Influence of a Low-Carbohydrate High-Fat Diet on Peritoneal Inflammation, Cancer-Associated Lymphocytes, and Survival in a Murine Carcinomatous Peritonitis Model.

BACKGROUND: Low-carbohydrate high-fat diets (LCHFDs) are thought to be beneficial for metabolic support in patients with advanced cancer. However, whether LCHFDs affect the progression of carcinomatous peritonitis (CP) remains unclear. Our study examined the influence of a lard-based LCHFD on host immunity and survival in a murine CP model. METHODS: Mice were fed either a normal diet (ND) or an LCHFD ad libitum. On day 7, Panc02 cancer cells were inoculated intraperitoneally. Mice were killed on days 7, 21, and 35, and cytokine levels in the peritoneal fluid, as well as the number and phenotypes of peritoneal, splenic, and tumor-infiltrating lymphocytes were measured. Survival studies were performed with both ad libitum and isocaloric feeding in other sets of mice. RESULTS: The levels of all cytokines significantly increased in the LCHFD group compared with those in the ND group on day 21. The tumor necrosis factor α and interleukin-10 levels were higher in the LCHFD group than in the ND group on day 35. In the LCHFD group, the regulatory T-cell (Treg) number was significantly higher in the peritoneal cavity and tumor. The survival times were worse in the LCHFD group than in the ND group. CONCLUSION: The ad libitum, lard-based LCHFD feeding of CP mice increases the peritoneal cytokine levels, which may reduce splenic, anticancer lymphocytes and increase the number of Tregs in the peritoneal cavity and tumor. The detrimental effects of LCHFD are linked to dietary composition rather than overfeeding.

Influences of Short-Term Fasting and Carbohydrate Supplementation on Gut Immunity and Mucosal Morphology in Mice.

BACKGROUND: Preoperative carbohydrate (CHO) supplementation has been recommended in enhanced recovery after surgery protocols. However, the effects of CHO supplementation on gut and systemic immunity are not well understood. METHODS: Mice (n = 60) were randomized to 1 of the following 5 groups: control (ad lib feeding), 12-hour fasting without CHO administration (fasting), and 12 hours of fasting with CHO administration at 2, 4, and 8 hours before sacrifice. Then, lymphocytes were isolated from gut-associated lymphoid tissue, that is, Peyer's patches, the intraepithelial space, and the lamina propria of the small intestine. These lymphocyte numbers and phenotypes were evaluated. IgA levels in respiratory and small-intestinal washings were determined by ELISA. Morphology, proliferation, and apoptosis of the intestinal epithelium were also evaluated histologically. RESULTS: Although there were no significant differences in IgA levels among the 5 groups, fasting decreased intraepithelial and lamina propria, but not Peyer's patches lymphocyte numbers. CHO at 2 hours prevented lymphocyte loss in intraepithelial, whereas CHO at 4 hours reversed lamina propria lymphocytes numbers. Percentages of lymphocyte phenotypes were similar in each site among the 5 groups. Fasting caused villous atrophy; however, CHO at 2 hours restored villous structure along with maintenance of epithelial cell proliferation rate. CONCLUSIONS: Only 12 hours of fasting causes marked gut-associated lymphoid tissue cell loss along with gut atrophy. However, CHO at 2 hours preserves gut immunity and morphology not completely but moderately.

Cystine and Theanine Improve Survival after Gut Ischemia-Reperfusion.

BACKGROUND AND AIM: Oral administration of cystine and theanine (CT) may modulate antioxidant glutathione (GSH) metabolism, thereby improving outcomes after gut ischemia reperfusion. METHODS: Experiment 1: Institute of Cancer Research mice (n = 35) were assigned to a Vehicle (n = 11), a CT140 (n = 14), or a CT280 (n = 10) group. The CT140 and 280 groups were given CT at respective dosages of 140 and 280 mg/kg (cystine: theanine = 5: 2) once daily via gavage for 5 days. All mice underwent 75-min occlusion of the superior mesenteric artery (SMA). Survival after reperfusion was observed. Experiment 2: Mice (n = 67) were pretreated for 5 days (Vehicle: n = 24, CT280: n = 20, vehicle/sham: n = 23). The Vehicle and CT280 groups underwent 60-min SMA occlusion. Levels of GSH, the oxidized form of GSH, Glutathione-S-S-Glutathione (GSSG), and GSH-related amino acids (cysteine and glutamic acid) in the small intestine, and plasma cytokine (IL-6, IL-1ß, TNFα) levels, were evaluated before (0 h), 3, 6, or 9 h after reperfusion. RESULTS: Experiment 1: The CT280 group showed significantly better survival than the Vehicle group. Experiment 2: Gut GSSG, cysteine, and glutamic acid levels were higher in the CT280 than in the Vehicle group after reperfusion. Plasma IL-6 and TNFα levels rose more rapidly in the CT280 than in the Vehicle group. CONCLUSION: Oral administration of CT improves survival after gut I/R, possibly through the modulation of the GSH-redox cycle and cytokine responses.

Influences of Vagotomy on Gut Ischemia-Reperfusion Injury in Mice.

BACKGROUND: How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear. MATERIALS AND METHODS: Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured. RESULTS: Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group. CONCLUSIONS: Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.

Challenging Residual Contamination of Instruments for Robotic Surgery in Japan.

BACKGROUND Recently, robotic surgery has been introduced in many hospitals. The structure of robotic instruments is so complex that updating their cleaning methods is a challenge for healthcare professionals. However, there is limited information on the effectiveness of cleaning for instruments for robotic surgery. OBJECTIVE To determine the level of residual contamination of instruments for robotic surgery and to develop a method to evaluate the cleaning efficacy for complex surgical devices. METHODS Surgical instruments were collected immediately after operations and/or after in-house cleaning, and the level of residual protein was measured. Three serial measurements were performed on instruments after cleaning to determine the changes in the level of contamination and the total amount of residual protein. The study took place from September 1, 2013, through June 30, 2015, in Japan. RESULTS The amount of protein released from robotic instruments declined exponentially. The amount after in-house cleaning was 650, 550, and 530 µg/instrument in the 3 serial measurements. The overall level of residual protein in each measurement was much higher for robotic instruments than for ordinary instruments (P<.0001). CONCLUSIONS Our data demonstrated that complete removal of residual protein from surgical instruments is virtually impossible. The pattern of decline differed depending on the instrument type, which reflected the complex structure of the instruments. It might be necessary to establish a new standard for cleaning using a novel classification according to the structural complexity of instruments, especially for those for robotic surgery. Infect Control Hosp Epidemiol 2017;38:143-146.

Undifferentiated carcinoma of the gallbladder with endothelial differentiation: A case report and literature review.

Undifferentiated carcinoma of the gallbladder is a rare cancer type with a poor prognosis. The present study described a case of undifferentiated gallbladder carcinoma of the spindle- and giant-cell type, according to the 2010 World Health Organization classification. Hematoxylin and eosin staining revealed that the tumor consisted of dense interlacing bundles of spindle-shaped cells. No evidence of cartilaginous, osseous or rhabdomyosarcomatous differentiation was observed. Immunohistochemical staining revealed that spindle- and polygonal-shaped cells of the undifferentiated carcinoma were positive for cytokeratin AE1/3, vimentin and vascular endothelial growth factor. Furthermore, numerous spindle-shaped cells were positive for cluster of differentiation (CD)34 and CD31, and certain spindle-shaped cells were positive for Factor VIII. These results suggested classification of the present case as 'undifferentiated gallbladder carcinoma with endothelial differentiation'.

Time-dependent influence on assessment of contaminated environmental surfaces in operating rooms.

BACKGROUND: There is no established method to assess the contamination of environmental surfaces because the results change with time. We evaluated current methods for assessment of contamination of environmental surfaces in the operating room (OR). METHODS: Contamination of environmental surfaces in the OR was assessed using an adenosine triphosphate (ATP) test and bacterial culture. We collected 480 ATP test samples from 17 surfaces in 6 ORs to determine the influence of surface features, including frequency of touching and surface orientation on contamination, after completion of daily scheduled operations. Another 54 pairs of ATP and microbial samples were taken from 3 surfaces in each of the same OR except 1 to determine the time course of the results of ATP and microbial tests when ORs were not used. RESULTS: Multivariate analysis demonstrated that the ATP results were strongly influenced by frequency of touching and orientation of environmental surfaces. The microbial counts declined over time, whereas the ATP results remained at a high level. CONCLUSION: The ATP test result could be used as a relatively stable trace of contamination of environmental surfaces; however, it is not a surrogate indicator of the number of viable microbes which declines over time.

Occult risk of broken instruments for endoscopy-assisted surgery.

BACKGROUND: The influence of broken sophisticated surgical instruments on the safety of surgery has yet to be determined, in spite of an assumption that breakage of surgical instruments is not associated with critical incidents. The purpose of the present study was to delineate the risk from breakage of surgical instruments used in surgery assisted by endoscopy. METHODS: A retrospective analysis was conducted to determine the frequency of breakage of instruments used in 39,817 operations from 2007 to 2011. Data of breakage were collected using incident/near-incident reports and the request forms for repair of broken instruments. RESULTS: During the study period, 441 instruments were reported to be broken intraoperatively, and 7,541 were found to be broken on inspection. The incidence of breakage adjusted by the number of operations and the number of uses suggested that instruments for endoscopy-assisted surgery are broken more frequently intraoperatively than are any other type of instruments (visceral surgery: 0.039 versus 0.017, P = 0.0002, RR = 2.318; obstetrics/gynecology: 0.023 versus 0.0067, P < 0.0001, RR = 3.461; thoracic surgery: 0.019 versus 0.004, P = 0.0772, RR = 5.212). Inappropriate use and wearing out were two major possible causes of breakage of instruments. The predominant adverse events were suggested to be attributable to parts falling off broken instruments because of inappropriate use. CONCLUSIONS: Our results demonstrated that surgery assisted by endoscopy has its own occult risk, which has not been previously highlighted. Minimally invasive surgery is not necessarily safe with respect to breakage of surgical instruments. Our data provide substantial evidence for higher risk of instrument breakage in endoscopy-assisted surgery, as well as its possible detrimental effect on patient safety.

Microbial contamination of surgical instruments used for laparotomy.

BACKGROUND: The aim of this study was to determine the risk of contamination of surgical instruments according to the type of instrument and the surgical procedure. METHODS: Microbiologic examination was conducted on 140 pairs of forceps used in 24 elective laparotomies. These included 60 pairs of tissue forceps and 80 pairs of DeBakey forceps. Microbes on their surface were recovered using a membrane filter method. Adenosine triphosphate assay was also performed simultaneously in each pair of forceps. RESULTS: A total of 66 strains of microbes was recovered from 44 collected instruments (31%), with microbial counts ranging from 0 to 296 colony-forming units. Among the recovered microbes, gram-positive cocci were dominant [corrected]. The remaining microbes included 6 strains of gram-positive rods and 4 strains of gram-negative rods. The most common organism was Staphylococcus epidermidis, followed by S hominis and S warneri. Residual adenosine triphosphate was not correlated with the number of recovered microbes. CONCLUSION: Surgical instruments tend to be contaminated during operations by microbes that inhabit the skin and organs. Surgical instruments could act as fomites for the pathogens of surgical site infection even if the surgical field is not apparently contaminated, through application of appropriate practices adhering to surgical site infection guidelines.

Truncal vagotomy temporarily decreases the pro- and anti-inflammatory cytokine levels in the small intestine.

PURPOSE: The vagus nerve exerts immunomodulatory functions by inhibiting pro-inflammatory cytokine overproduction. Because vagotomy is a standard procedure during the radical operation for esophageal or gastric cancer, the postoperative clinical course might be related to vagotomy-associated changes in the cytokine milieu. We herein examined the gut cytokine kinetics after vagotomy in mice. METHODS: Thirty-eight male Institute of Cancer Research mice underwent sham or sub-diaphragmatic truncal vagotomy. The whole small intestine was harvested on postoperative day (POD) 14 (sham: vagotomy, n = 9:10) or 20 (n = 9:10). The pro- and anti-inflammatory cytokine levels in the plasma, jejunum, ileum and whole small intestine were evaluated. RESULTS: The plasma cytokine levels were similar in the vagotomy and sham groups on POD 14 and 20. However, both the pro- and anti-inflammatory cytokine levels tended to be lower on POD 14 and higher on POD 20 in the vagotomy group than in the sham group. With regard to the cytokine kinetics, the jejunal IL-12p70, TNF-α, MCP-1 and IL-10, ileal IL-12p70, TNF-α, IL-6, MCP-1 and IL-10, and whole small intestinal IL-12p70, TNF-α, IFN-γ, MCP-1 and IL-10 of the vagotomy group all significantly increased on POD 20 as compared to POD 14. CONCLUSION: Vagotomy has a major impact on the gut cytokine milieu. Vagotomy may initially inhibit both pro- and anti-inflammatory cytokine production, while both later increase.

Prevention of medical accidents caused by defective surgical instruments.

BACKGROUND: The malfunctioning of surgical instruments may lead to serious medical accidents. Limited information is available on the risk of defective instruments. The purpose of these study is to demonstrate the features of defective surgical instruments, to establish a strategy to reduce the risk of medical accidents. METHODS: We studied 19,474 consecutive operations during 2007 to 2009 at our hospital. The data on defective instruments were collected based on the orders for repair of broken instruments and reports of near-miss incidents. Adverse events caused by defective instruments were also identified from reports of near-miss incidents. RESULTS: A total of 1,775 nonfunctioning instruments were identified during the study period. Of these, 112 were found during operation. More than half of the defective instruments were tissue-grasping instruments, bone-boring/gnawing instruments, and instruments for endoscopic surgery. Wearing out and inappropriate use of instruments were 2 major causes of defects. The rest of the causes consisted of inadequate inspection and factory defects. Two near-miss incidents (incidence 10 per 100,000 operations) in endoscopic surgery were potentially critical, but the postoperative course was uneventful in each patient. The incidence of defects adjusted by the number of operations demonstrated that bone-boring/gnawing instruments and instruments for endoscopic surgery tend to be broken during surgery. Without inspection by the manufacturer, the incidence would be much higher for endoscopic instruments. CONCLUSION: Our data suggest that the appropriate use and adequate inspection of particular types of instruments are key for reducing the risk of medical accidents caused by defective surgical instruments.

Interleukin-7 treatment reverses parenteral nutrition-induced impairment of resistance to bacterial pneumonia with increased secretory immunoglobulin A levels.

BACKGROUND: Absence of enteral delivery of nutrients causes gut associated lymphoid tissue (GALT) atrophy and an imbalance between immunoglobulin A (IgA)-inhibiting Th1 and IgA-stimulating Th2 cytokine levels in the gut, leading to impaired mucosal immunity. We previously demonstrated exogenous IL-7 to reverse parenteral nutrition (PN)-induced GALT cell loss but not to normalize the gut cytokine imbalance or reduce secretory IgA levels, in uninjured mice. Herein, we examined effects of exogenous IL-7 during PN on survival and IgA levels after intra-tracheal bacterial challenge. METHODS: Sixty-five male Institute of Cancer Research (ICR) mice were randomized to chow, PN or PN+IL-7 (1 µg/kg, administered i.v. twice a day), and jugular vein catheters were inserted. The chow and PN mice received normal saline i.v. infusions instead of IL-7. After 5 d of feeding (chow or PN) and treatment, 8 × 10(7)Pseudomonas aeruginosa were instilled intra-tracheally. Survival was observed in 41 mice, while 24 were killed at 6 h after challenge and small intestinal, nasal and bronchoalveolar washings were obtained for IgA measurement. RESULTS: PN significantly reduced survival time and IgA levels in small intestine and bronchoalveolar washings compared with chow feeding. IL-7 treatment restored these parameters. Therefore, no significant differences in survival or secretory IgA levels were found between the chow and PN+IL-7 groups. CONCLUSIONS: Exogenous IL-7 reverses PN-induced impairment of resistance to respiratory tract infections associated with increased secretory IgA levels.

A case of postoperative recurrent intussusception associated with indwelling bowel tube.

Intussusception is quite uncommon in adults. We report a rare case of a 76-year-old man with small bowel intussusception induced by two indwelling bowel tubes, the first a jejunal feeding tube and the second an ileus tube. After complete reduction of the first intussusception caused by the jejunal feeding tube and adhesion, re-intussusception occurred due to the postoperative adhesion and ileus tube inserted into the bowel after the previous operation for intussusception. Finally, the part of the jejunum with re-intussusception and adhesion, including the place where the previous reduced intussusception had occurred, was resected. This case is a reminder that when there is no mucosal lesion other than an indwelling bowel tube or a hard adhesion/inflammation around intussusception, the patient should be operated on without delay for resection of the intussusception to prevent re-intussusception, even if the resected bowel is predicted to be long.

Neutrophil elastase inhibitor restores gut ischemia reperfusion-induced impairment of gut immunity with reduced plasma interleukin-6 concentrations in mice.

BACKGROUND AND PURPOSE: Gut-associated lymphoid tissue (GALT) is regarded as central mucosa-associated lymphoid tissue that influences systemic mucosal immunity. Our previous study revealed that gut ischemia and reperfusion (I/R) reduces GALT lymphocyte numbers. Because gut hypoperfusion frequently occurs in trauma, shock, and surgery patients, establishment of a therapeutic method to preserve GALT mass after gut I/R may be important for the prevention of infections. We examined the effects of sivelestat sodium hydrate, a selective inhibitor of neutrophil elastase, on GALT mass and plasma cytokine concentrations in a murine gut I/R model. METHODS: Seventy male ICR mice were randomized to the control (n = 34) or the sivelestat (n = 36) group. After intravenous cannulation of the animals, the superior mesenteric artery was occluded for 60 min. After reperfusion, physiologic saline or sivelestat 5 mg/kg hourly was infused for 24 h. Sixteen mice in the control and 22 in the sivelestat group were alive at 24 h. Twenty-six mice (n = 13 in each group) were chosen randomly for harvest of the small intestine. Lymphocytes from Peyer patches (PP), the intraepithelial space (IE), and the lamina propria (LP) were counted; and their phenotypes (αßT-cell receptor (TCR), γδTCR, CD4, CD8, B cell) were determined by flow cytometry. Cytokine concentrations (interleukin [IL]-6, IL-1ß, IL-10) in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay. RESULTS: Sivelestat treatment did not improve survival but increased PP and IE lymphocyte numbers significantly and reduced the LP CD8(+) cell percentage and plasma IL-6 concentration compared with controls. There were no significant differences between the two groups in other cell phenotypes or cytokine concentrations. CONCLUSION: Sivelestat treatment after gut I/R may be useful for maintaining gut immunity and preventing systemic inflammatory responses.

Improved survival in patients with breast rhabdoid tumors with multi-agent adjuvant chemotherapy combined with irradiation.

PURPOSE: Malignant rhabdoid tumors (MRT) have poor prognoses. Breast MRT is extremely rare; only three cases have been documented, with a mean prognosis of 7 months. Multi-agent chemotherapy with mastectomy and irradiation, as used in this case, may extend survival in breast MRT. PATIENT AND METHODS: A 68-year-old woman who underwent a standard mastectomy was diagnosed with breast MRT. Postoperatively she received six cycles of cyclophosphamide/methotrexate/5-fluorouracil followed by oral administration of doxifluridine and anastrozole, after which no metastasis was detected. About 8 months postoperative, magnetic resonance imaging revealed cervical bone metastasis, and local irradiation and nine doses of "basic chemotherapy" consisting of biweekly paclitaxel and anastrozole were administered. About 4 months later, multiple lung metastases were revealed, and four doses of "basic chemotherapy" with added pirarubicin hydrochloride were administered. Four months after that, multiple large liver metastases were discovered, and five doses of "basic chemotherapy" with added carboplatin were administered. RESULTS: The 19-month survival period of our case was almost three times that of reported breast MRT patients. CONCLUSION: Multi-agent chemotherapy combined with irradiation may be associated with the relatively long survival of the present case.