The effects of resistance exercise and leucine-enriched essential amino acid supplementation on muscle mass and physical function in post-gastrectomy patients: a pilot randomized controlled trial.

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements.

Early Ambulation Shortened the Length of Hospital Stay in ICU Patients after Abdominal Surgery.

The optimal time to ambulation remains unclear for intensive care unit (ICU) patients following abdominal surgery. While previous studies have explored various mobilization techniques, a direct comparison between ambulation and other early mobilization methods is lacking. Additionally, the impact of time to ambulation on complications and disuse syndrome prevention requires further investigation. This study aimed to identify the optimal time to ambulation for ICU patients after abdominal surgery and considered its potential influence on complications and disuse syndrome. We examined the relationship between time to ambulation and hospital length of stay (LOS). Patients were categorized into the nondelayed (discharge within the protocol time) and delayed (discharge later than expected) groups. Data regarding preoperative functioning, postoperative complications, and time to discharge were retrospectively collected and analyzed. Of the 274 postsurgical patients managed in the ICU at our hospital between 2018 and 2020, 188 were included. Time to ambulation was a significant prognostic factor for both groups, even after adjusting for operative time and complications. The area under the curve was 0.72, and the cutoff value for time to ambulation was 22 h (sensitivity, 68%; specificity, 77%). A correlation between time to ambulation and complications was observed, with both impacting the hospital LOS (model 1: p < 0.01, r = 0.22; model 2: p < 0.01, r = 0.29). Specific cutoff values for time to ambulation will contribute to better surgical protocols.

Clinical Utility and Characteristics of the LARS Score Compared to the CCIS.

PURPOSE: The low anterior resection syndrome (LARS) score (LS) has been widely validated and has become an international tool for evaluating postoperative bowel dysfunction. However, many physicians still use the conventional incontinence scores in LARS treatment. Moreover, interpretation of LS and its relationship with conventional incontinence scores are not yet well understood. Here we compared the LS with the Cleveland Clinic Incontinence Score (CCIS) to clarify the clinical utility and characteristics of the LARS score. METHODS: We performed a multicentre observational study, recruiting 246 rectal cancer patients following sphincter-preserving surgery. Patients completed the LS, CCIS, and SF36 questionnaires. RESULTS: The response rate was 76.4%, and a total of 180 patients were analysed. The LS was strongly correlated with the CCIS (P < 0.001, rs = 0.727). However, among 116 patients determined to not have incontinence (CCIS 0-5), 51 (44%) were diagnosed with LARS (29 with minor LARS and 22 with major LARS). Among 68 patients without LARS, only 3 were diagnosed as having incontinence (CCIS > 6). In comparison with background factors, aging and elapsed time were associated with only LS. High LS and CCIS both showed significant quality-of-life impairment as assessed by the SF-36. CONCLUSION: This is the first study to determine the difference in the numeric values between the CCIS and LS. The LS can be a convenient tool for LARS screening, identifying a wide range of patients with LARS, including those with incontinence evaluated by CCIS. Assessment using the CCIS may often underestimate LARS.

Factors Affecting the Length of Hospital Days After Laparoscopic Gastrectomy for Elderly Patients with Gastric Cancer.

PURPOSE: To clarify the factors affecting the length of hospitalization after laparoscopic gastrectomy based on the physical function, body composition, and postoperative course of the patients. METHODS: Of the patients with gastric cancer who underwent laparoscopic resection at the Ageo Central General Hospital, Japan, during 2018-2019, 51 underwent physical therapy. Data regarding the objective variables, such as length of postoperative hospital stay, and baseline attributes, such as age, body weight, body mass index (BMI), and corrected limb muscle mass, postoperative course (operation time, the estimated blood loss, the day before walking independently), preoperative physical function (grip strength, 6-min walking distance), and preoperative respiratory function (vital capacity [VC]%, one-second rate) were collected retrospectively from the medical records and analyzed using multiple regression plots. RESULTS: The most suitable hospital day model after surgery is one that incorporates the total postoperative course, respiratory function, physical function (R2 = 0.45, p < 0001), and operation time (ß = 0.12, p < 0.06). The information of the day before independent walking (ß = 0.68, p < 0.001) and % VC (ß = -0.19, p < 0.04) was extracted as factors. CONCLUSION: We concluded that the operation time, walking independence days, and % VC influence the postoperative length of hospital days.

Antinociceptive effect of selective G protein-gated inwardly rectifying K+ channel agonist ML297 in the rat spinal cord.

The G protein-gated inwardly rectifying K+ (GIRK) channels play important signaling roles in the central and peripheral nervous systems. However, the role of GIRK channel activation in pain signaling remains unknown mainly due to the lack of potent and selective GIRK channel activators until recently. The present study was designed to determine the effects and mechanisms of ML297, a selective GIRK1/2 activator, on nociception in the spinal cord by using behavioral studies and whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurons. Rats were prepared for chronic lumber catheterization and intrathecal administration of ML297. The nociceptive flexion reflex was tested using an analgesy-meter, and the influence on motor performance was assessed using an accelerating rotarod. We also investigated pre- and post-synaptic actions of ML297 in spinal cord preparations by whole-cell patch-clamp recordings. Intrathecal administration of ML297 increased the mechanical nociceptive threshold without impairing motor function. In voltage-clamp mode of patch-clamp recordings, bath application of ML297 induced outward currents in a dose-dependent manner. The ML297-induced currents demonstrated specific equilibrium potential like other families of potassium channels. At high concentration, ML297 depressed miniature excitatory postsynaptic currents (mEPSCs) but not their amplitude. The ML297-induced outward currents and suppression of mEPSCs were not inhibited by naloxone, a µ-opioid receptor antagonist. These results demonstrated that intrathecal ML297 showed the antinociceptive effect, which was mediated through direct activation of pre- and post-synaptic GIRK channels. Selective GIRK channel activation is a promising strategy for the development of new agents against chronic pain and opioid tolerance.

Lung cancer risk stratification using methylation profile in the oral epithelium.

BACKGROUND: Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. METHODS: A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. RESULTS: The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). CONCLUSIONS: The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.

A phase II study of NK012, a polymeric micelle formulation of SN-38, in unresectable, metastatic or recurrent colorectal cancer patients.

PURPOSE: NK012 is a polymeric micelle formulation of SN-38, the active metabolite of irinotecan. We evaluated the efficacy and safety of NK012 in Japanese patients with unresectable metastatic colorectal cancer. METHODS: We conducted a multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients with UGT1A1 genotype -/-, *6/-, or *28/-; group B: 5 patients with UGT1A1 genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR). Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were administered intravenously over 30 min, and these doses were subsequently administered every 3 weeks. Group A was evaluated as the primary efficacy population, while group B was evaluated for reference. RESULTS: In group A, the RR was 3.8%, and the median progression-free survival and overall survival were 3.30 months and 15.03 months, respectively. In both groups, the most common grade ≥ 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade ≥ 3 diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10 patients (17%); all improved or recovered. In group B, no serious ADRs were observed. No treatment-related deaths were reported in either group. CONCLUSIONS: NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that was reported in the phase III EPIC trial (4.2%), and the incidence of grade ≥ 3 diarrhea was low. Based on the incidence and severity of febrile neutropenia and grade ≥ 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for colorectal cancer patients who have previously been treated with an oxaliplatin-based chemotherapy regimen.

A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC 0902).

BACKGROUND: This study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients. METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age ≥ 20 years; Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m(2) oxaliplatin on day 1 plus 1,000 mg/m(2) capecitabine b.i.d. on days 1-14) every 3 weeks. The primary endpoint was confirmed objective response rate. RESULTS: The study included 47 patients (male/female 30/17; median age 69 years; age range 38-81 years with 10 patients ≥ 75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0-67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8-12.3) and 34.6 months (95 % CI 19.9-not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed. CONCLUSION: First-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients. REGISTRY: UMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E.

Genome-wide linkage and exome analyses identify variants of HMCN1 for splenic epidermoid cyst.

BACKGROUND: Splenic epidermoid cyst is a benign tumor-like lesion affecting the spleen and sometimes occurs in familial form. The causality of such rare diseases remain challenging, however recently, with the emergence of exome re-sequencing, the genetics of many diseases have been unveiled. In the present study, we performed a combinatorial approach of genome-wide parametric linkage and exome analyses for a moderate-sized Japanese family with frequent occurrence of splenic epidermoid cyst to identify the genetic causality of the disease. METHODS: Twelve individuals from the family were subject to SNP typing and exome re-sequencing was done for 8 family members and 4 unrelated patients from Kosovo. Linkage was estimated using multi-point parametric linkage analysis assuming a dominant mode of inheritance. All of the candidate variants from exome analysis were confirmed by direct sequencing. RESULTS: The parametric linkage analysis suggested two loci on 1q and 14q with a maximal LOD score of 2.5 . Exome generated variants were prioritized based on; impact on the protein coding sequence, novelty or rareness in public databases, and position within the linkage loci. This approach identified three variants; variants of HMCN1 and CNTN2 on 1q and a variant of DDHD1 on 14q. The variant of HMCN1 (p.R5205H) showed the best co-segregation in the family after validation with Sanger sequencing. Additionally, rare missense variants (p.A4704V, p.T5004I, and p.H5244Q) were detected in three unrelated Kosovo patients. The identified variants of HMCN1 are on conserved domains, particularly the two variants on calcium-binding epidermal growth factor domain. CONCLUSIONS: The present study, by combining linkage and exome analyses, identified HMCN1 as a genetic causality of splenic epidermoid cyst. Understanding the biology of the disease is a key step toward developing innovative approaches of intervention.

[A case of a patient with advanced rectal cancer and urinary bladder fistula surviving for 6 years after chemoradiotherapy without surgery].

A 60-year-old man with advanced rectal cancer and urinary bladder fistula received preoperative chemoradiotherapy with S-1(120mg/m / 2day)on weekdays and concurrent radiotherapy(65 Gy). After chemoradiotherapy, the clinical symptoms resolved and the tumor shrunk, as observed on endoscopic and radiologic examinations. However, remnant cancer was suspected; therefore, modified oxaliplatin, 5-fluorouracil, and Leucovorin(mFOLFOX6)therapy was initiated, although it was stopped after 3 cycles because of numbness in the lower extremities. Finally, clinical and pathological complete response(CR) was achieved by administering additional doses of S-1 for approximately 1 year after treatment initiation; CR was confirmed by using endoscopy and computed tomography(CT), and there has been no recurrence for 6 years. This case suggests that treatment without surgery is a viable alternative for advanced rectal cancer with pathological CR after chemoradiotherapy.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2010 and March 2011].

Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents - Special references to bacteria isolated between April 2011 and March 2012].

Bacteria isolated from surgical infections during the period from April 2011 to March 2012 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 785 strains including 31 strains of Candida spp. were isolated from 204 (78.8%) of 259 patients with surgical infections. Five hundred and twenty three strains were isolated from primary infections, and 231 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp. and Staphylococcus spp., in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter cloacae, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa, K. pneumoniae, and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Collinsella aerofaciens, Lactobacillus acidophilus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated, followed by P micra and L. acidophilus, in this order. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroidesfragilis was the highest from primary infections, followed by Bilophila wadsworthia, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides vulgatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides caccae, B. thetaiotaomicron, Bacteroides ovatus and B. wadsworthia, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant Staphylococcus aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed. We should carefully follow up B. wadsworthia which was resistant to various antimicrobial agents, and also Bacteroides spp. which was resistant to many ß-lactams.

Detection and genotype of Encephalitozoon cuniculi DNA from urine and feces of pet rabbits in Japan.

A newly developed nested polymerase chain reaction (PCR) assay targeting the internal transcribed spacer (ITS) region of the ribosomal DNA was applied to detect and characterize Encephalitozoon cuniculi DNA from pet rabbits in Japan. The analysis was carried out using 257 urinary samples and 314 fecal samples collected from 307 pet rabbits in the age group of 1 month to 12 years from 30 different prefectures of Japan and 107 fecal samples and 3 urinary samples collected from 1-month-old rabbits from 3 breeding facilities in Japan. We detected 840-bp amplicons in 20 urinary samples (7.78%) from the pet rabbits of the 13 prefectures and in 1 urinary (33.3%) and 6 fecal (5.6%) samples from the rabbits of the 2 breeding facilities. The sequences (803 bp) of the 27 amplicons had no variations and completely coincided with the sequence of E. cuniculi genotype I. To the best of our knowledge, this is the first report on the detection and genotype characterization of E. cuniculi DNA from pet rabbits in Japan.

Chemotherapy with bevacizumab for metastatic colorectal cancer: a retrospective review of 181 Japanese patients.

BACKGROUND: There has so far been little information on the clinical effect of bevacizumab against colorectal cancer in Japan. Hence, this study was conducted to retrospectively evaluate the safety and efficacy of bevacizumab in clinical practice. METHODS: A total of 181 patients with metastatic colorectal cancer (mCRC) received bevacizumab in combination with chemotherapy at 18 hospitals in Kumamoto prefecture, Japan. We surveyed the medical records of all patients regarding the patient characteristics, objective tumor responses, and adverse events. We analyzed their overall survival and the survival benefit when continuing the administration of bevacizumab beyond disease progression (progressive disease; PD) in patients who received bevacizumab-containing 1st line therapy. RESULTS: The response rate (RR) in all lines of therapy was 42 %. The 1st line patients showed significantly better survival in comparison to the patients who received further lines of treatment (P = 0.005). There were no significant differences in survival between the group with post-PD treatment with bevacizumab and the group with post-PD treatment without bevacizumab (P = 0.13). The most common grade 3 or greater adverse event associated with bevacizumab was hypertension (12.2 %). Especially, a high incidence of gastrointestinal (GI) perforation was shown in this study (4.4 %) and most of the patients with GI perforation had some risk factors for this complication. CONCLUSION: Although the survival benefit of bevacizumab in Japanese patients with mCRC was similar to that observed in previous clinical trials, this study showed a high incidence of GI perforation in comparison to previous studies. Therefore, the careful selection of patients with few risk factors for this complication is likely to lead to a greater benefit from bevacizumab treatment.

Prognosis assessment of patients with refractory ascites treated with a peritoneovenous shunt.

BACKGROUND/AIMS: We investigated the postoperative outcome and risk factors for DIC and mortality in cases of implanted PVS. METHODOLOGY: We reviewed the cases of 65 patients implanted with PVS from 2000 to 2010. Of these patients, 32 were diagnosed with peritonitis carcinomatosa, 21 had liver cirrhosis with hepatocellular carcinoma (HCC), and 12 had liver cirrhosis without HCC. RESULTS: The postoperative morbidity rate was 18.8%, 76.2%, and 58.3% in cases of peritonitis carcinomatosa, liver cirrhosis with HCC, and liver cirrhosis without HCC, respectively. Early death (within 7 days of surgery) was 7.7% (5/65), and the cause of death in all cases was DIC. Underlying disease, low platelet count, prolongation of prothrombin time (PT), and hyperbilirubinemia were the risk factors for development of DIC, whereas underlying disease, prolongation of PT, hypoalbuminemia, and hyperbilirubinemia were risk factors for early death. Multivariate analysis showed that liver cirrhosis with HCC and prolonged PT were the risk factors for DIC. CONCLUSIONS: Patients with refractory ascites due to liver cirrhosis with HCC and those with prolonged PT should not be considered for PVS.

[Reduction of vascular pain due to drop-infusion of oxaliplatin (L-OHP) in peripheral vein with heated infusion route].

PURPOSE: The aim of this study is to investigate the possibility of reducting vascular pain with peripheral vein administration of oxaliplatin (L-OHP)by heating infusion routes during XELOX therapy. METHODS: (1) EXPERIMENT: The temperature of the 5%glucose injection solution was measured at the leading edge of the infusion route when it was heated to 36°Cor 40°C. (2) CASES: Among five patients receving XELOX therapy for colorectal cancer, we examined the occurrence of vascular pain by heating the L-OHP solution to 40°C. RESULTS: (1) EXPERIMENT: The injection temperatures were reduced to 25°C and 31°C while passing through the infusion route when L-OHP solution was heated to 36°C and 40°C, respectively. (2) CASE: vascular pain did not occur in all five patients treated with XELOX therapy completely by heating the L-OHP solution at 40°C, including two patients who could not continue treatment caused by vascular pain without the heating method. CONCLUSION: The method using the heat infusion route of L-OHP at 40°C is useful for reducing vascular pain from L-OHP administered intravenously.

Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for previously treated advanced or recurrent gastric cancer.

PURPOSE: NK105 is a new drug delivery system formulation for paclitaxel (PTX) whose recommended dose (RD) is 150 mg PTX equivalent/m(2) administered every 3 weeks, as determined in a phase I trial. This study aimed to evaluate the efficacy and safety of NK105 in patients with advanced gastric cancer after failure of first-line chemotherapy. EXPERIMENTAL DESIGN: Eligible patients had measurable disease and one chemotherapeutic regimen except taxane. NK105 (150 mg PTX equivalent/m(2)) was administered by a 30-minute intravenous infusion every 3 weeks without anti-allergic premedication until disease progression, unacceptable toxicity or patient refusal. The primary efficacy endpoint was best overall response rate (ORR) post baseline. The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS). All adverse events were reported using CTCAE v3.0. RESULTS: Between November 2007 and July 2009, 57 patients were enrolled and 56 were evaluable for efficacy. Two complete responses and 12 partial responses were observed for an ORR of 25%. The median PFS was 3.0 months, the median TTF was 2.8 months, and the median OS was 14.4 months. Drug related toxicity was mainly mild (grades 1-2) to severe (grades 3-4); other data: neutropenia (64.9%); leukopenia (17.5%); lymphopenia (8.8%); neuropathy-sensory (1.8%); fatigue (3.5%); and stomatitis (1.8%). There were no treatment-related deaths. CONCLUSIONS: This study of NK105 (150 mg PTX equivalent/m(2)) proves the concept for the modest activity and tolerability of a new drug delivery system formulation for PTX. A phase III trial will be evaluated to clarify survival benefit.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2009 and March 2010].

Bacteria isolated from surgical infections during the period from April 2009 to March 2010 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 671 strains including 16 strains of Candida spp. were isolated from 174 (79.1%) of 220 patients with surgical infections. Four hundred and eleven strains were isolated from primary infections, and 244 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by Bacteroides fragilis, Bacteroides ovatus and Bacteroides thetaiotaomicron, and from surgical site infection, B. fragilis was most predominantly isolated, followed by B. ovatus, B. wadsworthia and B. thetaiotaomicron, in this order. In this series, we noticed no vancomycin-resistant Gram-positive cocci, nor multidrug-resistant P. aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents --special references to bacteria isolated between April 2008 and March 2009].

Bacteria isolated from infections in abdominal surgery during the period from April 2008 to March 2009 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 712 strains including 18 strains of Candida spp. were isolated from 173 (80.5%) of 215 patients with surgical infections. Three hundred and sixty-six strains were isolated from primary infections, and 346 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from postoperative infections aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from postoperative infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa, in this order, and from postoperative infections, P aeruginosa was most predominantly isolated, followed by E. coli, Enterobacter cloacae, and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Gemella morbillorum, and from postoperative infections, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis was the highest from primary infections, followed by Bacteroides thetaiotaomicron, Bacteroides ovatus and Bilophila wadsworthia, and from postoperative infections, B. fragilis was most predominantly isolated, followed by B. thetaiotaomicron, B. wadsworthia and B. ovatus, in this order. In this series, we noticed no vancomycin-resistant methicillin-resistant S. aureus, and Enterococcus spp., nor multidrug-resistant P aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

[A case of pancreatic cancer treated by gemcitabine with sequential radiotherapy].

A 65-year-old man suffering from acute pancreatitis underwent MRI scanning, which revealed a low signal on the T1 and T2 sequences, and hypovascularity in arterial phase in the head of the pancreas. This corresponded to the area showing the absence of the lower common bile duct. FDG-PET was highly suggestive of pancreatic cancer (T4N1M0, Stage IVa) with lymph node metastasis. He was treated with systemic chemotherapy using gemcitabine (GEM) followed by radiotherapy. His symptoms gradually improved with a reduction in size of the primary lesion. The patient has been receiving systemic chemotherapy using S-1 without recurrence.