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.

Role of Surgery in the Management for Gastric Cancer with Synchronous Distant Metastases.

Optimal treatment of patients with gastric cancer with synchronous distant metastases is palliative chemotherapy. However, occasionally gastrectomy should be selected due to control bleeding from tumors, perforation, or obstruction. The aim of this study is to evaluate the survival benefits of non-curative gastrectomy for patients with synchronous distant metastasis. Total 78 gastric cancer patients with synchronous distant metastasis treated in our hospital between 2003 and 2012 were enrolled in this study. Of these, 74 patients (95 %) received S1 based chemotherapy. During the treatment, 37 patients (47.4 %) underwent palliative gastrectomy because of bleeding from tumors (n = 15), tumor perforation (n = 6), and obstruction (n = 16). Survival benefits were compared in resected and non-resected patients, retrospectively. The two groups were clinicopathologically similar. Palliative gastrectomy was performed safely (morbidity: 10.8 % and mortality: 0) in resection group. However, resection showed survival benefits only in 13 patients (16.7 %) with single metastasis and without peritoneal metastasis. Their 2-year survival rate was 40 % and their median survival was 19 months. Non-curative gastrectomy with precise surgical techniques followed careful postoperative nutrition management may improve survival only for patients with a single metastatic site, except for peritoneal dissemination.

Changes in Standard Treatments and Postoperative Outcomes for Advanced Gastric Cancer at One Institute over an 11-Year Period.

BACKGROUND: Reportedly, the recently established postoperative adjuvant chemotherapies (ADJs) with tegafur and uracil (UFT) or fluoropyrimidine S (S-1) show better survival than surgery alone in patients with advanced gastric cancer (GC). We analyzed chronological changes in postoperative prognosis of patients with advanced GC in our institute, and investigated the efficacy of ADJ in patients with stage II-III GC. METHODS: Of 143 patients with stage II-III GC who underwent curative gastrectomy at Tottori University Hospital between 1998 and 2008, three died with operative complications within 1 month after surgery. The remaining 140 patients were followed to the end of 2013. We compared disease-free survival (DFS) and clinicopathological differences between 82 patients who underwent gastrectomy during 1998-2002 (Group A) and 58 patients who underwent gastrectomy during 2003-2008 (Group B). RESULTS: Operative quality, as represented by number of dissected lymph nodes, was similar in both groups, but the recurrence rate of Group A (51.2%) was higher than in Group B (37.9%, P = 0.12) and the 5-year DFS rate of Group B (62.3%) was higher than that of Group A (50.2%, P = 0.095). In stage II, the 5-year DFS rate of patients in Group B (73.3%) was similar to Group A (77%), but at tumor stage III, the 5-year DFS rate of patients in Group B increased to 48.7%, compared with 33.1% of Group A. Between 2003 and 2008, S-1 was widely used as ADJ for stage II-III GC. CONCLUSION: Postoperative ADJ with S-1 improved DFS of patients with stage III gastric cancer.

Surgical treatment of retroperitoneal liposarcoma.

BACKGROUND: Retroperitoneal liposarcoma (RL) is a relatively rare tumor and is usually found at the advanced stage. Chemotherapy or radiotherapy for this tumor is not yet defined, and if operable, surgery is the treatment of choice. Complete resection of tumor with wide margins including excision of other organs has been recommended. However, many patients suffer from deterioration of the quality of a postoperative life. In the present study, we retrospectively analyzed the ideal surgical procedures for treating RL. METHODS: RL patients treated at our institute between 2003 and 2013 amounted to 10. RL was primary in 5 patients and recurrent in the rest 5. We analyzed cases of the 10 patients retrospectively. RESULTS: Tumor resection was performed for 9 patients, 7 of whom underwent complete tumor resection. RL was well-differentiated in 6 patients and dedifferentiated in 4. We analyzed the overall survival of 10 patients, and the relapse free survival of the operated 9 patients. Patients with well-differentiated RL showed better survival than those with dedifferentiated RL. Even the recurrent RL was huge, complete tumor resection could be performed in the well-differentiated type, but it was difficult in the dedifferentiated type. CONCLUSION: In the recurrent huge RL, the chance of a margin-negative resection remains low, but surgery remains the treatment of choice. Tumor resection with preserving important organs may improve patients' quality of postoperative life and survival.

Clinicopathologic characteristics and prognosis of advanced gastric cancer simulating early gastric cancer.

BACKGROUND: Although the clinicopathologic features and prognosis of Borrmann type advanced gastric cancer has been well characterized, those of advanced gastric cancer simulating early gastric cancer (AGC simulating EGC) still remains unclear. METHODS: We reviewed 1985 gastric cancer patients who had undergone gastrectomy at our hospital to determine the clinicopathologic characteristics, susceptible sites for lymph node metastasis, and prognosis of AGC simulating EGC in comparison with Borrmann type advanced gastric cancer. RESULTS: Among 102 patients with AGC simulating EGC, 100 patients (98%) had tumors with depressed type appearance. The frequencies of serosal invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion, and liver metastasis were significantly lower in AGC simulating EGC than in Borrmann type tumors. The prognosis of AGC simulating EGC was significantly better than that of the Borrmann type tumors. Multivariate analysis indicated that the gross appearance was an independent prognostic factor. In patients with AGC simulating EGC which invaded to the the muscularis propria (MP), most lymph node metastasis was restricted with the perigastric lymph nodes (1st-titer lymph nodes) and lymph node metastasis to 2nd-titer lymph nodes was only observed at station 8a. CONCLUSION: AGC simulating EGC is less advanced in comparison with Borrmann type advanced gastric cancer. Based on the results of susceptible sites for lymph node metastasis in the current study, limited lymph node dissection could be indicated for AGC simulating EGC whose depth of invasion is MP.

Treatment of patients with stage IV gastric cancer.

PURPOSE: Treatment of patients with stage IV gastric cancer is controversial. This study was retrospectively designed to elucidate the best treatment for these patients. METHODS: Between 2003 and 2010, a total of 558 patients with gastric cancer were treated at the Department of Surgery, Tottori University Hospital, 96 (17.2 %) of whom were diagnosed with stage IV. Among 96, 54 underwent palliative gastrectomy while 42 underwent chemotherapy, exploratory laparotomy, or gastrojejunostomy for unresectable cases. Surgical morbidity, mortality, and patient survival were analyzed with respect to several factors. RESULTS: Among resected cases, high age, R2 operation, and neoadjuvant chemotherapy did not increase the occurrence of postoperative complications. Patient age, R1 operation, and sufficient chemotherapy were indicated as better prognostic factors for resected stage IV gastric cancers. Even after R2 operation, continuous chemotherapy with changing regimens prolonged R2 resected patients' survival to 25 months (mean). In unresectable cases, bypass operation did not affect patients' survival. But, chemotherapy with changing regimens prolonged the survival of unresectable cases. CONCLUSIONS: Adequate management can resolve surgery-related morbidity, and continuous chemotherapy may be one of the most important prognostic factors in stage IV gastric cancer.

Usefulness of palliative prognostic score in the treatment of patients with non-resectable gastric cancer.

The aim of this study was to evaluate the clinical usefulness of the palliative prognostic (PaP) score in patients with non-resectable advanced gastric cancer. The PaP score was calculated prior to each course of chemotherapy in 44 consecutive patients with non-resectable advanced gastric cancer between 2003 and 2010 at the Tottori University Hospital, Yonago, Japan. The prognosis was evaluated according to the PaP score and the different chemotherapeutic agents. The median survival time (MST) was 10 months. The PaP score classified the heterogeneous patient sample into three isoprognostic groups with regard to the possibility of a 1-month survival period, with 28 patients in group A (>70% chance), 12 in group B (30-70% chance) and 4 in group C (<30% chance). The MST of the three groups was 11, 3 and 1 months for group A, B and C, respectively. In group A, chemotherapeutic regimens did not affect patient survival, although the docetaxel regimen prolonged survival of patients in group B. In conclusion, the PaP score may be useful in selecting the best chemotherapeutic regimen in patients with non-resectable gastric cancer.

Prognosis of patients with gastric cancer who underwent proximal gastrectomy.

Proximal gastrectomy (PG) has been introduced for patients who are preoperatively diagnosed with early gastric cancer located in the upper third of the stomach. In the present study, we compared the prognosis of patients who underwent PG with that of patients who underwent total gastrectomy (TG). Between 1997 and 2006, 51 patients were diagnosed with early gastric cancer located in the upper third of the stomach and underwent PG. In the same period, 35 patients were diagnosed with early gastric cancer and underwent TG. Of these, in 24 patients, the cancer was localized in the middle to upper part of the stomach, and 11 patients had multiple cancers. We compared the clinicopathologic differences and prognoses between the two groups. Significantly fewer lymph nodes were dissected in the PG group (mean, 18.2) than in the TG group (mean, 36.6;P < 0.001). Complications were detected in 17.6% of patients in the PG group and in 14.3% of patients in the TG group, which was not significant (P = 0.678). The overall and disease-specific 5-year survival rates in the 51 patients who underwent PG (88.7% and 97.1%, respectively) were not different from those in the 35 patients who underwent TG (87.6% and 93.4%; P = 0.971 and P = 0.553; respectively). These findings indicate that PG can be performed safely and may have various advantages compared with TG in terms of patients' daily lives.

Length of stay and cost for surgical site infection after abdominal and cardiac surgery in Japanese hospitals: multi-center surveillance.

PURPOSE: This study evaluated the influence of surgical site infections (SSIs) after abdominal or cardiac surgery on the post-operative duration of hospitalization and cost. METHODS: A retrospective 1:1 matched case-control study of length of stay and healthcare expenditures for patients who were discharged from nine hospitals, between April 1, 2006 and March 31, 2008, after undergoing abdominal or cardiac surgery and who did and did not have a SSI. RESULTS: Information was obtained from 246 pairs of patients who had undergone abdominal surgery and 27 pairs of patients who had undergone cardiac surgery. Overall, the mean post-operative hospitalization was 20.7 days longer and the mean post-operative healthcare expenditure was $8,791 higher in the SSI group than for the SSI-free group. Among the patients who had undergone abdominal surgery, development of SSI extended the average hospitalization by 17.6 days and increased the average healthcare expenditure by $6,624. Among the patients who had undergone cardiac surgery, SSI extended the post-operative hospitalization by an average of 48.9 days and increased the post-operative healthcare expenditure by an average of $28,534. CONCLUSIONS: Under the current healthcare system in Japan, the development of SSI after abdominal surgery necessitates extension of hospitalization two-fold and increases the post-operative healthcare expenditure 2.5-fold. Development of SSI after cardiac surgery necessitates extension of hospitalization fourfold and increases the healthcare expenditure six-fold.

Impact of surgical site infection after colorectal surgery on hospital stay and medical expenditure in Japan.

PURPOSE: To clarify the impact of surgical site infection (SSI) after colorectal surgery on the length of hospital stay and medical expenditure in Japan. METHODS: This was a multi-center, retrospective-matched case-control study. RESULTS: The total number of patients enrolled was 334 (167 case/control pairs). The average hospital stay after surgery was prolonged by 17.8 days (95% CI 11.9-23.5) and the average medical cost after surgery was increased by $5,938 (95% CI 3,610-8,367) in the SSI group versus the non-SSI group. Hospital charges comprised the largest among all cost categories and accounted for 53% of the additional cost. The hospital stay and medical costs both increased proportionately to the depth of the SSI, from 4.4 days and $608 for superficial incisional SSI, to 39.2 days and $14,448 for organ/space SSI. SSI caused by MRSA prolonged the hospital stay by 19.3 days and incurred an additional cost of $7,015. CONCLUSIONS: SSI clearly prolonged the hospital stay and increased medical costs. The numerical values revealed by this study reinforce the medical-economic importance of instigating preventive measures against SSI.

Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer.

PURPOSE: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy. METHODS: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors. CONCLUSIONS: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer.

Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.

A new pouch reconstruction method after total gastrectomy (pouch-double tract method) improved the postoperative quality of life of patients with gastric cancer.

PURPOSE: Many reconstruction methods after total gastrectomy (TG) lead patients to dumping syndrome, reflux esophagitis, and poor postoperative quality of life (QOL). To improve patients' postoperative QOL after TG, we introduce a new reconstruction method named "pouch-double tract" (PDT). METHODS: A prospective randomized study was performed between 2005 and 2007 in 29 patients who were diagnosed as stage I or II gastric cancers preoperatively. Patients were followed until the end of 2009. Conventional Roux-en-Y reconstruction (RY) was performed in 15 patients, and PDT was used in 14 patients. Postoperative patients' nutritional assessments and patients' QOL were compared between the groups. RESULTS: PDT did not increase morbidity or mortality compared with RY. Patients in the PDT group did not complain of dumping and showed better postoperative food intake. Body weight recovered better in PDT than in RY. CONCLUSION: PDT is safe and associated with better nutritional status compared with the RY.

Operative Procedure for Laparoscopy-Assisted Vagus Nerve and Pylorus-Preserving Gastrectomy (LAVNPPG) for Early Gastric Cancer.

Laparosocpy-assisted pylorus-preserving gastrectomy (LAPPG) is a widely accepted surgical procedure for the treatment of early gastric cancer in the middle third of the stomach. We have been performing this operation since 2007. Compared with traditional distal gastrectomy, LAPPG has postoperative nutritional benefits for patients. However, this procedure preserves only the pyloric branch of the vagus nerve and not the celiac branch. We found that patients retain a large amount of residual food in the gastric remnant, which interferes with the detection of secondary cancer on endoscopic follow-up. To improve the pyloric function and postoperative gastrointestinal motility, we changed our procedure during 2009 to preserve both the pyloric and celiac branches of the vagus nerve, and we named this new procedure laparoscopy-assisted vagus nerve and pylorus-preserving gastrectomy (LAVNPPG). From 2009 to 2011, 11 patients underwent LAVNPPG at our hospital. Retrospective comparison of the safety of operation, postoperative complications, and condition of the gastric remnant between LAPPG (n = 13) and LAVNPPG (n = 11) found that the occurrence of postprandial stasis and food residue in the gastric remnant tended to be lower following LAVNPPG, though the differences were not significant. These findings indicate that LAVNPPG may be an operative procedure that could replace LAPPG.

[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases].

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.