Penile cancer: Difference between revisions
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==Risk factors and prevention== |
==Risk factors and prevention== |
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===Infections=== |
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* [[ |
* [[HIV infection]]—HIV-positive men have eight-fold increased risk of developing penile cancer than HIV-negative men.<ref name="acs-risk">[http://www.cancer.org/Cancer/PenileCancer/DetailedGuide/penile-cancer-risk-factors The American Cancer Society: Penile Cancer: "What are the risk factors for penile cancer?"] [[The American Cancer Society]]</ref><ref name=Bleeker2012>{{cite doi|10.1007/978-1-84882-879-7_1}}</ref> HIV infection can be prevented by practicing [[safe sex]] or by not having sex with a person who is positive for HIV. |
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| ⚫ | * [[Human papillomavirus]]—HPV is a risk factor in the development of penile cancer.<ref name="pow-sang-2010"/> According to the [[Center for Disease Control and Prevention]] (CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States.<ref>[http://www.cancer.gov/cancertopics/types/penile/ National Cancer Institute: Penile Cancer] [[National Institutes of Health]]</ref><ref>http://www.cdc.gov/cancer/hpv/statistics/penile.htm HPV-Associated Penile Cancer Rates by Race and Ethnicity] [[Center for Disease Control and Prevention]]</ref> There are more than 120 types of HPV.<ref>{{Cite web|url = http://www.stopcancerfund.org/p-cervical-cancer-hpv/hpv-q-a/|title = HPV: Q&A|date = April 2009|website = Cancer Prevention and Treatment Fund|last = Brandel France de Bravo, Maushami DeSoto, and Krystle Seu|accessdate = August 13, 2013}}</ref> Several authors have suggested the use of [[HPV vaccine]]s such as [[Gardasil]] or [[Cervarix]] to reduce the risk of HPV and, consequently, penile cancer;<ref name=Bleeker2009/><ref name="minhas-2010"/> the use of condoms is also thought to be protective.<ref name=Bleeker2009/> |
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| ⚫ | * [[Balanitis]] |
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* [[Genital warts]]—Genital or perianal warts increase the risk of invasive penile cancer by about 3.7 times if they occurred more than two years before the reference date.<ref name="pow-sang-2010"/> About half of men with penile cancer also have [[genital warts]], which are caused by HPV.<ref name="cruk-risks"/> |
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| ⚫ | * [[Circumcision]]—Some studies show that circumcision during infancy or in childhood may provide partial protection against penile cancer, but this is not the case when performed in adulthood.<ref name="larke-2010">{{cite journal |author=Larke NL, Thomas SL, dos Santos Silva I, Weiss HA |title=Male circumcision and penile cancer: a systematic review and meta-analysis |journal=Cancer Causes Control |volume=22 |issue=8 |pages=1097–110 |year=2011 |month=August |pmid=21695385 |pmc=3139859 |
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| ⚫ | * [[Human papillomavirus]]—HPV is a risk factor in the development of penile cancer.<ref name="pow-sang-2010"/> According to the [[Center for Disease Control and Prevention]] (CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States.<ref>[http://www.cancer.gov/cancertopics/types/penile/ National Cancer Institute: Penile Cancer] [[National Institutes of Health]]</ref><ref>http://www.cdc.gov/cancer/hpv/statistics/penile.htm HPV-Associated Penile Cancer Rates by Race and Ethnicity] [[Center for Disease Control and Prevention]]</ref |
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===Hygiene and injury=== |
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* Poor [[hygiene]]—Poor hygiene can increase a man's risk of penile cancer.<ref name="minhas-2010">{{cite journal |author=Minhas S, Manseck A, Watya S, Hegarty PK |title=Penile cancer—prevention and premalignant conditions |journal=Urology |volume=76 |issue=2 Suppl 1 |pages=S24–35 |year=2010 |month=August |pmid=20691883 |doi=10.1016/j.urology.2010.04.007 |url=}}</ref><ref>{{cite journal |author=Reis AA, Paula LB, Paula AA, Saddi VA, Cruz AD |title=[Clinico-epidemiological aspects associated with penile cancer] |language=Portuguese |journal=Cien Saude Colet |volume=15 Suppl 1 |issue= |pages=1105–11 |year=2010 |month=June |pmid=20640268 |doi= |url=}}</ref> Good genital hygiene involves washing the penis, the scrotum, and the foreskin daily with water. |
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* [[ |
* Poor [[hygiene]]—Poor hygiene can increase a man's risk of penile cancer.<ref name="minhas-2010">{{cite doi |10.1016/j.urology.2010.04.007}}</ref><ref>{{cite journal |author=Reis AA, Paula LB, Paula AA, Saddi VA, Cruz AD |title=[Clinico-epidemiological aspects associated with penile cancer] |language=Portuguese |journal=Cien Saude Colet |volume=15 Suppl 1 |issue= |pages=1105–11 |year=2010 |month=June |pmid=20640268 |doi=|url=}}</ref> Good genital hygiene involves washing the penis, the scrotum, and the foreskin daily with water. |
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* [[ |
* [[Smegma]]—Smegma, a whitish substance that can accumulate beneath the foreskin, is associated with greater risk of penile cancer.<ref name="acs-risk"/><ref>{{cite journal |author=Morris BJ, Gray RH, Castellsague X, ''et al.'' |title=The Strong Protective Effect of Circumcision against Cancer of the Penis |journal=Adv Urol|volume=2011 |issue= |pages=812368 |year=2011 |pmid=21687572 |pmc=3113366 |doi=10.1155/2011/812368 |url=}}</ref> The American Cancer Society suggests that smegma may not be carcinogenic, but may increase the risk by causing irritation and inflammation of the penis.<ref name="acs-risk"/> |
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| ⚫ | * [[Balanitis]] and penile injury—Inflammation of the [[foreskin]] and/or the [[glans penis]] (balanitis) is associated with about 3.1 times increased risk of penile cancer.<ref name="pow-sang-2010"/> It is usually caused by poor hygiene, [[allergic reactions]] to certain [[soaps]], or an underlying health condition such as[[reactive arthritis]], infection, or [[diabetes]].<ref name="pubmedhealth"/> Small tears and abrasions of the penis are associated with about 3.9 times increased risk of cancer. Balanitis can be prevented by washing the penis regularly with water and by avoiding soaps with harsh ingredients. |
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| ⚫ | * [[Phimosis]]—Phimosis is a medical condition where the foreskin cannot be fully retracted over the glans. It is considered a significant risk factor in the development of penile cancer ([[odds ratio]] of 38–65).<ref name="pow-sang-2010"/> Phimosis may also be a symptom of penile cancer.<ref name="cruk-symptoms"/> Phimosis can be prevented by practising proper hygiene and by retracting the foreskin on a regular basis. |
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* [[Paraphimosis]]—Paraphimosis is a medical condition where the foreskin becomes trapped behind the glans. It is considered a risk factor for the development of penile cancer.<ref name="acs-risk"/> Paraphimosis can be prevented by not leaving the foreskin retracted for prolonged periods of time. |
* [[Paraphimosis]]—Paraphimosis is a medical condition where the foreskin becomes trapped behind the glans. It is considered a risk factor for the development of penile cancer.<ref name="acs-risk"/> Paraphimosis can be prevented by not leaving the foreskin retracted for prolonged periods of time. |
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| ⚫ | * [[Circumcision]]—Some studies show that circumcision during infancy or in childhood may provide partial protection against penile cancer, but this is not the case when performed in adulthood.<ref name="larke-2010">{{cite journal |author=Larke NL, Thomas SL, dos Santos Silva I, Weiss HA |title=Male circumcision and penile cancer: a systematic review and meta-analysis |journal=Cancer Causes Control |volume=22 |issue=8 |pages=1097–110 |year=2011 |month=August |pmid=21695385 |pmc=3139859|doi=10.1007/s10552-011-9785-9 |url=}}</ref> It has been suggested that the reduction in risk may be due to reduced risk of [[phimosis]];<ref name="acs-risk"/><ref name="larke-2010"/> other possible mechanisms include reduction in risk of [[smegma]] and [[Human papillomavirus|HPV]] infection.<ref name="acs-risk"/> Several authors have proposed circumcision as a possible strategy for penile cancer prevention;<ref name=Bleeker2009/><ref name="minhas-2010"/><ref>{{cite journal |author=de Souza KW, dos Reis PE, Gomes IP, de Carvalho EC |title=[Prevention strategies for testicular and penile cancer: an integrative review] |language=Portuguese|journal=Rev Esc Enferm USP |volume=45 |issue=1 |pages=277–82 |year=2011 |month=March |pmid=21445520 |doi= |url=}}</ref> however, the American Cancer Society points to the rarity of the disease and notes that neither the American Academy of Pediatrics nor the Canadian Academy of Pediatrics recommend routine neonatal circumcision.<ref name="acs-risk"/> |
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| ⚫ | * [[Phimosis]]—Phimosis is a medical condition where the foreskin cannot be fully retracted over the glans. It is considered a risk factor in the development of penile cancer.<ref name="pow-sang-2010"/> Phimosis may also be a symptom of penile cancer.<ref name="cruk-symptoms"/> Phimosis can be prevented by practising proper hygiene and by retracting the foreskin on a regular basis. |
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* [[Tobacco]]—Chewing or [[smoking]] tobacco increases the risk of penile cancer.<ref name="pow-sang-2010">{{cite journal |author=Pow-Sang MR, Ferreira U, Pow-Sang JM, Nardi AC, Destefano V |title=Epidemiology and natural history of penile cancer |journal=Urology |volume=76 |issue=2 Suppl 1 |pages=S2–6 |year=2010 |month=August |pmid=20691882 |doi=10.1016/j.urology.2010.03.003 |url=}}</ref> Smoking cessation has been proposed as a prevention strategy.<ref name=Bleeker2009/><ref name="minhas-2010"/> |
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===Other=== |
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* [[Lichen sclerosus]]—Lichen sclerosus is a disease causing white patches on the skin. Lichen sclerosus increases the risk of penile cancer.<ref name="minhas-2010"/><ref name=Micali2006>{{cite doi|10.1016/j.jaad.2005.05.007}}</ref> As the exact cause of lichen sclerosus is unknown, there is no known way to prevent it.<ref name="minhas-2010"/> |
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* [[Tobacco]]—Chewing or [[smoking]] tobacco increases the risk of penile cancer by 1.5–6 times depending on the duration smoking and daily number of cigarettes. Smoking cessation has been proposed as a prevention strategy.<ref name="pow-sang-2010">{{cite doi|10.1016/j.urology.2010.03.003}}</ref><ref name=Bleeker2009/><ref name="minhas-2010"/> |
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==Pathotogenesis== |
==Pathotogenesis== |
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Revision as of 19:20, 6 November 2013
| Penile cancer | |
|---|---|
| Specialty | Oncology  |
Penile cancer is a malignant growth found on the skin or in the tissues of the penis. Around 95% of penile cancers are squamous cell carcinomas. Other types of penile cancer such as Merkel cell carcinoma, small cell carcinoma, melanoma and other are generally rare.[1]
Prevalence
Penile cancer is a rare cancer in developed nations with annual incidence varying from 0.3 to 1 per 100,000 accounting for around 0.4–0.6% of all malignancies.[1] The annual incidence is approximately 1 in 100,000 men in the United States,[2] 1 in 250,000 in Australia,[3] and 0.82 per 100,000 in Denmark.[4] In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year.[5][6]
However in the developing world penile cancer is much more common. For instance, in Paraguay and Uruguay the incidence is 4.2 and 4.4 per 100,000, respectively.[1] In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men.[1]
The lifetime risk has been estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.[7]
Classification
Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types:
- basaloid (4%)
- warty (6%)
- mixed warty-basaloid (17%)
- verrucous (8%)
- papillary (7%)
- other SCC mixed (7%)
- sarcomatoid carcinomas (1%)
- not otherwise specified (49%)
Other types of carcinomas are rare and may include small cell, Merkel cell, clear cell, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as melanomas and sarcomas are even more rare.[1]
HPV positive tumors
Human papillomavirus prevalence in penile cancers is high at about 40%. HPV16 is predominate genotype accounting for approximately 63% of HPV-positive tumors. Among warty/basaloid cancers the HPV prevalence is 70–100% while in other types it is around 30%.[1]
Symptoms
- Redness of the penis[8]
- Rash on the penis[8][9]
- Foul smelling discharge from the penis[8][9]
- Pain in the penis[8]
- Growth or sore on the penis that doesn't heal within four weeks (may look like a wart, ulcer, or blister), may or may not be painful[9]
- Bleeding from the penis or from under the foreskin[9]
- Change in color of the penis[9]
- Phimosis[9]
Risk factors and prevention
Infections
- HIV infection—HIV-positive men have eight-fold increased risk of developing penile cancer than HIV-negative men.[10][11] HIV infection can be prevented by practicing safe sex or by not having sex with a person who is positive for HIV.
- Human papillomavirus—HPV is a risk factor in the development of penile cancer.[12] According to the Center for Disease Control and Prevention (CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States.[13][14] There are more than 120 types of HPV.[15] Several authors have suggested the use of HPV vaccines such as Gardasil or Cervarix to reduce the risk of HPV and, consequently, penile cancer;[1][16] the use of condoms is also thought to be protective.[1]
- Genital warts—Genital or perianal warts increase the risk of invasive penile cancer by about 3.7 times if they occurred more than two years before the reference date.[12] About half of men with penile cancer also have genital warts, which are caused by HPV.[5]
Hygiene and injury
- Poor hygiene—Poor hygiene can increase a man's risk of penile cancer.[16][17] Good genital hygiene involves washing the penis, the scrotum, and the foreskin daily with water.
- Smegma—Smegma, a whitish substance that can accumulate beneath the foreskin, is associated with greater risk of penile cancer.[10][18] The American Cancer Society suggests that smegma may not be carcinogenic, but may increase the risk by causing irritation and inflammation of the penis.[10]
- Balanitis and penile injury—Inflammation of the foreskin and/or the glans penis (balanitis) is associated with about 3.1 times increased risk of penile cancer.[12] It is usually caused by poor hygiene, allergic reactions to certain soaps, or an underlying health condition such asreactive arthritis, infection, or diabetes.[8] Small tears and abrasions of the penis are associated with about 3.9 times increased risk of cancer. Balanitis can be prevented by washing the penis regularly with water and by avoiding soaps with harsh ingredients.
- Phimosis—Phimosis is a medical condition where the foreskin cannot be fully retracted over the glans. It is considered a significant risk factor in the development of penile cancer (odds ratio of 38–65).[12] Phimosis may also be a symptom of penile cancer.[9] Phimosis can be prevented by practising proper hygiene and by retracting the foreskin on a regular basis.
- Paraphimosis—Paraphimosis is a medical condition where the foreskin becomes trapped behind the glans. It is considered a risk factor for the development of penile cancer.[10] Paraphimosis can be prevented by not leaving the foreskin retracted for prolonged periods of time.
- Circumcision—Some studies show that circumcision during infancy or in childhood may provide partial protection against penile cancer, but this is not the case when performed in adulthood.[19] It has been suggested that the reduction in risk may be due to reduced risk of phimosis;[10][19] other possible mechanisms include reduction in risk of smegma and HPV infection.[10] Several authors have proposed circumcision as a possible strategy for penile cancer prevention;[1][16][20] however, the American Cancer Society points to the rarity of the disease and notes that neither the American Academy of Pediatrics nor the Canadian Academy of Pediatrics recommend routine neonatal circumcision.[10]
Other
- Age—Penile cancer is rarely seen in men under the age of 50. About 4 out of 5 men diagnosed with penile cancer are over the age of 55.[10]
- Lichen sclerosus—Lichen sclerosus is a disease causing white patches on the skin. Lichen sclerosus increases the risk of penile cancer.[16][21] As the exact cause of lichen sclerosus is unknown, there is no known way to prevent it.[16]
- Tobacco—Chewing or smoking tobacco increases the risk of penile cancer by 1.5–6 times depending on the duration smoking and daily number of cigarettes. Smoking cessation has been proposed as a prevention strategy.[12][1][16]
- Ultraviolet light—Men with psoriasis who have been treated using UV light and a drug known as psoralen have an increased risk of penile cancer.[10][16]
Pathotogenesis
Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows:[1]
- A. Squamous hyperplasia;
- B. Low-grade penile intraepithelial neoplasia (PIN);
- C. High-grade PIN (carcinoma in situ—Bowen's disease, Erythroplasia of Queyrat and bowenoid papulosis (BP));
- D. Invasive Carcinoma of the Penis.
However in some cases non-dysplastic or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and condylomata acuminata.[1]
In HPV negative cancers the most common precursor lesion is lichen sclerosus (LS).[1]
Staging
Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.[22]
The AJCC staging guidelines are for the primary tumor as follows:[22]
- TX: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- Tis: Carcinoma in situ
- Ta: Noninvasive verrucous carcinoma
- T1: Tumor invades subepithelial connective tissue
- T2: Tumor invades the corpus spongiosum or cavernosum
- T3: Tumor invades the urethra or prostate
- T4: Tumor invades other adjacent structures
Anatomic Stage or Prognostic Groups of penile cancer are as follows:[22]
- Stage 0—Carcinoma in situ.
- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.
- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.
- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.
- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes
- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.
Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.[22]
Treatment
There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:
- Wide local excision—the tumor and some surrounding healthy tissue are removed
- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible
- Laser surgery—laser light is used to burn or cut away cancerous cells
- Circumcision—cancerous foreskin is removed
- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.
Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy. In addition to all the above, treatment of the underlying disease like brucellosis,[citation needed] is important to limit disease recurrence.
See also
- Male breast cancer
References
- ^ a b c d e f g h i j k l m Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1007/s00345-008-0302-z, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1007/s00345-008-0302-zinstead. - ^ The American Cancer Society: Penile Cancer: What is penile cancer? American Cancer Society, Last revised: January 8, 2012
- ^ [www.racp.edu.au The Official Website of the Royal Australasian College of Physicians], Published September 2010
- ^ Frisch M, Friis S, Kjær SK, Melbye M. Falling Incidence Of Penis Cancer In An Uncircumcised Population (Denmark 1943-90). BMJ: British Medical Journal. 1995;311(7018):1471.
- ^ a b Cancer Research UK: Penile Cancer: Risks and causes of penile cancer Cancer Research UK
- ^ The American Cancer Society: Penile Cancer: What are the key statistics about penile cancer American Cancer Society, Last revised: January 18, 2012
- ^ Cold CJ, Storms MR, Van Howe RS (1997). "Carcinoma in situ of the penis in a 76-year-old circumcised man". J Fam Pract. 44 (4): 407–10. PMID 9108839.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c d e PubMed Health PubMed, Last Reviewed: September 16, 2011
- ^ a b c d e f g Cancer Research UK: Penile Cancer: Symptoms of penile cancer Cancer Research UK
- ^ a b c d e f g h i The American Cancer Society: Penile Cancer: "What are the risk factors for penile cancer?" The American Cancer Society
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1007/978-1-84882-879-7_1, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1007/978-1-84882-879-7_1instead. - ^ a b c d e Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.urology.2010.03.003, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/j.urology.2010.03.003instead. - ^ National Cancer Institute: Penile Cancer National Institutes of Health
- ^ http://www.cdc.gov/cancer/hpv/statistics/penile.htm HPV-Associated Penile Cancer Rates by Race and Ethnicity] Center for Disease Control and Prevention
- ^ Brandel France de Bravo, Maushami DeSoto, and Krystle Seu (April 2009). "HPV: Q&A". Cancer Prevention and Treatment Fund. Retrieved August 13, 2013.
{{cite web}}: CS1 maint: multiple names: authors list (link) - ^ a b c d e f g Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.urology.2010.04.007, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/j.urology.2010.04.007instead. - ^ Reis AA, Paula LB, Paula AA, Saddi VA, Cruz AD (2010). "[Clinico-epidemiological aspects associated with penile cancer]". Cien Saude Colet (in Portuguese). 15 Suppl 1: 1105–11. PMID 20640268.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Morris BJ, Gray RH, Castellsague X; et al. (2011). "The Strong Protective Effect of Circumcision against Cancer of the Penis". Adv Urol. 2011: 812368. doi:10.1155/2011/812368. PMC 3113366. PMID 21687572.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Larke NL, Thomas SL, dos Santos Silva I, Weiss HA (2011). "Male circumcision and penile cancer: a systematic review and meta-analysis". Cancer Causes Control. 22 (8): 1097–110. doi:10.1007/s10552-011-9785-9. PMC 3139859. PMID 21695385.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ de Souza KW, dos Reis PE, Gomes IP, de Carvalho EC (2011). "[Prevention strategies for testicular and penile cancer: an integrative review]". Rev Esc Enferm USP (in Portuguese). 45 (1): 277–82. PMID 21445520.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.jaad.2005.05.007, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/j.jaad.2005.05.007instead. - ^ a b c d "Stage Information for Penile Cancer". National Cancer Institute. Retrieved 3 November 2013.