Validation of the Korean National Healthcare-associated Infections Surveillance System (KONIS): an intensive care unit module report.

BACKGROUND: National surveillance data should be validated to identify methodological problems within the surveillance programme and data quality issues. AIM: To test the validity of healthcare-associated infection (HAI) rate data from the Korean National Healthcare-associated Infections Surveillance System (KONIS). METHODS: Records from intensive care units of 12 (14.8%) of 81 participating hospitals for January-March 2014 were examined. The validation team reviewed 406 medical records of 110 patients with 114 reported HAIs - including 34 urinary tract infections (UTIs), 57 bloodstream infections (BSIs) and 23 cases of pneumonia (PNEU) - and 296 patients with no reported HAIs during one-day visits conducted in August and September 2014. The reviewers' diagnosis of HAI was regarded as the reference standard; in ambiguous cases, the KONIS Steering Committee confirmed the diagnosis of HAI. FINDINGS: Sensitivity values for UTIs, BSIs and PNEU were 85.3%, 74.0% and 66.7%, and specificity values were 98.7%, 99.1% and 98.7%, respectively. Positive predictive values were 85.3%, 94.7% and 78.3%, and negative predictive values were 98.7%, 94.6% and 97.7%, respectively. Sensitivity for PNEU was lower than that for UTIs and BSIs. The hospitals participating in KONIS infrequently reported conditions that were not HAIs. Sensitivity for BSIs was lower in this study than in KONIS validation studies conducted in 2008 and 2010. CONCLUSIONS: KONIS data are generally reliable; however, sensitivity for BSIs exhibited a decrease. This study shows the need for ongoing validation and continuous training of surveillance personnel to maintain the accuracy of surveillance data.

Advancing the framework for considering the effects of climate change on worker safety and health.

In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering). Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.

Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean Nosocomial Infection Surveillance System.

BACKGROUND: Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). AIM: To evaluate the Korean Nosocomial Infection Surveillance System (KONIS) in order to assess its effects on SSI since it was introduced. METHODS: SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran-Armitage test. FINDINGS: The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60-69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. CONCLUSION: The SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS.

Trends in the distribution and antimicrobial susceptibility of causative pathogens of device-associated infection in Korean intensive care units from 2006 to 2013: results from the Korean Nosocomial Infections Surveillance System (KONIS).

BACKGROUND: For all countries, information on pathogens causing healthcare-associated infections is important in order to develop proper strategies for preventing and treating nosocomial infections. AIM: To assess the change in frequencies and antimicrobial resistance of pathogens causing device-associated infections (DAIs) in intensive care units (ICUs) in South Korea between July 2006 and June 2014. METHODS: Data from the Korean Nosocomial Infections Surveillance System (KONIS) were analysed, including three major DAI types in ICUs. FINDINGS: The frequency of Gram-negative bacteria gradually increased for central line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) (from 24.6% to 32.6% and from 52.8% to 73.5%, respectively). By contrast, the frequency of Gram-positive bacteria decreased from 58.6% to 49.2% for CLABSI, and from 44.3% to 23.8% for VAP (P < 0.001). Staphylococcus aureus was the most frequent causative pathogen in CLABSI throughout the surveillance period, but for VAP was replaced as the most frequent pathogen by Acinetobacter baumannii as of 2010. Candida albicans was the most frequent pathogen for catheter-associated urinary tract infection. The meticillin resistance rate in S. aureus decreased from 95% to 90.2% (P < 0.001); amikacin resistance in Klebsiella pneumoniae and Escherichia coli decreased from 43.8% to 14.7% and from 15.0% to 1.8%, respectively (P < 0.001); imipenem resistance in A. baumannii increased from 52.9% to 89.8% (P < 0.001). CONCLUSION: The proportion of Gram-negative bacteria as nosocomial pathogens for CLABSI and VAP has increased. The prevalence of A. baumannii causing DAIs in Korean ICUs has increased rapidly, as has the rate of carbapenem resistance in these bacteria.

Trends in the incidence rate of device-associated infections in intensive care units after the establishment of the Korean Nosocomial Infections Surveillance System.

BACKGROUND: The effectiveness of continuous nationwide surveillance on healthcare-associated infections should be investigated in each country. AIM: To assess the rate of device-associated infections (DAIs) in intensive care units (ICUs) since the establishment of the Korean Nosocomial Infections Surveillance System (KONIS). METHODS: Nationwide data were obtained on the incidence rate of DAI in ICUs reported to KONIS by all participating hospitals. The three major DAIs were studied: ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CABSI), and catheter-associated urinary tract infection (CAUTI). The pooled and year-wise incidence rates (cases per 1000 device-days) of these DAIs were determined for the period 2006 and 2012. In addition, data from institutions that had participated in KONIS for at least three consecutive years were analysed separately. FINDINGS: The number of ICUs participating in KONIS gradually increased from 76 in 2006 to 162 in 2012. Between 2006 and 2012, the incidence rate per 1000 device-days for VAP decreased significantly from 3.48 to 1.64 (F = 11, P < 0.01), for CAUTI the rate decreased non-significantly from 1.85 to 1.26 (F = 2.02, P = 0.07), and for CABSI the rate also decreased non-significantly from 3.4 to 2.57 (F = 1.73, P = 0.12). In the 132 ICUs that had participated in KONIS for at least three consecutive years, the VAP rate significantly decreased from the first year to third year (F = 20.57, P < 0.01), but the rates of CAUTI (F = 1.06, P = 0.35) and CABSI (F = 1.39, P = 0.25) did not change significantly. CONCLUSION: The decreased incidence rate of VAP in ICUs in Korea might be associated with the continuous prospective surveillance provided by KONIS.

Endoscopic submucosal dissection or transanal endoscopic microsurgery for nonpolypoid rectal high grade dysplasia and submucosa-invading rectal cancer.

BACKGROUND AND STUDY AIMS: Transanal endoscopic microsurgery (TEM) has been shown to be highly effective for early rectal cancer, and endoscopic submucosal dissection (ESD) has been introduced to treat noninvasive colorectal neoplasia. The aim of this study was to compare the outcomes of ESD and TEM for superficial early rectal cancer. PATIENTS AND METHODS: We retrospectively analyzed 63 patients with nonpolypoid rectal high grade dysplasia or submucosa-invading cancer who were treated with ESD or TEM, and compared clinical outcomes and safety between the treatment groups. RESULTS: 30 patients underwent ESD and 33 underwent TEM. For ESD compared with TEM, en bloc resection rates were 96.7% vs. 100% (P = 0.476) and R0 resection rates were 96.7 % vs. 97.0 % (P = 1.000). There were no cases of local recurrence or distant metastasis in either group. Antibiotics were required in 11 patients (36.7%) in the ESD group and 33 (100%) in the TEM group (P < 0.001). There was no difference in net procedure time although ESD was associated with shorter total procedure time and hospital stay than TEM, with mean (standard deviation [SD]) 84.0 (51.2) vs. 116.4 (58.5) min (P = 0.0023), and 3.6 (1.2) vs. 6.6 (3.5) days (P < 0.001), respectively. There were no significant differences in complications between the two groups. CONCLUSIONS: Both ESD and TEM are effective and oncologically safe for treating nonpolypoid rectal high grade dysplasia and submucosa-invading cancers. ESD has the additional advantages of minimal invasiveness and avoidance of anesthesia. Therefore, ESD could be recommended as a treatment option for superficial early rectal cancers.

Outcomes after repeated resection for recurrent pulmonary metastases from colorectal cancer.

BACKGROUND: It remains controversial whether metastasectomy is still feasible in patients with pulmonary recurrence from colorectal cancer, after initial metastasectomy. The aim of this study was to evaluate outcomes of repeated metastasectomy in these patients. MATERIALS AND METHODS: From 1995 to 2007, 202 patients had received a pulmonary metastasectomy from colorectal cancer at our institution. Over a median follow-up of 28.9 months, 48 patients received second metastasectomy (29 wedge resections, 5 segmentectomies, 13 lobectomies, and 1 completion pneumonectomy). The median disease-free interval was 9.6 months. Among these 48 patients, 28 showed pulmonary recurrence again and of those, 10 patients received third metastasectomy (two wedge resections, two segmentectomies, four lobectomies, and two completion pneumonectomies). RESULTS: There was no postoperative mortality. Of the 48 patients who underwent second metastasectomy, overall and disease-free 5-year survivals were 79% and 49%, respectively, after second operation. Of the 10 patients who received third metastasectomy, overall survival was 78% at 5 years after last operation. CONCLUSIONS: Repeated resection after initial metastasectomy can be carried out safely and provides long-term survival in patients with recurrent pulmonary metastasis from colorectal cancer. Our findings indicate that close follow-up for the early detection of recurrence and parenchyma-saving resection can improve the results after repeated resection.

In vitro chemosensitivity based on depth of invasion in advanced colorectal cancer using ATP-based chemotherapy response assay (ATP-CRA).

BACKGROUND: Tumors are composed of subpopulations of cells with heterogeneous characteristics that allow for tumor progression and development of treatment resistance. The purpose of this study was to determine if there is heterogeneity in the in vitro chemosensitivity in different invasive sections of a single tumor. MATERIALS AND METHODS: Chemosensitivity in advanced colorectal cancer specimens was examined using an ATP-based chemotherapy response assay. Four chemotherapeutic agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, and mitomycin) were used for chemosensitivity studies. Tumor tissues were obtained from the superficial (mucosa/submucosa) and deep parts (muscle/subserosa/serosa), respectively. Twenty patients who had results for both the superficial and deep parts were evaluated. RESULTS: The chemosensitivity study showed variable cell death rates in both parts of the tumor. Regression analysis showed some correlations with 5-FU and irinotecan, but not with oxaliplatin or mitomycin. With the exception of three patients in whom no drug was recommended, at least one chemotherapeutic drug showed some consistency between the superficial and deep parts of the tumor. Mitomycin was the most frequently active agent for the superficial part. In the deep part, oxaliplatin and mitomycin were the most active agents. CONCLUSIONS: There may be heterogeneity in the responses to anti-chemotherapeutic agents in advanced colorectal cancer, according to the depth of invasion. Therefore, in clinical situations, chemosensitivity test specimens should be mixed with various parts of the whole tumor in order to obtain representative chemosensitivity and chemoresistance profiles.

Double primary malignancy in colorectal cancer patients--MSI is the useful marker for predicting double primary tumors.

BACKGROUND AND AIMS: The incidence of double primary malignancies (DPM) is known to be higher in colorectal cancer patients than the general population. And, the role of microsatellite instability (MSI) in DPM has been previously studied. We evaluated the clinical features and association between MSI and colorectal cancer patients with DPM. MATERIALS AND METHODS: From September 1994 to May 2004, we reviewed 2,301 colorectal cancer patients with regard to secondary primary malignancies. A subgroup analysis was performed for MSI after January 2003. RESULTS: One hundred forty-five patients (6.3%) had a DPM identified. In DPM group, 57 patients had a synchronous DPM (39.3%), and 88 patients had a metachronous malignancy (60.7%). Male gender (p<0.001) and colon cancer (p<0.001) were the factors related with the development of the DPM. Most of the second malignancies occurred within 3 years after the primary operation. The common second malignancies were stomach (58 patients, 40%) and lung (21 patients, 14.5%). In the subgroup analysis, there was a higher frequency of DPM in the MSI group when compared to the microsatellite stable group (p=0.021). CONCLUSIONS: The careful pre- and postoperative evaluation should be paid for detecting DPM as well as for detecting recurrence in colorectal cancer patients. The results of this study suggest that MSI might be a useful marker for the detection of DPM in colorectal cancer patients.

The clinical outcome and prognostic factors after multi-visceral resection for advanced colon cancer.

AIM: The value of multi-visceral resection (MVR) for treating primary advanced colon cancer infiltrating into the neighboring organs had been debated because of the high mortality. METHODS: We reviewed 1288 patients who underwent curative resection for pT3-4 colon cancer without distant metastasis from 1994 to 2004. RESULTS: Eighty four patients (6.5%) with colon cancer infiltrating into the neighboring organs (cT4) underwent MVR. The accuracy of the intra-operative decision for true invasion (pT4) was 35.7%. Major surgical morbidity occurred in 11 patients of the standard resection group (0.9%) and in 2 patients of the MVR group (2.3%) (p = 0.206). Most of the recurrence was distant metastasis (20 patients, 23.8%). Local recurrence was occurred in five patients (6.0%). The prognostic factors for recurrence and survival were pathologic tumor invasion (p = 0.033 and p = 0.016, respectively) and lymph node metastasis (p = 0.010 and p < 0.001, respectively). CONCLUSION: Multi-visceral resection was a safe and curative procedure as compared with standard resection for patients with advanced colon cancer. The cause of a poor prognosis in MVR was not local recurrence but distant metastasis. Pathologic tumor invasion and lymph node metastasis were the potential prognostic factors.

Characteristics of early colorectal carcinoma with lymph node metastatic disease.

BACKGROUND/AIMS: Endoscopic resection may safely and effectively remove early colorectal cancers. However, additional surgical treatment is needed in cases with metastatic lymph nodes for curative treatment. The purpose of this study was to investigate the correlation between lymph node metastasis and various pathological parameters in early colorectal cancers. METHODOLOGY: The clinicopathological records of 3,557 colorectal adenocarcinoma patients who underwent surgical resection at the Samsung Medical Center from August 1995 to June 2005 were reviewed. One hundred forty seven tissue samples with early colorectal cancer were used in this study. Various parameters were studied including gender, location, macroscopic appearance, differentiation, lymphatic tumor emboli, and the depth of tumor invasion. RESULTS: Twenty five patients (17.0%) had lymph node metastasis. Male gender, left colon, macroscopically depressed lesions, moderately or poorly differentiated carcinoma, depth of tumor invasion (Sm2 or Sm3), and presence of lymphatic tumor emboli were the risk factors for lymph node metastasis. CONCLUSIONS: Early colorectal cancers with male gender, location in the left colon, macroscopically depressed lesion, moderate or poor differentiation, depth in Sm2 or Sm3, and the presence of lymphatic tumor emboli have higher risk of lymph node metastasis than those without. The early colorectal cancers with these risk factors should have surgical resection.

Local recurrence after curative resection in patients with colon and rectal cancers.

BACKGROUND AND AIMS: There are a range of rates and a number of prognostic factors associated with the local recurrence of colorectal cancer after curative resection. The aim of this study was to identify the potential prognostic factors of local recurrence in patients with colon and rectal cancers. MATERIALS AND METHODS: A retrospective review of 1,838 patients who underwent curative resection of non-metastatic colorectal cancer was conducted. The patients were treated between 1994 and 2004, and had a minimum follow-up of 3 years. RESULTS: There were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9 +/- 24.5 months. With respect to colon cancer, the local recurrence rate was 6.1% (61 patients). With respect to rectal cancer, 95 patients had a local recurrence (11.3%), the rate of which was statistically greater than the local recurrence rate for colon cancer (p < 0.001). The overall recurrence rate was 16.4% (301 patients), and the local recurrence rate, with or without systemic metastases, was 8.5% (156 patients). Local recurrences occurred within 2 and 3 years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (p = 0.044 and p = 0.034, respectively), pathologic N stage (p = 0.001 and p < 0.001, respectively), and lymphovascular invasion (p = 0.013 and p = 0.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (p = 0.007) in patients with rectal cancer. CONCLUSION: Compulsive follow-up care of patients with colon and rectal cancers is needed for 3 years after curative resection, especially in patients who have adverse risk factors for local recurrence.

Decision for salvage treatment after transanal endoscopic microsurgery.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has emerged as an alternative to classic radical operation for early rectal cancer. Early rectal cancer can be treated by adequate local excision such as TEM. If there are adverse risk factors, especially poor cellular differentiation, close resection margin, or positive lymphovascular invasion or incomplete excision, a radical resection is indicated. This study aimed to clarify the factors related to recurrence for patients required to undergo a salvage operation after TEM. METHODS: This retrospective study analyzed 167 patients who underwent TEM for rectal cancer between 1994 and 2004. Of these patients, 36 with poor differentiation, mucinous carcinoma, proper muscle invasion, lymphovascular invasion, and positive resection margin were included in the analysis. RESULTS: Of the 36 patients, 12 underwent a salvage operation, and the remaining 24 did not because of poor physical condition or refusal of radical surgery. There were a total of 6 (16.7%) recurrences. One (8.3%) of the 12 patients who underwent salvage surgery had systemic recurrence. Five (20.8%) of the 24 patients who did not receive surgery had recurrence (3 local recurrences, 2 distant recurrences). Analysis of the subgroups showed that 2 (28.6%) of 7 patients with lymphovascular invasion had recurrence, and that 1 patient (100%) had a T3 lesion. Three (17.6%) of 17 patients had T2 lesions. CONCLUSIONS: For high-risk patients, TEM followed by radical surgery is the most beneficial in preventing local recurrence. Radical salvage surgery is strongly recommended if pathologic results after TEM show T3 lesion or lymphovascular invasion.

Biotransformation of phenanthrene and 1-methoxynaphthalene with Streptomyces lividans cells expressing a marine bacterial phenanthrene dioxygenase gene cluster.

The phdABCD gene cluster in a marine bacterium Nocardioides sp. strain KP7 codes for the multicomponent enzyme phenanthrene dioxygenase. phdA encoding an iron-sulfur protein large subunit alpha, phdB encoding its small subunit beta, phdC encoding ferredoxin, and phdD encoding ferredoxin reductase, were replaced in such a way that the termination codons of the preceding open reading frames were overlapped with the initiation codons of the following genes. This manipulated phdABCD gene cluster was positioned downstream of the thiostrepton-inducible promoter PtipA in a high-copy-number vector pIJ6021, and introduced into the gram-positive, soil-inhabiting, filamentous bacterium Streptomyces lividans. The recombinant S. lividans cells converted phenanthrene into a cis-diol form, which was determined to be cis-3,4-dihydroxy-3,4-dihydrophenanthrene by its UV spectral data as well as HPLC property, using the authentic sample for comparison. This biotransformation proceeded very efficiently; 200 microM and 2 mm of phenanthrene were almost completely converted to its cis-diol form in 6 h and 32 h, respectively. In addition, the S. lividans cells carrying the phdABCD gene cluster were found to transform 1-methoxynaphthalene to two products, which were identified to be 8-methoxy-2-naphthol in addition to 8-methoxy-1,2-dihydro-1,2-naphthalenediol by their EI-MS, 1H- and 13C-NMR spectral data.

Oxygenation reactions of various tricyclic fused aromatic compounds using Escherichia coli and Streptomyces lividans transformants carrying several arene dioxygenase genes.

Bioconversion (biotransformation) experiments on arenes (aromatic compounds), including various tricyclic fused aromatic compounds such as fluorene, dibenzofuran, dibenzothiophene, carbazole, acridene, and phenanthridine, were done using the cells of Escherichia coli transformants expressing several arene dioxygenase genes. E. coli carrying the phenanthrene dioxygenase (phdABCD) genes derived from the marine bacterium Nocardioides sp. strain KP7 converted all of these tricyclic aromatic compounds, while E. coli carrying the Pseudomonas putida F1 toluene dioxygenase (todC1C2BA) genes or the P. pseudoalcaligenes KF707 biphenyl dioxygenase (bphA1A2A3A4) genes was not able to convert these substrates. Surprisingly, E. coli carrying hybrid dioxygenase (todC1::bphA2A3A4) genes with a subunit substitution between the toluene and biphenyl dioxygenases was able to convert fluorene, dibenzofuran, and dibenzothiophene. The cells of a Streptomyces lividans transformant carrying the phenanthrene dioxygenase genes were also evaluated for bioconversion of various tricyclic fused aromatic compounds. The ability of this actinomycete in their conversion was similar to that of E. coli carrying the corresponding genes. Products converted from the aromatic compounds with these recombinant bacterial cells were purified by column chromatography on silica gel, and identified by their MS and 1H and 13C NMR analyses. Several products, e.g., 4-hydroxyfluorene converted from fluorene, and cis-1,2-dihydroxy-1,2-dihydrophenanthridine, cis-9,10-dihydroxy-9,10-dihydrophenanthridine, and 10-hydroxyphenanthridine, which were converted from phenanthridine, were novel compounds.

Malignant colorectal obstruction: treatment with a flexible covered stent.

PURPOSE: To evaluate the usefulness of flexible covered stents for treatment of acute colorectal obstruction secondary to malignant colorectal carcinoma. MATERIALS AND METHODS: Twenty patients with acute colorectal obstruction secondary to malignant colorectal carcinoma were treated by means of intubation of a flexible stent with fluoroscopic guidance with occasional endoscopic assistance. Two types of stents were placed (type 1, completely covered, type 2, two-thirds of proximal part uncovered). Of 15 patients with primary colorectal carcinoma, 12 underwent placement of a stent for presurgical decompression of colorectal obstruction; three, for palliative decompression. In three patients with rectosigmoid seeding from advanced gastric carcinoma and two patients with recurrent colonic carcinoma, stents were placed for palliative decompression. RESULTS: Stent placement was successful in 18 (90%) of 20 patients. Symptoms of obstruction resolved within 24 hours in 15 (75%) patients. Eight patients underwent elective single-stage surgery without complications 5-7 days after stent placement. Two patients underwent tumor resection and colostomy. In eight patients, stents provided palliative decompression of the colon. Type 1 stents migrated in four (50%) of eight patients; type 2 stents were used thereafter. CONCLUSION: Flexible stents effectively relieved acute colonic obstruction secondary to malignant rectosigmoid neoplasm. Stent placement allowed patients to undergo single-stage surgery in most cases and provided palliative decompression in cases of inoperable or disseminated disease.

Bestatin analogue from Streptomyces neyagawaensis SL-387.

A bestatin analogue, (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-valine (AHPA-Val), from the culture filtrate of Streptomyces neyagawaensis SL-387 was obtained in a chemically defined medium containing DL-3-amino-3-phenylpropionic acid. AHPA-Val was 6 times (IC50 = 1.2 micrograms/ml) as strong as bestatin (IC50 = 7.0 micrograms/ml) against porcine kidney microsomal aminopeptidase N, and 4 times (5.6 micrograms/ml) as strong as bestatin (IC50 = 20.7 micrograms/ml) against aminopeptidase N of human metastatic fibrosarcoma HT1080. To the best of our knowledge, this is the first report on the microbial production of AHPA-Val.