Prospective multicenter study of reduced port surgery combined with transvaginal specimen extraction for colorectal cancer resection.

PURPOSE: The relevance of transvaginal specimen extraction (TVSE) combined with reduced port surgery (RPS) remains unknown. This study investigated the feasibility of TVSE with RPS according to short-term outcomes and cosmesis. METHODS: This prospective multicenter study enrolled ten patients at three institutions. For the semi-quantification of each parameter, we administered questionnaires to assess pain (visual analogue scale), subjective/objective wound healing esthetics [photo series questionnaires (PSQ)], and quality of life (QOL). RESULTS: No operative complications occurred, except one case of urinary tract infection, which was promptly cured with antibiotics. On day 0, pain was rated at 2.3 ± 0.67 at rest and 4.9 ± 0.82 during sneezing; these ratings gradually declined over time. The PSQ showed that the patient ratings of wound esthetics after TVSE were not inferior to ratings from patients after conventional laparoscopy or single incision laparoscopic surgery, and they were significantly higher than the patient ratings of wounds after laparotomy (P < 0.05). The QOL scores showed that, in comparison to before surgery, after surgery, patients reported significant deterioration of their physical function (96.67 ± 1.49 vs. 87.33 ± 2.71), emotional function (93.33 ± 2.72 vs. 86.67 ± 2.22), fatigue (7.78 ± 3.72 vs. 26.67 ± 8.31), and pain (6.67 ± 3.69 vs. 18.33 ± 4.61). CONCLUSION: TVSE with RPS for colorectal cancer was feasible and was associated with a low degree of postoperative pain.

[A Case of Radical Resection after CapeOX Therapy for Locally Advanced Sigmoid Colon Cancer with Anemia and Abscess Formation in a Jehovah's Witness].

The patient-a Jehovah's Witness-was a woman in her 60s, with locally advanced sigmoid colon cancer. She had severe anemia, and a computed tomography scan of her abdomen showed a tumor with abscess formation and perforation that had invaded into the left urinary duct and the left ovary, without distant metastasis. It was difficult to perform curative resections without transfusion; therefore, CapeOX therapy was plannedas the neoadjuvant treatment. After 3 courses of CapeOX therapy, the patient's anemia improved, and the tumor and abscess had shrunk. Subsequently, a sigmoidectomy with D3 lymph node dissection, partial resection of the small intestine, and the left adnexectomy, as a radical surgery, were performed without blood transfusion. In cases of concomitant colon cancer with anemia that are treated with highly invasive surgery, it might be necessary to conduct systematic treatment in order to complete non-transfusion therapy.

Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors.

A series of piperazine ureas was designed, synthesized, and evaluated for their potential as novel orally available fatty acid amide hydrolase (FAAH) inhibitors that are therapeutically effective against pain. We carried out an optimization study of the lead compound 3 to improve its DMPK profile as well as in vitro potency. We identified the thiazole compound 60j with potent inhibitory activity, high brain permeability, and good bioavailability. Compound 60j showed a potent and dose-dependent anti-nociceptive effect in the acetic acid-induced writhing test in mice.

Totally laparoscopic anterior resection with transvaginal assistance and transvaginal specimen extraction: a technique for natural orifice surgery combined with reduced-port surgery.

BACKGROUND: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. However, NOSE performed using a conventional multiport technique has been reported previously. The current authors performed totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) using the reduced-port surgery (RPS) technique. The Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) and Free Access (Top Corporation, Tokyo, Japan) were attached to the transvaginal route for transvaginal assistance and smooth specimen extraction. The authors documented this simple and safe technique and its short-term results. METHODS: Data were prospectively collected for five patients who underwent totally laparoscopic anterior resection with TVSE for colorectal cancer between June 2012 and December 2012. A multiport access device (GelPOINT advanced-access platform; Applied Medical) was inserted into the navel, and a 5-mm port was inserted into the right lower quadrant to be used as a drain site. Transverse transvaginal posterior colpotomy then was performed. One ring of an Alexis ring pair was inserted into the peritoneal cavity through the vagina. The other white ring was placed outside of the vagina and then covered with a Free Access to maintain the pneumoperitoneum for insertion of a 12-mm port. Lymph node dissection and transection of the distal colon were performed with transvaginal assistance. The specimen then was extracted transvaginally. After the Alexis had been removed, the vaginal incision was closed transvaginally. End-to-end colorectal anastomosis was performed using the double-stapling technique. RESULTS: Transvaginal extraction was completed in all five cases. The median operation time was 235 min. One case was complicated by chyloperitoneum. The median hospital stay was 6 days. Only one patient required intravenous analgesics once on postoperative day 1. All the patients remained disease free. CONCLUSION: Totally laparoscopic anterior resection using TVSE with RPS appears to be feasible, safe, and oncologically acceptable for selected cases.

[A case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy].

We report a case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old man underwent right hemicolectomy for cecal cancer. After 10 months, surgical resection was performed for its local recurrence. He was then treated with FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of congestive disturbances. Through radiographic examination and laboratory data, only hyperammonemia was found; he was therefore diagnosed with hyperammonemic encephalopathy. By starting branchedamino acid solutions for its treatment, his consciousness and serum ammonia were promptly improved. Hyperammonemic encephalopathy related 5-FU is caused by increasing ammonia production and its metabolic inhibition, and is worsened by renal dysfunction, dehydration, constipation, infections, or body weight loss. On account of the potential decrease of metabolic function of liver and kidney, an aged person tends to have hyperammonnemia more than a youth. Clinicians should be aware of the adverse events associated with hyperammonemia when then administer a large amount of 5-FU to elderly patients.

[A case of locally advanced rectal cancer had a pathological complete response to XELOX Therapy].

The patient was a 62-year-old man with bowel obstruction in a locally advanced rectal cancer. Computed tomography (CT) scan of the abdomen showed tumor enlargement(11.4 × 9.0 cm)that invaded the urinary bladder, but no distant metastasis. XELOX therapy was planned in order to shrink or eliminate the tumor after a sigmoid colostomy. Four courses of XELOX therapy were perfomed. Consequently, the level of the tumor marker had been restored to a normal range. CT scan revealed marked shrinkage of the tumor (6.1 × 5.2 cm) and a sharply-defined border between the tumor and the urinary bladder. Three weeks after chemotherapy, a low anterior resection as a radical surgery, and a temporary ileostomy were performed. The post-operative course was good. The histological effect was judged to be grade 3. There were no viable cancer cells in the rectal tumor and lymph nodes. The patient is alive and has been disease-free for 10 months after the operation. XELOX therapy as pre-operative chemotherapy might be safe and effective for patients with locally advanced rectal cancer.

Totally laparoscopic sigmoid colectomy with transanal specimen extraction.

BACKGROUND: Conventional techniques for laparoscopic-assisted colectomy (LAC) require abdominal minilaparotomy for extraction of the specimen. Abdominal wound complications often increase the invasiveness of LAC. To decrease the incidence of wound complications, natural orifice specimen extraction (NOSE) has been reported. However, only a few devices that allow smooth extraction and reduced intracorporeal contamination have been reported previously. We performed totally laparoscopic sigmoid colectomy using transanal specimen extraction (TASE) and the Alexis(®) wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA). We document this simple and safe technique and its short-term results. METHODS: We prospectively collected data on 18 patients who underwent totally laparoscopic sigmoid colectomy with TASE from April 2009 to July 2010. Lymph node dissection and transection of proximal and distal colon were performed in conventional manner. The transected rectal stump was opened transversely, and a long Babcock grasper was inserted transanally through the opened rectal stump. One of a pair of Alexis rings was held and pulled out of the anus. The other ring was placed in the opened rectal stump. The specimen was then extracted transanally through the Alexis. After the Alexis had been removed, the rectal opening was reclosed with a linear stapler. End-to-end colorectal anastomosis was then performed using the double-stapling technique. RESULTS: Transanal extraction was achieved in 17 cases. We switched to conventional LAC in a case involving a bulky specimen. In 16 cases not including the combined cholecystectomy case, mean operation time was 241 min. One case was complicated by anastomotic leakage and wound infection, while another had enterocolitis. Median hospital stay was 6 days. All patients remained disease free. Mean Wexner score at 12 months after operation was 2.3. CONCLUSION: Totally laparoscopic sigmoid colectomy using TASE and the Alexis appears to be feasible, safe, and oncologically acceptable for selected cases.

The Temperature Coefficients of Frequency of Surface Acoustic Wave Devices With SiOxNy Passivation Films on LiTaO3 Substrates.

This work assessed the possible correlation between the refractive index of a SiOxNy passivation film on a surface acoustic wave (SAW) device and the temperature coefficient of frequency (TCF) of the device itself. The data demonstrate that the refractive index does correlate with the TCF as well as the frequency of the one-port resonator. SiOxNy passivation films having an optimal refractive index can potentially suppress the frequency shifts caused by the deposition of such layers, and can change the TCF from that for a Si3N4 film to that for SiO2. The results also show that the coupling coefficient of the one-port resonator increases when using a SiOxNy film with a lower refractive index, which changes the TCF such that this value approaches that for a SiO2 film. Finite-element method spectral domain analyses established that the frequency responses of the one-port resonators were affected by the velocity and temperature coefficient of velocity of the dielectric films deposited on the interdigital transducer electrodes. Thus, adjusting the refractive index of the SiOxNy film can be used to control the properties of an SAW device, including the TCF.

International consensus on natural orifice specimen extraction surgery (NOSES) for colorectal cancer.

In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.

Right-sided Bochdalek hernia in an elderly adult: a case report with a review of surgical management.

BACKGROUND: Bochdalek hernias are one of the most common types of diaphragmatic hernia, with most cases diagnosed during the neonatal period. In contrast, diagnosis of a Bochdalek hernia in an adult is rare and is typically observed on the left side of the diaphragm. Even more rare is the diagnosis of a right-sided Bochdalek hernia in an adult, where there is concurrent visceral malformation in most cases. CASE PRESENTATION: We describe a case of an 89-year-old female who presented with abdominal pain. An abdominal computed tomography (CT) scan showed decreased intravenous contrast uptake and thickening of the wall of herniated small intestine through the right side of the diaphragm, which led to the diagnosis of a strangulated diaphragmatic hernia. The patient underwent emergent laparotomy and required a partial resection of the necrotic ileum and a hernia repair with direct closure. Interestingly, in this case, organ malformation was not observed. The patient was discharged approximately 2 weeks after surgery without complication. CONCLUSIONS: Adult right-sided Bochdalek hernia with strangulation in the absence of hepatic atrophy is a rare entity. Considering the severity of this condition, accurate diagnosis and proper treatment are needed. A tailored operative approach is required on an individual case basis.

Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta.

Metastin is encoded by a putative human metastasis suppressor gene KiSS-1, and is the cognate ligand of a G-protein-coupled receptor designated OT7T175. To study the physiological function(s) of metastin, we cloned rat and mouse KiSS-1 cDNAs both encoding 130-amino acid KiSS-1 proteins. Sequence analysis suggested that processing of the rat and mouse KiSS-1 proteins produces 52-amino-acid peptides, each with an amidated carboxyl terminal and with a single possible disulfide bond, corresponding to rat and mouse metastins. The carboxyl-terminal sequence of metastin, known to be essential for functional receptor interaction, was found to be highly conserved among humans and rodents. Real-time PCR analysis indicated that rat KiSS-1 mRNA showed the highest expression level in the cecum and colon. Since KiSS-1 mRNA and metastin are known to be abundant in human placenta, we further studied the localization of KiSS-1 and OT7T175 mRNAs in rat placenta by in situ hybridization. KiSS-1 and OT7T175 mRNAs were specifically detected in trophoblast giant cells at embryonic day 12.5, and the transcripts in the cells gradually decreased during placental maturation. These results suggest that metastin/OT7T175 signaling may participate in implantation of the mammalian embryo, placenta formation, and maintenance of pregnancy.

[A case of rhabdomyolysis associated with Salmonella encephalopathy].

We report a case of severe rhabdomyolysis associated with Salmonella encephalopathy. A 3-year-old girl was admitted to our hospital because of status convulsives and unconsciousness. She was diagnosed as having Salmonella encephalopathy with rhabdmyolysis, and was treated by mild hypothermia and mechanical ventilation. Five days later she developed anuria with increased serum levels of myoglobin, CK and creatinine. And the diagnosis of acute renal failure was made. Peritoneal dialysis was begun from 6 days after admission. Hyperinfusion, the usual therapy of rhabdomyolysis, was not performed. She survived showing gradual improvement of renal function and consciousness. In a case of rhabdomyolysis complicating a neurologic disorder, a well-known poor prognostic factor, priority should be given to brain protection rather than to symptomatic treatment of rhabdomyolysis.

[A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy].

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.

Imatinib therapy for a patient with metastasis of colonic gastrointestinal stromal tumor: report of a case.

Gastrointestinal stromal tumors (GISTs) developing in the colon are rare, accounting for <5 % of all GISTs. There are few data on the clinical efficacy of tyrosine kinase inhibitors in colonic GISTs. We report here on an 80-year-old male patient with advanced GIST of the transverse colon. The patient underwent palliative resection of the primary tumor because the disease was associated with multiple liver metastases and peritoneal dissemination. Immunohistochemical analysis of the surgical specimens showed KIT and CD34 expression. Sequence analysis revealed that the tumor harbored deletion mutation at codons 557-558 in exon 11 of the c-kit gene. A diagnosis of colonic GIST was made. The patient postoperatively underwent imatinib therapy for the remaining metastatic tumors. Imatinib therapy induced a cyst-like appearance of the liver metastases and stabilized the disease. In the present case, c-kit gene analysis was found to be clinically helpful for validating the diagnosis and therapeutic decision making for this rare disease.

Diagnosis of ischemic small bowel disease by measurement of serum intestinal fatty acid-binding protein in patients with acute abdomen: a multicenter, observer-blinded validation study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is a low-molecular-mass (15 kDa) cytosolic protein found exclusively in the epithelial cells of the small bowel mucosa. We aimed to evaluate the clinical usefulness of serum I-FABP measurement for the diagnosis of ischemic small bowel disease. METHODS: Patients with a clinical diagnosis of acute abdomen were recruited for this multicenter trial at one university hospital and nine city hospitals over a 13-month period. Serum I-FABP levels were measured in 361 eligible patients by an enzyme-linked immunosorbent assay using a specific monoclonal antibody. RESULTS: Of the 361 patients, 242 underwent surgery, and small bowel ischemia was diagnosed in 52 patients. The mean serum I-FABP level in the patients with small bowel ischemia was 40.7 ± 117.9 ng/ml, which was significantly higher than that in patients with non-ischemic small bowel disease (5.8 ± 15.6 ng/ml) and those with non-small bowel disease (1.8 ± 1.7 ng/ml). The serum I-FABP cutoff level for the diagnosis of small bowel ischemia was 3.1 ng/ml. Serum I-FABP was more efficient than conventional biochemical markers, in terms of sensitivity and positive and negative predictive values, in the diagnosis of small bowel ischemia. However, its specificity was slightly lower than that of creatinine phosphokinase or lactate dehydrogenase. The positive and negative likelihood ratios of serum I-FABP were 3.01 and 0.29, respectively. CONCLUSION: Serum I-FABP measurement is a non-invasive method that is potentially useful for the efficient identification of patients with acute abdomen who are at risk of small bowel ischemia.

Phase I/II trial of combination therapy with S-1 and weekly paclitaxel in patients with unresectable or recurrent gastric cancer.

PURPOSE: We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting. PATIENTS AND METHODS: The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m(2)) was given orally on days 1-21 every 35-day cycle (rest on days 22-35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m(2), stepping up to 70 mg/m(2) in 10-mg/m(2) increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed. RESULTS: The MTD of paclitaxel was estimated to be 60 mg/m(2), because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). In the phase II portion, 22 patients were evaluated with 50 mg/m(2) paclitaxel and 80 mg/m(2) S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2-75.6%). The median survival time was 283 days (95% CI, 218-508 days). The median number of treatment courses was 4 (range 1-10), indicating that this regimen could be given repeatedly. CONCLUSIONS: This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.

Segmental adenomyomatosis of the gallbladder predisposes to cholecystolithiasis.

BACKGROUND/PURPOSE: The aim of the present study was to clarify the association between adenomyomatosis of the gallbladder and cholecystolithiasis. METHODS: A cholecystectomy was performed for cholelithiasis or various other conditions in 1099 patients, of whom 608 had cholecystolithiasis. Adenomyomatosis of the gallbladder was classified as one of three variants: segmental, fundal, and diffuse. Segmental adenomyomatosis has an annular stricture dividing the gallbladder lumen into the "neck compartment" and the "fundal compartment". Bile lipid analysis was performed in 8 patients with segmental adenomyomatosis. RESULTS: Adenomyomatosis of the gallbladder was observed in 156 patients (14.2%), of whom 99 had segmental adenomyomatosis, 54 had fundal adenomyomatosis, and 3 had diffuse adenomyomatosis. The prevalence of cholecystolithiasis was higher in patients with segmental adenomyomatosis (88.9%) than in those without adenomyomatosis (52.3%; P < 0.001). Gallstones were detected earlier in patients with segmental adenomyomatosis than in those without ( P < 0.001) and were located predominantly in the fundal compartment. Bile in the fundal compartment had lower concentrations of total bile acids ( P = 0.012), with an increased cholesterol saturation index ( P = 0.012), compared to bile in the neck compartment. CONCLUSIONS: Segmental adenomyomatosis is a condition predisposing to cholecystolithiasis, probably due to the lithogenic environment in the fundal compartment. Fundal or diffuse adenomyomatosis appears to be unrelated to cholecystolithiasis.