Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

Survival impact of surgical site infection in esophageal cancer surgery: A multicenter retrospective cohort study.

Aim: This study was performed to evaluate the oncological impact of surgical site infection (SSI) and pneumonia on long-term outcomes after esophagectomy. Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 407 patients with curative stage I/II/III esophageal cancer at 11 centers from April 2013 to March 2015. We investigated the association of SSI and postoperative pneumonia with oncological outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: Ninety (22.1%), 65 (16.0%), and 22 (5.4%) patients had SSI, pneumonia, and both SSI and pneumonia, respectively. The univariate analysis demonstrated that SSI and pneumonia were associated with worse RFS and OS. In the multivariate analysis, however, only SSI had a significant negative impact on RFS (HR, 1.63; 95% confidence interval, 1.12-2.36; P = 0.010) and OS (HR, 2.06; 95% confidence interval, 1.41-3.01; P < 0.001). The presence of both SSI and pneumonia and the presence of severe SSI had profound negative oncological impacts. Diabetes mellitus and an American Society of Anesthesiologists score of III were independent predictive factors for both SSI and pneumonia. The subgroup analysis showed that three-field lymph node dissection and neoadjuvant therapy canceled out the negative oncological impact of SSI on RFS. Conclusion: Our study demonstrated that SSI, rather than pneumonia, after esophagectomy was associated with impaired oncological outcomes. Further progress in the development of strategies for SSI prevention may improve the quality of care and oncological outcomes in patients undergoing curative esophagectomy.

Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study.

Aim: To investigate the impact of postoperative infection (PI), surgical site infection, and remote infection (RI), on long-term outcomes in patients with colorectal cancer (CRC). Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 1817 curative stage I/II/III CRC patients from April 2013 to March 2015. Patients were divided into the No-PI group and the PI group. We examined the association between PI and oncological outcomes for cancer-specific survival (CSS) and overall survival (OS) using Cox proportional hazards models and propensity score matching. Results: Two hundred and ninety-nine patients (16.5%) had PIs. The 5-year CSS and OS rates in the No-PI and PI groups were 92.8% and 87.6%, and 87.4% and 83.8%, respectively. Both the Cox proportional hazards models and propensity score matching demonstrated a significantly worse prognosis in the PI group than that in the No-PI group for CSS (hazard ratio: 1.60; 95% confidence interval: 1.10-2.34; P = .015 and P = .031, respectively) but not for OS. RI and the PI severity were not associated with oncological outcomes. The presence of PI abolished the survival benefit of adjuvant chemotherapy. Conclusions: These results suggest that PI after curative CRC surgery is associated with impaired oncological outcomes. This survival disadvantage of PI was primarily derived from surgical site infection, not RI, and PI induced lower efficacy of adjuvant chemotherapy. Strategies to prevent PI and implement appropriate postoperative treatment may improve the quality of care and oncological outcomes in patients undergoing curative CRC surgery.

Prognostic impact of postoperative infection in patients with pancreatic cancer: A multicenter cohort study.

BACKGROUND: Postoperative infection after pancreatectomy in patients with pancreatic cancer often leads to poor prognosis. The aim of this study was to determine the prognostic effect of postoperative infection in patients with pancreatic cancer. METHODS: A multicenter cohort study was performed using a common database of patients with pancreatic cancer who underwent curative pancreatic resections between April 2013 and March 2015 at 15 high-volume centers in Japan. The rate of postoperative infection was determined, and patient demographic characteristics, clinicopathologic factors, and prognostic factors for overall survival were analyzed. RESULTS: Of the 462 eligible patients who underwent curative pancreatectomy, postoperative infection occurred in 141 patients (31%), including 114 surgical site infections (25%), 50 remote infections (11%), and 23 combined infections (5%). Risk factors for postoperative infection included high body mass index, nondiabetes, and longer operation time. In the survival analysis, patients with postoperative infection had significantly worse overall survival than patients without postoperative infection. The median survival times were 21.9 and 33.0 months (P = .023), respectively, for patients with and without postoperative infection. According to the multivariate analysis for overall survival, lack of adjuvant therapy (P = .002), but not postoperative infection (P = .829), predicted poor prognosis. The multivariate analysis revealed that postoperative infection (P < .001) was an independent risk factor for lack of adjuvant therapy. CONCLUSION: Postoperative infection in patients with pancreatic cancer may indirectly worsen the prognosis by preventing timely adjuvant therapy.

Change in antimicrobial susceptibility of pathogens isolated from surgical site infections over the past decade in Japanese nation-wide surveillance study.

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum ß-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 µg/mL). By contrast, relatively low geometric mean MICs (0.397 µg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group.

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan.

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum ß-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with ß-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.

Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: Comparison of data from nationwide surveillance studies conducted in 2010 and 2014-2015.

A nationwide survey was conducted in Japan from 2014 to 2015 to investigate the antimicrobial susceptibility of pathogens isolated from surgical site infections (SSI). The resulting data were compared with that obtained in an earlier survey, conducted in 2010. Seven main organisms were collected, and 883 isolates were studied. A significant reduction in methicillin resistance was observed among Staphylococcus aureus isolates, dropping from 72.5% in 2010 to 53.8% in 2014-2015 (p < 0.001). MRSA isolates with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL accounted for 1.2% of all MRSA isolates, which was significantly lower than in 2010 (9.7%, p = 0.029). Of the Escherichia coli isolates, 23.0% produced an extended spectrum ß-lactamase (ESBL) in the 2014-2015 survey, which was a significant increase from 9.5% in 2010 (p = 0.011). The geometric mean MICs for ESBL-producing isolates were 0.07 µg/mL for meropenem, 9.51 µg/mL for tazobactam/piperacillin, 0.15 µg/mL for flomoxef, and 1.56 µg/mL for gentamycin. There was a significant increase in the isolation rate of non-fragilis Bacteroides among Bacteroides fragilis group species between the two study periods (35.2% vs. 53.1%, p = 0.007). More than 90% of isolates belonging to the B. fragilis group remained susceptible to tazobactam/piperacillin, meropenem, and metronidazole. In contrast, lower levels of susceptibility were observed for cefmetazole (49.6%), moxifloxacin (61.9%), and clindamycin (46.9%). Non-fragilis Bacteroides isolates had lower rates of antibiotic susceptibility compared with B. fragilis. Overall, the surveillance data clarified trends in antimicrobial susceptibility for organisms commonly associated with SSI.

[A case of advanced gastric cancer with multiple liver metastases completely responding long term to paclitaxel plus S-1 therapy].

A 69-year-old man was admitted to our hospital with complaints of loss of appetite, fatigue and dysphasia. Upper gastroscopy revealed advanced gastric cancer. Abdominal CT suggested liver metastases. At first we thought the liver metastases has been completely resected, but we found multiple liver metastases unexpectedly. So only total gastric resection and liver biopsy were performed. The pathological diagnosis was metastatic carcinoma. Paclitaxel (PTX) and S-1 combination chemotherapy was started after operation and was continued for 42 courses. A CT scan showed a complete response, and he has been well without tumor re-growth ever since. The combination of PTX and S-1 not only may be an effective regimen for gastric cancer with liver metastases, but also can be used without side effects for a long time.

Development of a surgical site infection (SSI) surveillance system, calculation of SSI rates and specification of important factors affecting SSI in a digestive organ surgical department.

We have developed an original system to conduct surgical site infection (SSI) surveillance. This system accumulates SSI surveillance information based on the National Nosocomial Infections Surveillance (NNIS) System and the Japanese Nosocomial Infections Surveillance (JNIS) System. The features of this system are as follows: easy input of data, high generality, data accuracy, SSI rate by operative procedure and risk index category (RIC) can be promptly calculated and compared with the current NNIS SSI rate, and the SSI rates and accumulated data can be exported electronically. Using this system, we monitored 798 patients in 24 operative procedure categories in the Digestive Organs Surgery Department of Mazda Hospital, Mazda Motor Corporation, from January 2004 through December 2005. The total number and rate of SSI were 47 and 5.89%, respectively. The SSI rates of 777 patients were calculated based on 15 operative procedure categories and Risk Index Categories (RIC). The highest SSI rate was observed in the rectum surgery of RIC 1 (30%), followed by the colon surgery of RIC3 (28.57%). About 30% of the isolated infecting bacteria were Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Using quantification theory type 2, the American Society of Anesthesiology score (4.531), volume of hemorrhage under operation (3.075), wound classification (1.76), operation time (1.352), and history of diabetes (0.989) increased to higher ranks as factors for SSI. Therefore, we evaluated this system as a useful tool in safety control for operative procedures.

[Prophylactic effect of fosfomycin on postoperative infection in gastroenterological surgery].

Fosfomycin (FOM), a drug with unique mechanism of action against bacteria, was prospectively compared with cefmetazole (CMZ) and flomoxef (FMOX) to assess its effectiveness in preventing postoperative infections after upper gastroenterological and hepatobiliary surgery. FOM (2g/dose), CMZ (1 g/dose), or FMOX (lg/dose) was infused intravenously 2-3 times daily for basically 4 days including the day of surgery in order to examine whether or not infections would develop after surgery. According to the analysis results of 162 cases, efficacy in preventing infection was 86.8% for FOM, 73.1% for CMZ and 83.3% for FMOX, showing no significant differences among the 3 groups. Thus FOM was considered as efficacious as CMZ or FMOX in prophylaxis against postoperative infections. There were no adverse reactions in the FOM or CMZ group, but 3 cases of adverse reactions occurred in the FMOX group. Based on the above results, the usefulness of FOM for prophylaxis against postoperative infections has been confirmed. At present, the first- and second-generation cephems are most frequently used for prophylaxis against postoperative infections. In order to prevent an increase of resistant strains due to inappropriate use of these drugs, FOM, having no cross resistance with currently used drugs, is a promising candidate for prophylaxis against postoperative infections.

Changes in the intestinal flora after the administration of prophylactic antibiotics to patients undergoing a gastrectomy.

PURPOSE: Changes in the intestinal flora were investigated in patients administered antibiotics for 4 days after a gastrectomy. METHODS: Twenty-four patients were divided into each of the following groups: cefazolin, 1 g every 8 h; cefozopran, 0.5 g every 8 h; flomoxef, 1 g every 8 h. All drugs were administered intravenously for a 4-day period. RESULTS: Antibiotic prophylaxis caused no major change in the total number of anaerobes because of the preservation of the Bacteroides fragilis group. However, the number of Bifidobacterium, Lactobacillus, Eubacterium, and Veillonella spp. decreased by an average of 100-fold. These changes were accompanied by an overgrowth of Enterococcus spp. and Pseudomonas aeruginosa. CONCLUSIONS: Four days of antibiotic prophylaxis after surgery caused a suppression of colonization resistance in the intestinal flora. Certain genera of anaerobes may thus play an important role in preventing overgrowth of antibiotic-resistant organisms after surgery. Surgeons should decide the duration of antibiotic use after carefully considering its influence on the intestinal flora.

Changes in intestinal flora after administration of panipenem/betamipron or sulbactam/cefoperazone for treatment of postoperative infections in gastrectomy patients.

To determine the effect of antibiotics used for the treatment of postoperative infections on the normal intestinal flora in patients who have undergone gastroenterological surgery, we performed a prospective randomized study in patients who had undergone distal gastrectomy. Cefazoline was administered up to postoperative day 3 for prophylaxis. For the treatment of postoperative infections, either panipenem/betamipron (PAPM/BP; n = 5) or sulbactam/cefoperazone (SBT/CPZ; n = 5) was adminstered to ten patients with signs of postoperative infections. Feces were examined for bacteria before and 4 and 7 days after the commencement of administration of these therapeutic antibiotics. The anaerobic bacterial count decreased significantly in four of five patients treated with SBT/CPZ, from 1010.2+/-0.36/g before treatment to 105.22+/-3.51/g. In the PAPM/BP-treated group, the anaerobic bacterial count did not change after antibiotic therapy. We also investigated the major genera of colonic anaerobes, and found that the numbers of bifidobacteria were maintained during PAPM/BP administration. However, in the SBT/CPZ group, the number of bifidobacteria decreased to below the detection limit in four of five patients. Little change was observed in the aerobic bacterial count in either group. However, Enterobacteriaceae were replaced by enterococcus or candida in all patients from the SBT/CPZ group and in one of five patients from the PAPM/BP group. Physicians should be alert for the possible clinical consequences of changes in intestinal microflora after antibiotic treatment of postoperative infections.