Fecal occult blood

From Wikipedia, the free encyclopedia
Fecal occult blood
Classification and external resources

Cards and bottle used for the Hemoccult test, a type of stool guaiac test, which is no longer considered optimal for most uses.
ICD-10 R19.5
ICD-9 792.1
DiseasesDB 30751
MedlinePlus 007008
MeSH D009780

Fecal occult blood (FOB) refers to blood in the feces that is not visibly apparent. A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces).[1] Newer tests look for globin, DNA, or other blood factors including transferrin, while conventional stool guaiac tests look for heme.

Purpose

Fecal occult blood testing (FOBT), as its name implies, aims to detect subtle blood loss in the gastrointestinal tract, anywhere from the mouth to the colon. Positive tests ("positive stool") may result from either upper gastrointestinal bleeding or lower gastrointestinal bleeding and warrant further investigation for peptic ulcers or a malignancy (such as colorectal cancer or gastric cancer). The test does not directly detect colon cancer but is often used in clinical screening for that disease, but it can also be used to look for active occult blood loss in anemia[2] or when there are gastrointestinal symptoms.[3]

Nomenclature

In 2007 the nomenclature of overt, obscure and occult bleeding was clarified.[citation needed]

The different methods of testing for "fecal occult blood" as broadly considered actually test for particular components of blood or for aberrantly expressed cellular markers from the intestinal mucosa.

Methodology

There are four methods in clinical use for testing for occult blood in feces. These look at different properties, such as antibodies, heme, globin, or porphyrins in blood, or at DNA from cellular material such as from lesions of the intestinal mucosa.

  • Fecal Immunochemical Testing (FIT), and immunochemical fecal occult blood test (iFOBT). FIT products such as the Pinnacle BioLabs FIT test utilize specific antibodies to detect globin. FIT screening is more effective in terms of health outcomes and cost compared with guaiac FOBT.[4] According to the guidelines of the American College of Gastroenterology, "Annual fecal immunochemical testing is the preferred colorectal cancer detection test."[5][6]
The FIT tests are clearly superior to traditional low sensitivity gFOBT for colorectal cancer screening. FIT testing has replaced most gFOBT tests as the colon cancer screening test of choice.[7][8] This methodology can be adapted for automated test reading and to report quantitative results, which are potential factors in design of a widescale screening strategy.[9] The number of fecal samples submitted for FIT may affect the clinical sensitivity and specificity of the methodology.[8] High sensitivity gFOBT tests such as Hemoccult SENSA remains an accepted option;[8] and may retain a role in monitoring gastrointestinal conditions such as ulcerative colitis;[10] however the FIT test is clearly preferred in recent guidelines.[11]
  • Stool guaiac test for fecal occult blood (gFOBT): – The stool guaiac test involves smearing some feces onto some absorbent paper that has been treated with a chemical. Hydrogen peroxide is then dropped onto the paper; if trace amounts of blood are present, the paper will change color in one or two seconds. This method works as the heme component in hemoglobin has a peroxidase-like effect, rapidly breaking down hydrogen peroxide. In some settings such as gastric or proximal upper intestinal bleeding the guaiac method may be more sensitive than tests detecting globin because globin is broken down in the upper intestine to a greater extent than is heme.[12] There are various commercially available gFOBT tests which have been categorized as being of low or high sensitivity, and only high sensitivity tests remain an acceptable alternative to FIT testing, which is now the best-practices recommendation in colon cancer screening. Optimal clinical performance of the stool guaiac test depends on preparatory dietary adjustment.[13]
  • Fecal porphyrin quantification: – HemoQuant, unlike gFOBT and FIT, permits precise quantification of hemoglobin, and is analytically validated with gastric juice and urine, as well as stool samples. The heme moiety of intact hemoglobin is chemically converted by oxalic acid and ferrous oxalate or ferrous sulfate to protoporphyrin, and the porphyrin content of both the original sample and of the sample after hemoglobin conversion to porphyrin is quantified by comparative fluorescence against a reference standard; the specificity for hemoglobin is increased by subtracting the fluorescence of a sample blank prepared with citric acid to correct for the potential confounding effect of existing non-specific substances.[14] Precise quantification measurement has been very useful in many clinical research applications.[15]
  • Fecal DNA test: – The PreGen-Plus[16] test extracts human DNA from the stool sample and tests it for alterations that have been associated with cancer. The test looks at 23 individual DNA alterations, including 21 specific point alterations in the APC, KRAS and p53 genes, as well as testing BAT26, a gene involved in microsatellite instability (MSI).[17][18] and a proprietary DNA Integrity Assay (DIA).[citation needed]

Additional methods of looking for occult blood are being explored, including transferrin dipstick[19] and stool cytology.[20]

A positive traditional guaiac fecal occult blood test

Test performance

Reference standards

The estimates for test performance characteristics are based on comparison with a variety of reference methods including 51-chromium studies,[citation needed] analytical recovery studies in spiked stool samples, analytical recovery after ingestion of autologous blood, rarer studies of carefully quantified blood instilled at bowel surgery [citation needed] as well as other research approaches.[citation needed] Additionally, clinical studies look at variety of additional factors.

Gastrointestinal blood loss in health

In healthy people about 0.5 to 1.5 ml of blood escapes blood vessels into the stool each day.[21][22][23] Significant amounts of blood can be lost without producing visible blood in the stool, estimated as 200 ml in the stomach,[24] 100 ml in the duodenum, and lesser amounts in the lower intestine. Tests for occult blood identify lesser blood loss.

Clinical sensitivity and specificity

Fecal Immunochemical Testing (FIT) picks up as little as 0.3 ml of blood in the stool; yet this test threshold doesn't cause undue false positives from normal upper intestinal blood leakage because it does not detect occult blood from the stomach and upper small intestine. Thus the FIT test is much more specific for bleeding from the colon or lower gastrointestinal tract than alternatives.[25] The detection rate of the test decreases if the time from sample collection to laboratory processing is delayed.[26]

Stool guaiac test for fecal occult blood (gFOBT) sensitivity varies depending on the site of bleeding. Moderately sensitive gFOBT can pick up a daily blood loss of about 10 ml (about two teaspoonfuls), and higher sensitivity gFOBT can pick up lesser amounts, requires at least 2 ml. to become positive. The sensitivity of a single stool guaiac test to pick up bleeding has been quoted at 10 to 30%, but if a standard three tests are done as recommended the sensitivity rises to 92%.[27] Reduced patient compliance with the collection of three samples hampers the usefulness of this test. Further discussion of sensitivity and specificity issues that relate particularly to the guaiac method is found in the stool guaiac test article.

Fecal porphyrin quantification by HemoQuant can be false positive due to exogenous blood and various porphyrins. HemoQuant is the most sensitive test for upper gastrointestinal bleeding and therefore may be most appropriate fecal occult blood test to use in the evaluation of iron deficiency[28] Advised to stop red meat and aspirin for three days prior to specimen collection[29] False positives can occur with myoglobin, catalase, or protohemes[15] and in certain types of porphyria.[citation needed]

The DNA based PreGen-Plus was four times more sensitive than fecal blood testing, including detection of early stage disease, when treatment is most effective.[30] Sensitivity increased to 51.6% compared to 12.9%.[31] Additional clinical trials of the PreGen-Plus method are underway to more fully characterize its clinical performance.[32] Expanding the range of DNA testing by looking at additional known genetic markers, such as CTNNB1, or by analyzing epigenetically methylated genes[33] such as MLH1 which is very common in serrated polyps with microsatellite instability (MSI)[34][35] and in proximal colon tumours that have poorer differentiation, does not appear to appreciably increase the sensitivity of the method because CTNNB1 mutations are infrequent in sporadic colorectal cancer, and because BAT26 alterations and lack of MLH1 expression show a high degree of overlap.[36]

Clinical application

The stool guaiac test for hidden (occult) blood in the stool can be done at home or in the doctor's office, or can be performed on samples submitted to a clinical laboratory. Testing kits are available at pharmacies in some countries without a prescription, or a health professional may order a testing kit for use at home. If a home fecal occult blood test detects blood in the stool it is recommended to see a health professional to arrange further testing.[37]

Sources of gastrointestinal bleeding

Gastrointestinal bleeding has many potential sources, and positive results usually result in further testing for the bleeding site, usually looking for lower gastrointestinal bleeding before upper gastrointestinal bleeding causes unless there are other clinical clues.[38] Colonoscopy is usually preferred to computerized tomographic colonography.[39]

An estimated 1–5% of large tested populations have a positive fecal occult blood test.[citation needed] Of those, about 2–10% have cancer, while 20–30% have adenomas.

A positive test can result from upper gastrointestinal bleeding or lower gastrointestinal bleeding. The common causes are:

In the event of a positive fecal occult blood test, the next step in the workup is a form of visualization of the gastrointestinal tract by one of several means:

  1. Sigmoidoscopy, an examination of the rectum and lower colon with a lighted instrument to look for abnormalities, such as polyps.
  2. Colonoscopy, a more thorough examination of the rectum and entire colon.
  3. Virtual colonoscopy
  4. Endoscopy refers to upper gastrointestinal endoscopy. It is sometimes performed with chromoendoscopy, a method that assists the endoscopist by enhancing the visual difference between cancerous and normal tissue, either by marking the abnormally increased DNA content (toluidine blue) or failing to stain the tumor, possibly due to decreased surface glycogen on tumor cells(Lugol).[40][41] Infrared fluorescent endoscopy[citation needed] and ultrasonic endoscopy[citation needed] can interrogate vascular abnormalities such as esophageal varices.
  5. Double contrast barium enema: a series of x-rays of the colon and rectum.

Stool color

Although red or black stools can be an indication of bleeding, a dark or black color can be due to black licorice, blueberries, iron supplements, lead, Pepto-bismol, and a red color can come from natural or artificial coloring such as red gelatin, popsicles, Kool-Aid, and large amounts of beets.

Colorectal cancer screening

Screening methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials. Evidence for other colon cancer screening tools such as iFOBT or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.

Guaiac FOB testing of average risk populations may reduce the mortality associated with colon cancer by about 25%.[42] It is not always cost effective to screen a large population.[43][44][45][46]

If colon cancer is suspected in an individual (such as in someone with an unexplained anemia) fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive.

The 2009 recommendations of the American College of Gastroenterology (ACG)[47] suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 years in average-risk individuals, beginning at age 50. The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred and which should be offered to patients who decline colonoscopy or another cancer prevention test. However, two other recent guidelines, from the US Multisociety Task Force (MSTF)[48] and the US Preventive Services Task Force (USPSTF)[49] while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there were no clear difference in overall performance between these methods.

In 2006, the Australian Government introduced the National Bowel Cancer Program and has been updated many times with targeted screening will be done of all Australians aged over 50 to 74 by 2017–2018. Cancer Council Australia recommended that FOBT should be done every two years. Gradually government fund disbursement made some people are not yet eligible for the national program and should pay for a FOBT by themself.[50]

In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is strongly discouraged.[51]

Iron deficiency anemia

An extensive literature has examined the clinical value of FOBT in iron deficiency anemia.

Gastrointestinal disease and medications

Conditions such as ulcerative colitis or certain types of relapsing infectious diarrhea can vary in severity over time, and FOBT may assist in assessing the severity of the disease. Medications associated with gastrointestinal bleeding such as Bortezomib are sometimes monitored by FOBT.

Alcoholism

Several aspects of FOBT in alcoholism warrant further discussion.

Outpatient clinics

Several studies have reported clinical benefit from gFOBT testing including urology and gynecology clinics.[citation needed]

Inpatient guaiac testing

Several studies have questioned the traditional Admission Screening Guaiac (ASG). [citation needed] The utility of following stool guaiac in ICU settings is also questioned. [citation needed]

Testing of upper gastrointestinal or aerodigestive tract secretions for occult blood

The use of tests for occult blood in disorders of the mouth, nasal passages, esophagus, lungs and stomach, while analogous to fecal testing, is often discouraged, due to technical considerations including poorly characterized test performance characteristics such as sensitivity, specificity, and analytical interference. However, chemical confirmation that coloration is due to blood rather than coffee, beets, medications, or food additives can be of significant clinical assistance.

A related concept to colon cancer screening by FOBT, based on most neoplasms affecting the surface epithelium and losing small amounts of blood but no visible blood loss, is screening in populations at high risk for esophageal or gastric cancers by testing for blood by swallowing a small capsule that is recovered after 3 to 5 minutes by gentle retrieval by means of an attached nylon thread.[52]

Regulatory impact

Regulations from the Joint Commission may have unintentionally decreased digital rectal examination and FOBT in hospital settings such as Emergency Departments.[53][54]

Fecal occult blood in marathon runners

Gastrointestinal (GI) complaints and low intensity GI bleeding frequently occur in marathon runners.[55] Strenuous exercise, particularly in elite athlete runners and less frequently in other exercise activities, can cause acute incapacitating gastrointestinal symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and gastrointestinal bleeding.[56] Approximately one third of endurance runners experience transient but exercise limiting symptoms, and repetitive gastrointestinal bleeding occasionally causes iron deficiency and anaemia.[57] Runners can sometimes experience significant symptoms including hematemesis.[58] Exercise is associated with extensive changes in gastrointestinal (GI) tract physiology, including diversion of blood flow from the GI tract to muscle and lungs, decreased GI absorption and small intestinal motility, increased colonic transit, neuroimmunoendocrine changes in hormones and peptides such as vasoactive intestinal peptide, secretin and peptide-histidine-methionine.[59] Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various leucocytes, and in immunoglobulin levels and major histocompatibility complex expression.[60] Symptoms can be exacerbated by dehydration or by pre-exercise ingestion of certain foods and hypertonic liquids, and lessened by adequate training.[59]

Ingestion of 800 mg of cimetidine 2 hr before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding.[61] Conversely, 800 mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and postrace guaiac test positivity but did not affect race performance.[62]

Additional studies have reviewed the effect of cimetidine and of PPI [citation needed]

Role of endoscopy in marathon runners with positive FOBT [citation needed]

This is a different process than march hemoglobinuria.[citation needed]

See also

References

  1. ↑ Occult Gastrointestinal Bleeding: Detection, Interpretation, and Evaluation. Beg M et al. JIACM 2002; 3(2): 153–58. Full text PDF accessioned 2010/10/26 http://medind.nic.in/jac/t02/i2/jact02i2p153.pdf
  2. ↑ Harewood GC, Ahlquist DA (2000). "Fecal occult blood testing for iron deficiency: a reappraisal". Dig Dis 18 (2): 75–82. doi:10.1159/000016968. PMID 11060470. 
  3. ↑ Bardhan PK, Beltinger J, Beltinger RW, Hossain A, Mahalanabis D, Gyr K (January 2000). "Screening of patients with acute infectious diarrhoea: evaluation of clinical features, faecal microscopy, and faecal occult blood testing". Scand. J. Gastroenterol. 35 (1): 54–60. doi:10.1080/003655200750024533. PMID 10672835. 
  4. ↑ Quintero, E. (2009). "¿Test químico o test inmunológico para la detección de sangre oculta en heces en el cribado del cáncer colorrectal?". Gastroenterología y Hepatología 32 (8): 565–576. doi:10.1016/j.gastrohep.2009.01.179. PMID 19577340. 
  5. ↑ Douglas, K.; Johnson, Anderson, Schoenfeld (24 Feb 2009). "American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008". Am J Gastroenterology (advance online publication). 
  6. ↑ Colorectal Cancer http://patients.gi.org/topics/colorectal-cancer
  7. ↑ Young GP, Cole SR (March 2009). "Which fecal occult blood test is best to screen for colorectal cancer?". Nat Clin Pract Gastroenterol Hepatol 6 (3): 140–41. doi:10.1038/ncpgasthep1358. PMID 19174764. 
  8. ↑ Quintero E (October 2009). "[Chemical or immunological tests for the detection of fecal occult blood in colorectal cancer screening?]". Gastroenterol Hepatol (in Spanish; Castilian) 32 (8): 565–76. doi:10.1016/j.gastrohep.2009.01.179. PMID 19577340. 
  9. ↑ Berchi C, Bouvier V, Réaud JM, Launoy G (March 2004). "Cost-effectiveness analysis of two strategies for mass screening for colorectal cancer in France". Health Econ 13 (3): 227–38. doi:10.1002/hec.819. PMID 14981648. 
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  16. ↑ PreGen-Plus™ Fact Sheet. full text accessioned 2010 November 3 at http://www.noaw.com/PDF/fs_pregen.pdf
  17. ↑ Jin YM, Li BJ, Qu B, Du YJ (August 2006). "BRAF, K-ras and BAT26 mutations in colorectal polyps and stool". World J. Gastroenterol. 12 (32): 5148–52. PMID 16937524. 
  18. ↑ Cravo M, Lage P, Albuquerque C et al. (July 1999). "BAT-26 identifies sporadic colorectal cancers with mutator phenotype: a correlative study with clinico-pathological features and mutations in mismatch repair genes". J. Pathol. 188 (3): 252–57. doi:10.1002/(SICI)1096-9896(199907)188:3<252::AID-PATH354>3.0.CO;2-3. PMID 10419591. 
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  29. ↑ Title etc http://www.mayomedicallaboratories.com/test-catalog/Overview/9220 acc on etc
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  34. ↑ Hawkins NJ, Ward RL (September 2001). "Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas". J. Natl. Cancer Inst. 93 (17): 1307–13. doi:10.1093/jnci/93.17.1307. PMID 11535705. 
  35. ↑ Hamilton SR (September 2001). "Origin of colorectal cancers in hyperplastic polyps and serrated adenomas: another truism bites the dust". J. Natl. Cancer Inst. 93 (17): 1282–83. doi:10.1093/jnci/93.17.1282. PMID 11535695. 
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  43. ↑ Mandel JS, Bond JH, Church TR et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Eng J Med 1993; 328: 1365–71.
  44. ↑ Hardcastle JD, Chamberlain JO, Robinson MHE et al. Randomised controlled trial of fecal occult blood screening for colorectal cancer. Lancet 1996; 348: 1472–77.
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  46. ↑ Kewenter J, Brevinge H, Engaras B et al. Results of screening,rescreening and follow up in a prospective randomized study for detection of colorectal cancer by fecal occult-blood testing: results of 68,308 subjects. Scand J Gastroenterol 1994; 29: 468–73.
  47. ↑ Rex DK et al. Am J Gastroenterol. 2009; 104: 739–50.
  48. ↑ Levin, B.; Lieberman, D. A.; McFarland, B.; Smith, R. A.; Brooks, D.; Andrews, K. S.; Dash, C.; Giardiello, F. M.; Glick, S.; Levin, T. R.; Pickhardt, P.; Rex, D. K.; Thorson, A.; Winawer, S. J. (2008). "Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology". CA: A Cancer Journal for Clinicians 58 (3): 130. doi:10.3322/CA.2007.0018. 
  49. ↑ USPSTF Agency for Healthcare Research and Quality. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008; 149: 627–37. Also available at Screening for colorectal cancer, topic page: http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm accessioned 2010 October 26, which has several hyperlink extensions to several extensive reviews, including accessible articles with recommendation statements, clinical background summary, decision analysis, systematic review, and evidence synthesis.
  50. ↑ "Bowel cancer screening". Retrieved July 4, 2013. 
  51. ↑ Collins JF, Lieberman DA, Durbin TE, Weiss DG (January 2005). "Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice". Ann. Intern. Med. 142 (2): 81–85. PMID 15657155. 
  52. ↑ Qin DX, Wang GQ, Zuo JH et al. (January 1993). "Screening of esophageal and gastric cancer by occult blood bead detector". Cancer 71 (1): 216–18. doi:10.1002/1097-0142(19930101)71:1<216::AID-CNCR2820710133>3.0.CO;2-#. PMID 8416718. 
  53. ↑ Adams BD, McHugh KJ, Bryson SA, Dabulewicz J (February 2008). "The law of unintended consequences: The Joint Commission regulations and the digital rectal examination". Ann Emerg Med 51 (2): 197–201, 201.e1. doi:10.1016/j.annemergmed.2007.07.022. PMID 17961818. 
  54. ↑ Cleveland NJ, Yaron M, Ginde AA (August 2010). "The effect of removal of point-of-care fecal occult blood testing on performance of digital rectal examinations in the emergency department". Ann Emerg Med 56 (2): 135–41. doi:10.1016/j.annemergmed.2009.12.021. PMID 20060198. 
  55. ↑ Halvorsen FA, Lyng J, Ritland S (May 1986). "Gastrointestinal bleeding in marathon runners". Scand. J. Gastroenterol. 21 (4): 493–97. doi:10.3109/00365528609015168. PMID 3487825. 
  56. ↑ de Oliveira EP, Burini RC (September 2009). "The impact of physical exercise on the gastrointestinal tract". Curr Opin Clin Nutr Metab Care 12 (5): 533–38. doi:10.1097/MCO.0b013e32832e6776. PMID 19535976. 
  57. ↑ Peters HP, De Vries WR, Vanberge-Henegouwen GP, Akkermans LM (March 2001). "Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract". Gut 48 (3): 435–39. doi:10.1136/gut.48.3.435. PMC 1760153. PMID 11171839. 
  58. ↑ Weaver LT. Do some marathon runners bleed into the gut? (letter response to a previous article) BMJ 1984; 288:65 full text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1444190/pdf/bmjcred00482-0081c.pdf
  59. ↑ 59.0 59.1 Brouns F, Beckers E (April 1993). "Is the gut an athletic organ? Digestion, absorption and exercise". Sports Med 15 (4): 242–57. PMID 8460288. 
  60. ↑ Venkatraman JT, Pendergast DR (2002). "Effect of dietary intake on immune function in athletes". Sports Med 32 (5): 323–37. doi:10.2165/00007256-200232050-00004. PMID 11929359. 
  61. ↑ Moses FM, Baska RS, Peura DA, Deuster PA (October 1991). "Effect of cimetidine on marathon-associated gastrointestinal symptoms and bleeding". Dig. Dis. Sci. 36 (10): 1390–4. doi:10.1007/BF01296804. PMID 1914760. 
  62. ↑ Baska RS, Moses FM, Deuster PA (August 1990). "Cimetidine reduces running-associated gastrointestinal bleeding. A prospective observation". Dig. Dis. Sci. 35 (8): 956–60. doi:10.1007/BF01537243. PMID 2384041. 

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noco/cong/tumr, sysi/epon

proc, drug (A2A/2B/3/4/5/6/7/14/16), blte

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