed by jejunal interposition (LTH+LPG: n=8). Intracorporeal esophagojejunostomy was performed using a circular stapler, of which the anvil head was introduced transabdominally or transorally. The median operation time was 243 minutes, and blood loss was 25.5 g. There were no intraoperative complications or conversion to open surgery. No anastomotic leak was observed, but 1 diaphragmatic herniation to the left thoracic cavity occurred postoperatively. The median length of the proximal margin was 14.5 mm. This operation is technically feasible and can be safely performed after adequate experience of LTG or LPG, though esophagojejunostomy in the mediastinum is technically demanding.

Sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery: A case report.

We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis.

A case of recurrent invasive lobular carcinoma of the breast found as metastasis to the duodenum.

A 57-year-old woman underwent modified radical mastectomy for cancer of the left breast (stage IIB) in February 2004. Invasive lobular carcinoma was diagnosed on histopathological examination. The patient received postoperative chemotherapy and endocrine therapy on an outpatient basis and was observed. In August 2005, anorexia developed. Blood chemical tests showed elevated levels of liver enzymes and bilirubin. Computed tomography (CT) of the abdomen revealed an enlarged duodenum and dilated intrahepatic biliary and pancreatic ducts. Upper gastrointestinal endoscopy showed edema of the duodenum. A biopsy yielded a diagnosis of poorly differentiated adenocarcinoma. Duodenal carcinoma was suspected, and a pancreatoduodenectomy was performed. Duodenal metastasis from invasive lobular carcinoma was diagnosed on postoperative histopathological examination. After surgery, the patient recovered uneventfully and was discharged from the hospital. In March 2006, bilateral hydronephrosis apparently caused by peritoneal metastasis developed, and she subsequently died. Invasive lobular carcinoma is characterized by the development of gastrointestinal metastases and is rarely detected before autopsy. We describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the duodenal wall was definitively diagnosed on laparotomy.