External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

BACKGROUND: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. METHODS: The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. RESULTS: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. CONCLUSION: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Time required for indocyanine green fluorescence emission for evaluating bowel perfusion in left-sided colon and rectal cancer surgery.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) has been reported to be useful in reducing the incidence of anastomotic leakage (AL) in colectomy. This study aimed to investigate the correlation between the required time for ICG fluorescence emission and AL in left-sided colon and rectal cancer surgery using the double-stapling technique (DST) anastomosis. METHODS: This retrospective study included 217 patients with colorectal cancer who underwent left-sided colon and rectal surgery using ICG-FI-based perfusion assessment at our department between November 2018 and July 2022. We recorded the time required to achieve maximum fluorescence emission after ICG systemic injection and assessed its correlation with the occurrence of AL. RESULTS: Among 217 patients, AL occurred in 21 patients (9.7%). The median time from ICG administration to maximum fluorescence emission was 32 s (range 25-58 s) in the AL group and 28 s (range 10-45 s) in the non-AL group (p < 0.001). The cut-off value for the presence of AL obtained from the ROC curve was 31 s. In 58 patients with a required time for ICG fluorescence of 31 s or longer, the following risk factors for AL were identified: low preoperative albumin [3.4 mg/dl (range 2.6-4.4) vs. 3.9 mg/dl (range 2.6-4.9), p = 0.016], absence of preoperative mechanical bowel preparation (53.8% vs. 91.1%, p = 0.005), obstructive tumor (61.5% vs. 17.8%, p = 0.004), and larger tumor diameter [65 mm (range 40-90) vs. 35 mm (range 4.0-100), p < 0.001]. CONCLUSION: The time required for ICG fluorescence emission was associated with AL.

Utility of Robot-assisted Laparoscopic Transabdominal Preperitoneal Repair of Inguinal Hernia Following Robot-assisted Laparoscopic Radical Prostatectomy.

BACKGROUND: To evaluate the utility of robot-assisted laparoscopic transabdominal preperitoneal repair (R-TAPP) of postprostatectomy inguinal hernia (PIH) in patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP). PATIENTS AND METHODS: This was a prospective, single-centre retrospective cohort study. R-TAPP was conducted in 74 consecutive patients from September 2016 to March 2020. With the exception of women and patients who underwent previous abdominal surgery, 70 patients were classified into two groups based on the absence or presence of PIH. Their data were retrospectively compared to those who had not undergone RALP. RESULTS: The median operative time for the PIH group was longer compared to the non-PIH group. However, postoperative complications, including seroma formation, haematoma and surgical site infections, were not significantly different between the groups. The estimated blood loss was small, and hospitalisation duration was 1 day in all cases. Moreover, there were no hernia recurrences within the 90-day follow-up period in either group. CONCLUSION: R-TAPP is a feasible and safe approach for inguinal hernia repair, even in patients who undergo RALP for prostate cancer.

Utility of Concurrent Surgical Treatment Strategy with Thoracoscopic Esophagectomy for Patients with Synchronous Esophageal and Head and Neck Cancer.

Background: Patients with esophageal squamous cell cancer (ESCC) have a high frequency to coincide with head and neck cancer (HNC). This study aims to analyze the treatment results and prognosis of patients with synchronous ESCC and HNC. Methods: From January 2016 to December 2019, 5 patients underwent concurrent surgical resection of synchronous ESCC and HNC in our institution. We retrospectively reviewed the surgical outcomes and prognosis of these patients with synchronous ESCC and HNC (HNEC group) and compared the results with those of 20 patients who underwent esophagectomy with three regional lymph node dissections for ESCC during the same period (EC group). Results: The locations of HNCs were pharynx/tongue (4/1) and the clinical stages were Stage IV in all patients. Meanwhile, the clinical stages of ESCCs were Stages 0/I/II/III (1/1/2/1). All patients underwent thoracoscopic esophagectomy. The surgical procedures concurrently performed for HNC were pharyngolaryngectomy with free jejunum transfer in 3 patients, wide tongue and mandibular segment resection with mandibular reconstruction in 1 patient, and mandibular transection with radial forearm flap reconstruction in 1 patient. There was no significant difference in the frequency of postoperative complication between these two groups. The HNEC group had a significantly shorter recurrence-free survival than the EC group (P = .046). Conclusion: Head and neck surgery with thoracoscopic esophagectomy can be safely performed concurrently with local control. The risk of recurrence is higher in ESCC patients with HNC; therefore, it is important to move on to adjuvant therapy without delay.

Laparoscopic low anterior resection for rectal cancer associated with Leriche syndrome: a case report.

A 78-year-old male presented with a positive fecal occult blood test. Rectal cancer was detected during lower gastrointestinal endoscopy, and further investigations led to a diagnosis of cT1N0M0 cStage I (UICC classification, 8th edition). Preoperative contrast-enhanced computed tomography (CT) showed that the patient also had Leriche syndrome, which is associated with reduced blood flow to the rectum that may result in ischemic anastomosis during rectal cancer surgery with anastomotic reconstruction. The inferior epigastric arteries often function as collateral pathways to the lower limbs in patients with Leriche syndrome; therefore, care is needed to avoid vascular damage during trocar insertion when performing laparoscopic surgeries. We herein described a case of safe laparoscopic low anterior resection in a rectal cancer patient with Leriche syndrome using vascular architecture images obtained by preoperative CT angiography.

Survey on the current status of the indication and implementation protocols for bile replacement in patients with external biliary drainage with special reference to infection control.

PURPOSE: This survey of bile replacement (BR) was conducted on patients with external biliary drainage to assess the current status of indication and implementation protocol of BR with special reference to infection control. METHODS: A 12-item questionnaire regarding the performance of perioperative BR was sent to 124 institutions in Japan. RESULTS: BR was performed in 29 institutions, and the indication protocol was introduced in 19. BR was performed preoperatively in 11 institutions, pre- and postoperatively in 12, and postoperatively in 6. The methods used for BR administration included oral intake (n = 10), nasogastric tube (n = 1), enteral nutrition tube (n = 3), oral intake and enteral nutrition tube (n = 6), oral intake or nasogastric tube (n = 2), nasogastric tube and enteral nutrition tube (n = 2), and oral intake or nasogastric tube and enteral nutrition tube (n = 5). In 10 of 29 institutions, isolation of multidrug-resistant organisms and a high bacterial load were considered contraindications for the use of BR. Seven institutions experienced environmental contamination. CONCLUSIONS: Given the different implementation of BR among institutions, the appropriate indication and protocols for BR should be established for infection control.

Individualization of the infusion rate of a soybean oil-based intravenous lipid emulsion for inpatients, based on baseline triglyceride concentrations: A population pharmacokinetic approach.

BACKGROUND: A rapid infusion rate for intravenous lipid emulsion (ILE) can cause adverse effects; therefore, safe and efficient infusion rates are desired. This study aimed to develop a triglyceride (TG) kinetic model after soybean oil-based ILE (SO-ILE) administration and individualize the infusion rate via a population pharmacokinetic approach. METHODS: Eighty-three inpatients were enrolled in this prospective observational study. A TG kinetic model was applied to the observations based on population pharmacokinetics using a nonlinear mixed-effect model. The patients' characteristics and laboratory parameters were evaluated to identify predictors of TG kinetics, and the maximum acceptable infusion rate was defined as that for which the maximum TG concentration did not exceed 400 mg/dl in 90% of patients. RESULTS: No adverse events associated with SO-ILE administration were observed. The developed TG kinetic model explained the observed TG concentrations and identified the baseline TG concentration and body weight as predictors of TG kinetics. The estimated maximum acceptable infusion rates greatly varied among individuals, ranging from <0.01 to 0.3 g/kg/h. CONCLUSION: The present study suggested the necessity and demonstrated the feasibility of individualizing the infusion rates of SO-ILE, using a population pharmacokinetic approach.

Clinical practice guidelines for rehabilitation nutrition in cerebrovascular disease, hip fracture, cancer, and acute illness: 2020 update.

BACKGROUND: Individuals undergoing rehabilitation often experience nutritional problems such as malnutrition, but there are no clinical practice guidelines (CPGs) specifically tailored to the combination of rehabilitation and nutritional care for these patients. The Japanese Association for Rehabilitation Nutrition aimed to develop CPGs for rehabilitation nutrition to support clinical decision making in daily practice. METHODS: A CPG committee and development process based on the Grading of Recommendations Assessment, Development and Evaluation system and the Minds Handbook for Clinical Practice Guideline Development 2014 was established. Four clinical questions were defined for patients undergoing rehabilitation for cerebrovascular disease, hip fracture, cancer, and acute illness. Literatures of randomised control trials (RCTs) up to April 2020 were searched for using the MEDLINE, EMBASE, CENTRAL, and Ichushi-web databases. After screening, full-text papers were assessed for eligibility for analysis. Subsequently, studies included in the systematic review were examined regarding their risk of bias, and underwent meta-analyses. A CPG development committee drafted the guidelines based on the systematic review report. Final recommendations were determined by the panel members. RESULTS: Four recommendations were made based on 4 to 9 RCTs for each disease/condition. The certainty of the evidence ranged from very low to low. Overall, the enhanced nutritional care was weakly recommended for rehabilitation patients with cerebrovascular disease, hip fracture, cancer, and acute illnesses. CONCLUSIONS: This CPG provides tentative recommendations for nutritional care of individuals undergoing rehabilitation. Due to low certainty of evidence and small sample sizes of the included studies, more high-quality and larger RCTs are needed to develop more practical CPGs.

Evaluation of accuracy of laparoscopic liver mono-segmentectomy using the Glissonian approach with indocyanine green fluorescence negative staining by comparing estimated and actual resection volumes: A single-center retrospective cohort study.

BACKGROUND/PURPOSE: Laparoscopic liver mono-segmentectomy (LLMS) may improve patient outcomes, but it is difficult and its accuracy and safety are unknown. We evaluated the accuracy of LLMS using Glissonian approach with indocyanine green fluorescence (ICG) negative staining. METHODS: Seventy-four patients eligible for LLMS except for segment 1 were enrolled. Preoperative three-dimensional CT-based surgical simulation was used to determine estimated liver resection volume (ELRV), which was compared with modified actual liver resection volume (ALRV) obtained from actual liver resection mass. The LLMS accuracy was also evaluated based on operator's experience (attending surgeon [AS] or trainee surgeon [TS]). RESULTS: Estimated liver resection volumes significantly correlated with ALRVs (r = .82) in all cases. Moreover, TS-conducted LLMS also showed acceptable difference between ELRV and ALRV compared with AS-conducted LLMS. There were no intergroup differences in estimated blood loss, operation time, time of Pringle maneuver, postoperative complications, and length of postoperative hospitalization (P < .05). Moreover, R0 resection was comparable between the AS and TS groups. CONCLUSIONS: Laparoscopic liver mono-segmentectomy with Glissonian approach using ICG negative imaging ensured safe and accurate procedure owing to facilitated visualization of the resection line. Our approach was effective in avoiding postoperative liver dysfunction and securing radical resection. In addition, it might be helpful in TS education of LLMS.

Pure Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus (with Video).

BACKGROUND: Laparoscopic liver resection has been increasingly utilized due to its less invasiveness approach compared with open surgery,1-3 but often creates challenges. Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) portends a poorer prognosis and often precludes patients from potential liver resection.4-6 We herein report a case of laparoscopic hepatectomy and thrombectomy in a patient with HCC and BDTT. METHODS: CT, ERCP, and POCS showed a 40-mm tumor located in the right lobe with BDTT. A five 12-mm trocar was inserted at the umbilicus for laparoscope, the epigastrium, both sides of the hypochondrium, and right lateral region. Moreover, a 5-mm trocar was inserted at left hypochondrium. After cholecystectomy, hepatoduodenal ligament was encircled using the tourniquet through 5-mm trocar site. The right portal vein was transected by stapler following transection of the right hepatic artery. After ICG staining (0.5 mg/body i.v.),7 hepatic parenchymal transection was performed using clamp-crashing technique. Moreover, CUSA also was used near Glissonian sheath. BDTT was removed from the right BD. Moreover, the cholangioscopy confirmed no BDTT remnants. The resection stump was then sutured. Finally, the right hepatic vein was divided with a stapler. A drainage tube was placed in the right subphrenic space. Operation time was 496 min, and blood loss was 91 ml. The patient was discharged without complications on postoperative day 11. Pathological diagnosis showed moderately differentiated HCC, tumor size 40 × 45 mm with negative surgical margins. CONCLUSIONS: Pure laparoscopic resection for HCC with BDTT is a radical, yet feasible procedure.

Geriatric Nutritional Risk Index Less Than 92 Is a Predictor for Late Postpancreatectomy Hemorrhage Following Pancreatoduodenectomy: A Retrospective Cohort Study.

Postpancreatectomy hemorrhage (PPH) is the most lethal complication of pancreatoduodenectomy (PD). The main risk factor for PPH is the development of a postoperative pancreatic fistula (POPF). Recent evidence shows that the geriatric nutritional risk index (GNRI) may be predictive indicator for POPF. In this study, we aimed to evaluate whether GNRI is a reliable predictive marker for PPH following PD. The present study retrospectively evaluated 121 patients treated with PD at Ageo Central General Hospital in Japan between January 2015 and March 2020. We investigated the potential of age, gender, body mass index, serum albumin, American Society of Anesthesiologists classification (ASA), diabetes mellitus and smoking status, time taken for the operation, estimated blood loss, and postoperative complications (POPF, bile leak, and surgical site infections) to predict the risk of PPH following PD using univariate and multivariate analyses. Ten patients had developed PPH with an incidence of 8.3%. Among them, the patients were divided into bleeding group (n = 10) and non-bleeding group (n = 111). The bleeding group had significantly lower GNRI values than those in the non-bleeding group (p = 0.001). We determined that the cut-off value of GNRI was 92 accounting for a sensitivity 80.0%, specificity 82.9%, and likelihood ratio of 4.6 using receiver operating characteristic curve analysis. A GNRI of <92 was statistically associated with PPH in both univariate (p < 0.001) and multivariate analysis (p = 0.01). Therefore, we could identify that a GNRI < 92 was an independently potential predictor of PPH risk following PD. We should alert surgeons if patients have low level GNRI before PD.

[Laparoscopic Hepatic Resection for a Hepatic Perivascular Epithelioid Cell Tumor-A Case Report].

A 50-year-old female who had a liver tumor was referred to our hospital for further examination. Abdominal CT and MRI revealed a 2 cm tumor in liver segment 2 that was suspected to be HCC. On the basis of the CT and MRI findings, the patient underwent needle biopsy. The pathological findings suggested the possibility of perivascular epithelioid cell tumor (PEComa). Accordingly, we performed laparoscopic liver segmentectomy. As a hepatic PEComa is relatively rare, the current case serves as an important reminder to consider PEComa in the differential diagnosis of liver tumors.

Geriatric nutritional risk index serves as risk factor of surgical site infection after pancreatoduodenectomy: a validation cohort Ageo study.

BACKGROUND: Surgical site infections (SSIs), which are associated with preoperative malnutrition, are a well-known potential complication of surgery that leads to increased medical costs and longer hospitalizations. Thus, surgeons need to accurately identify patients at high-risk for SSIs. Considering that the Geriatric Nutritional Risk Index (GNRI) was designed to assess the degree of malnutrition specifically among elderly patients, previous evidence (Kawaguchi study) proved that GNRI predicted the risk of SSIs in patients following pancreatoduodenectomy (PD). In this study, we aimed to validate whether that the same index could predict the risk of SSI among patients who underwent PD in our patient cohort (Ageo study). METHODS: The current validation cohort study was retrospectively conducted on 93 patients at the Department of Surgery, Ageo Central General Hospital, Japan, from January 2015 to October 2019. All patients were subjected to nutritional screening using the GNRI and were followed up for the occurrence of postoperative complications. Additionally, risk factors for developing SSI, as well as patient's height, body mass index, and preoperative laboratory values, were recorded. RESULTS: Patients were divided into the SSI (N=30) and non-SSI (N=63) groups with a determined SSI incidence rate of 32.3% (30/93). The SSI group had significantly lower GNRI than the non-SSI group (P<0.001). Receiver operating characteristic curve analysis determined a cutoff GNRI value of 94 (sensitivity, 83.3%; specificity, 83.6%), similar to that in the previous study. Univariate and multivariate analyses confirmed that a GNRI of <94 was significantly associated with SSI (P<0.001). CONCLUSIONS: The present Ageo study confirmed the consistency of results in Kawaguchi study. Thus, lower GNRI can be a universal marker for SSI risk following PD.

Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).

BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

Measuring body composition using the bioelectrical impedance method can predict the outcomes of gemcitabine-based chemotherapy in patients with pancreatobiliary tract cancer.

In order to examine the effect on body composition of anticancer drug treatments, the body composition rate in patients being treated with gemcitabine (GEM)-based chemotherapy was measured over time on an outpatient basis with a simple body composition monitor using the bioelectrical impedance (BI) method. The results revealed a significant reduction in the body fat rate (P=0.01) over the course of treatment in patients with pancreatobiliary tract cancer who became unable to continue GEM-based chemotherapy due to progressive disease or a decreased performance status. Meanwhile, no changes were observed in the body composition of control patients with urothelial carcinoma receiving GEM-based chemotherapy. In association with the adverse reactions to GEM and the hematotoxicity profile, a decreased white blood cell count was more likely to occur in body fat-dominant patients (mean fat rate, 25.8%; mean muscle rate, 26.2%), whereas a decreased blood platelet count was more likely to occur in skeletal muscle-dominant patients (mean fat rate, 23.3%; mean muscle rates, 28.7%). The correlation between body composition parameters and the relative dose intensity (RDI) associated with GEM administration was also analyzed. The results revealed a positive correlation between the RDI and basal metabolism amount (P=0.03); however, the RDI did not correlate with the body fat rate, skeletal muscle rate or body mass index (P=0.61, P=0.14 and P=0.20, respectively). In conclusion, the body composition rate measurement using the BI method over time may be useful for predicting the outcome of GEM-based chemotherapy and adverse events in patients with pancreatobiliary tract cancer. In particular, the present findings indicate that the changes in body fat rate may be helpful as an adjunct index for assessing potential continuation of chemotherapy and changes in physical conditions.

Nationwide surveillance of antimicrobial susceptibility patterns of pathogens isolated from surgical site infections (SSI) in Japan.

To investigate the trends of antimicrobial resistance in pathogens isolated from surgical site infections (SSI), a Japanese surveillance committee conducted the first nationwide survey. Seven main organisms were collected from SSI at 27 medical centers in 2010 and were shipped to a central laboratory for antimicrobial susceptibility testing. A total of 702 isolates from 586 patients with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4 %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among S. aureus was 72.0 %. Vancomycin MIC 2 µg/ml strains accounted for 9.7 %. In Escherichia coli, 11 of 95 strains produced extended-spectrum ß-lactamase (Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains produced metallo-ß-lactamase. In P. aeruginosa, the resistance rates were 7.4 % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group, the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and IPM, and 0 % to metronidazole (Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0 %). MIC90 of P. aeruginosa isolated 15 days or later after surgery rose in TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of Anesthesiologists (ASA) score ≥3, the resistance rates of P. aeruginosa to TAZ/PIPC and CAZ were higher than in patients with ASA ≤2. The data obtained in this study revealed the trend of the spread of resistance among common species that cause SSI. Timing of isolation from surgery and the patient's physical status affected the selection of resistant organisms.

Phase II study of weekly paclitaxel, cisplatin, and 5-fluorouracil for advanced gastric cancer.

BACKGROUND: Our previous phase I study provided evidence that weekly paclitaxel, cisplatin, and bolus 5-fluorouracil (weekly PCF) was effective and well tolerated in patients with advanced gastric cancer. This study was conducted to confirm the efficacy and toxicity of weekly PCF. METHODS: Eligibility criteria were as follows: pathological confirmation; measurable lesion(s); and no history of treatment with taxanes, platinum-based compounds, or intravenous 5-fluorouracil (1 regimen of pre-treatment with oral 5-fluorouracil agents was allowed). Paclitaxel (80 mg/m(2), 1 h), cisplatin (25 mg/m(2), 2 h), and 5-fluorouracil (600 mg/m(2), bolus) were administered on days 1, 8, and 15, every 4 weeks. RESULTS: Between March 2006 and May 2009, 46 patients were enrolled and 45 were assessed. Eighteen had a history of pre-treatment with oral 5-fluorouracil agents. The response rate was 56% [95% confidence interval (CI) 41-70%]. Median progression-free survival was 160 days (95% CI 145-214 days). Median overall survival was 552 days (95% CI 350-843 days). Grade 3-4 major adverse reactions observed were neutropenia (76%), leucopenia (38%), anaemia (27%), febrile neutropenia (22%), exacerbation of performance status (16%), and anorexia (13%). CONCLUSION: A weekly PCF regimen is promising for advanced gastric cancer, although it is associated with moderate hematological and minimal non-hematological toxicities.

[Points in nutritional management of the elderly].

The most important aim of nutritional management in the elderly is to maintain the strength of skeletal muscle and ability to perform activities of daily living (ADL). The total energy expenditure (TEE) decreases with age and accelerates after the age of 65 years. Impaired glucose tolerance becomes progressively more common with advancing age. On the other hand, healthy elderly people have a capacity similar to that of healthy young people to clear and oxidize a triacylglycerol load. Consequently, fat appears to be a more suitable fuel for the elderly than glucose. It is recommended that the elderly have a higher protein intake compared with young adults to maintain skeletal muscle. The TEE of the elderly is 20-25 kcal/kg/day, and the recommended daily allowance of protein is 1.0-12 g/kg/day. Furthermore, the ratio of fat in nonprotein calories should be the same as that for young adults. Eating fruit and vegetables can prevent the development of cancer. However, most elderly individuals do not take the time to prepare and eat fruit and vegetables regularly. Elderly people whose ability to perform ADL is impaired should undergo rehabilitation. Unnecessary rest should be avoided during inpatient rehabilitation. Impairment of the ability to perform ADL due to iatrogenic factors or an inappropriate understanding of the elderly metabolism must be avoided.

Changes in bowel mucosal permeability and wound healing after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is a promising approach for locally advanced gastric cancer. We investigated the influence of NAC with 5-FU/CDDP on the permeability of intestinal mucosa and wound healing. Male Sprague Dawley rats were divided into four groups (n=6). Group 1 received saline (control group) and Groups 2-4 were administered preoperative 5-FU/CDDP (NAC groups). The NAC consisted of daily intraperitoneal administration of 5-FU from day 1 to 5 and from day 8 to 12 and intravenous administration of CDDP on days 2 and 9. The rats underwent gastrotomy (1.0 cm) with a laparotomy of 3 cm in length, under general anesthesia. Seven days after surgery, the rats were orally administered with phenolsulfonphthalein (PSP), and the 24-h urinary excretion of PSP was quantified. On postoperative day 8, the bursting pressure (BP) of the gastric suture line and the tensile strength of the abdominal wound were measured. The hydroxyproline (HP) content in the tissue of the abdominal suture line was then measured, and the number of fibroblast cells in the tissue of the gastric suture line was calculated by histopathological examination. The PSP urinary excretion rate was significantly higher in Group 2 in comparison with the other groups (P<0.05), while the BP of a selected gastrorrhaphy region was significantly lower in Group 2 (P<0.05). No significant differences were noted in the HP content. NAC with 5-FU/CDDP disturbs the healing of intestinal anastomoses when the interval between chemotherapy and surgery is insufficient. Neither HP content nor fibroblast counts were correlated with BP. Consequently, NAC appeared to affect the remodeling of collagen fiber. Thus, the integrity of the intestine may play a role in intestinal wound healing.

Urinary metabolic profile of phenylketonuria in patients receiving total parenteral nutrition and medication.

Nutrition and drugs are main environmental factors that affect metabolism. We performed metabolomics of urine from an 8-year-old patient (case 1) with epilepsy and an 11-year-old patient (case 2) with malignant lymphoma who was being treated with methotrexate. Both patients were receiving total parenteral nutrition (TPN). We used our diagnostic procedure consisting of urease pretreatment, partial adoption of stable isotope dilution, gas chromatography/mass spectrometry (GC/MS) measurement and target analysis for 200 analytes including organic acids and amino acids. Surprisingly, their metabolic profiles were identical to that of phenylketonuria. The neopterin level was markedly above normal in case 1, and both neopterin and biopterin were significantly above normal in case 2. Mutation analysis of genomic DNA from case 1 showed neither homozygosity nor heterozygosity for phenylalanine hydroxylase deficiency. The metabolic profiles of both cases were normal when they were not receiving TPN. TPN is presently prohibited for individuals who have inherited disorders that affect amino acid metabolism. Although the Phe content of the TPN was not the sole cause of the PKU profile, its effect, combined with other factors, e.g. specific medication or possibly underlying diseases, led to this metabolic abnormality. The present study suggests that GC/MS-based metabolomics by target analysis could be important for assuring the safety of the treatments for patients receiving both TPN and methotrexate. Metabolomic profiling, both before and during TPN, is useful for determining the optimal nutritional formula not only for neonates, but also for young children who are known heterozygotes for metabolic disorders or whose status is unknown.