Table 4. The relationship of different age groups of CRC with patients’ gender.

Table 3. The relationship of anatomic location of CRC with different age groups.

Figure 3. The distribution of CRC in the R and L-sided colon among different age groups. There was significant higher percentage of CRC occurred in the L-sided colon when patients were less than 60-69 years old. However, when patients were over 69 years old, more CRC occurred in R-sided colon. Figure 4. The distribution of CRC in different age groups and gender. When patients were less than 70-79 years old, more male than female patients with CRC, however, when patients over 79 years old, more female with CRC. Male patients had about 10 years earlier to reach their peak prevalence at 60-69 years old than female patients.

Table 2. CRC, TA, SSA/P and TSA at different anatomic location of the colon.

*3 CRC and 69 TA in NOS were not included in the right or left-sided colon.

Table 1. Patients’ demography in different study groups.

*Mean age of CRC group was significantly higher than TA group (p < 0.001), SSA/P group (p < 0.001), and TSA group (p = 0.04).

Figure 2. Anatomic sub-sites of CRC and its precursors. Graph showed the distribution of CRC, TA, SSA/P, and TSA at different anatomic sub-sites in the whole colon.

Figure 1. The distribution of CRC, TA, SSA/P and TSA in the R and L-sided colon. CRC and TSA both showed predominant left-sided distribution patterns. In contrast, SSA/P showed a significant right-sided distribution pattern and TA showed a slightly prominent toward right-sided colon.

Figure 2. MB = methylene blue group, FC = fat clearance group, Co = control group; A) Mean LN numbers of the different groups. Error bars indicate 1 standard deviation. B) Rate of sufficient LN harvest (¡Ý 12 LNs) dependent on the group.

Figure 1. Technique of methylene blue injection. A) Rectal specimen and instruments needed for methylene blue injection. B) Identification of the vascular pedicel and cutting off the clip. C) Short longitudinal opening of the vessel facilitates cannulation. D) Cannulation of the artery using a standard i.v.-catheter without mandarin (multiple usage is possible). E) and F) The serosal and the mucosal layer turn into blue immediately after the injection of the first milliliters of the methylene solution.

Table 1. Clinicopathological characteristics.

Table 2. A comparison of the incidence figures for vulvar and vaginal cancers for different time periods.

Table 1. The distribution of the various histological types of vulvar and vaginal cancers in this study. * The FIGO and the American Joint Committee on Cancer (AJCC) staging systems for vaginal tumors do not include superficially invasive (Stage 1A) SCC.

Clement A. Okolo, MBBS, FMCPath; M. Olatokunboh Odubanjo, MBBS, FMCPath;*

Olutosin A. Awolude, MBBS, FMCOG; Effiong EU Akang, MBBS, FMCPath, FWACP

The objectives of this study are to give an update  on the previous studies on vulvar and vaginal cancers from the University College Hospital  (UCH), Ibadan, Nigeria, to elucidate any changes in pattern, and to enumerate some of the  factors affecting the management of these cancers at the UCH today. All the cases of cancer  of the vulva and vagina seen at the UCH between January 1981 and December 2008 were reviewed  and re-classified according to the World Health Organization (WHO) histological classification  of 2004. The results are as follows: Vaginal and vulvar cancers were the 4th (1. 4%) and 5th (1.2%) most common of the 5913 gynecological cancers seen. The mean age was 49. 7 years. Squamous cell carcinoma (SCC) was the most common histological type. Notably,  vulvar cancer is more common than vaginal cancer in the US and the UK and this opposes our  findings. We studied time periods before and after the year 2000, and found vaginal cancer  to be more common before and vulvar cancer after the year 2000. We suggest that this may be  related to the introduction of the FIGO guidelines in 2000. We conclude that it is important  to strictly adhere to the FIGO guidelines in determining the primary site of origin of these cancers in  patients with advanced local disease as this distinction has implications for clinical management. 

Key Words: vulvar, vaginal,  cancer, squamous cell carcinoma, Ibadan, Nigeria 

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Clement A. Okolo, MBBS, FMCPath;¹ M. Olatokunboh Odubanjo, MBBS, FMCPath;¹* Olutosin A. Awolude, MBBS, FMCOG;² Effiong EU Akang, MBBS, FMCPath, FWACP¹

¹ Department of Pathology, University College Hospital, Ibadan, Nigeria
² Department of Obstetrics and Gynecology, University College Hospital, Ibadan, Nigeria 

*Corresponding Author: Dept  of Pathology, University College Hospital, Ibadan, Nigeria.
(Email: todubanjo2002@yahoo.com) 

CONFLICT OF INTEREST 

None of the authors has any conflict of interest  to declare. 

[N A J Med Sci. 2013;6(2):76-81. DOI: 10.7156/najms.2013.0602076] PDF File

Clement A. Okolo, MBBS, FMCPath; M. Olatokunboh Odubanjo, MBBS, FMCPath;*

Olutosin A. Awolude, MBBS, FMCOG; Effiong EU Akang, MBBS, FMCPath, FWACP

The objectives of this study are to give an update  on the previous studies on vulvar and vaginal cancers from the University College Hospital  (UCH), Ibadan, Nigeria, to elucidate any changes in pattern, and to enumerate some of the  factors affecting the management of these cancers at the UCH today. All the cases of cancer  of the vulva and vagina seen at the UCH between January 1981 and December 2008 were reviewed  and re-classified according to the World Health Organization (WHO) histological classification  of 2004. The results are as follows: Vaginal and vulvar cancers were the 4th (1. 4%) and 5th (1.2%) most common of the 5913 gynecological cancers seen. The mean age was 49. 7 years. Squamous cell carcinoma (SCC) was the most common histological type. Notably,  vulvar cancer is more common than vaginal cancer in the US and the UK and this opposes our  findings. We studied time periods before and after the year 2000, and found vaginal cancer  to be more common before and vulvar cancer after the year 2000. We suggest that this may be  related to the introduction of the FIGO guidelines in 2000. We conclude that it is important  to strictly adhere to the FIGO guidelines in determining the primary site of origin of these cancers in  patients with advanced local disease as this distinction has implications for clinical management. 

Key Words: vulvar, vaginal,  cancer, squamous cell carcinoma, Ibadan, Nigeria 

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INTRODUCTION 

This study aims to describe the histopathological  pattern of vulvar and vaginal cancers at the University College Hospital (UCH), Ibadan.  The last study of vulvar and vaginal cancers carried out at the UCH was published in 1998.¹ This present study seeks to give an update, to elucidate any changes in pattern,  and to enumerate some of the factors affecting the management of these cancers at the UCH  today. 

Persistent Human papillomavirus (HPV) infection  is a notable risk factor for both vulvar and vaginal cancers. In the United States,  it has been reported that 40% of vulvar² and vaginal cancers³ could be attributed to Human Papillomavirus (HPV), and HPV type 16 (HPV-16) was detected  in 50-64% of high-grade vaginal intraepithelial lesions (VAIN).²

Worldwide, vulvar and vaginal cancers are rare.^4,5 Independent reports from Nigeria, United Kingdom and the United States show these cancers  to be rare.^6,7,8 In the United States, vulvar cancer accounts for 0.6% of all cancers in women,³ and vaginal cancer for 0.3% of all invasive cancers among women.² Majority of these cancers occur in developing countries.⁶ It is reported that 60% of vulvar cancers and 68% of vaginal cancers occur in developing  countries.⁶

Thomas et al⁹ described the prevalence of HPV infection in Nigerian women as well as the distribution  of various HPV subtypes among women with normal and abnormal findings on cytology or Visual  inspection with acetic acid. HPV 16 and 35 were the most common high-risk HPV types,  and HPV 42 was the most common low risk type.⁹ There is need for further epidemiological studies on the role of HPV in various cancers  in our environment, as well as the distribution of the various subtypes in these cancers. 

Worldwide and in the US, there has been profound  excitement and concern surrounding the HPV vaccine. The excitement derives from the potential  of the vaccine to reduce the burden of anogenital cancers in countries that have no screening  infrastructure. There are concerns however, that if vaccine uptake is lower in those groups  at highest risk of developing cervical cancer, current racial/ethnic or geographic disparities  could increase.⁶ For Nigerians, the HPV vaccine may be useful in reducing the burden of disease provided  we can afford them and the same HPV subtypes (mostly HPV 16 and 18) targeted by these vaccines  are important causes of cancer in Nigeria. 

METHODS 

Details of all histologically confirmed cases  of cancer of the vulva and vagina seen at the University College Hospital (UCH),  Ibadan between January 1981 and December 2008 were obtained from the records of the Ibadan  Cancer Registry. All the cases were re-classified according to the WHO histological classification  of the tumors of the vagina and the classification of the tumors of the vulva published in  2004.^4,5 The data obtained was analyzed using SPSS version 15.0. 

RESULTS 

A total of 162 cases of vulvar and vaginal cancers  were found in the records of the Ibadan Cancer Registry for the period from January 1981 to  December 2008. Seventy-eight (78) cases were from the vulva and 84 from the vagina.  Archival tissue blocks and or histopathological slides were missing for 10 of the cases and  histologic classification could not be done. A total of 5913 gynecological cancers were seen  within the study period. Vulvar cancers constituted 1.2% of all the gynecological cancers  while vaginal cancers constituted 1.4%. 

There were 4760 cancers of the cervix constituting  80.5% of the cases, 610 cancers of the ovary (10.3%), 381 cancers of the uterus (6. 4%), 84 cancers of the vagina (1.4%) and 78 cancers of the vulva (1. 3%). Cancers of the vagina  and the vulva are found to be the least common, being the 4th and the 5th most common. 

The mean age of occurrence of vulvar and vaginal  cancers was 49.7 years (±18.5 years). The 95% confidence interval was 46.8 to 52. 6 years. Peak incidence was in the 5th decade, age range was 1 to 99 years. 

One hundred and fifty-two (152) cases were classified  into various histologic types according to the WHO classifications of 2004 for vulvar and  for vaginal tumors and the frequencies of the various types is as shown in Table 1. 

The frequencies of vulvar and vaginal cancers  within different time periods (viz. 1976-1995 by Babarinsa et al, the entire period of this  study (1981-2008) and the periods in this study before and after the year 2000) are shown  in Table 2. 

A comparison of the mean of vulvar cancers seen  before the year 2000 (1981-2000) with the mean after the year 2000 (2001-2008) using the t  test was found to be statistically significant with a p value of p = 0.00021, a similar value  for vaginal cancers was p = 0.013 and for the comparison of the means of the total numbers  of vulvar and vaginal cancers before and after 2000 (p < 0.0001). 

There was a 259% increase in the average number  of vulvar cancers diagnosed per year from the period in this study before the year 2000 to  the period afterwards while the average number of vaginal cancers per year decreased by 79%. 

Click icon to read this table ———————————– Table 1. The distribution of the various histological types of vulvar and vaginal cancers in this study. * The FIGO and the American Joint Committee on Cancer (AJCC) staging systems for vaginal tumors do not include superficially invasive (Stage 1A) SCC. ———————————–

Click icon to read this table ———————————– Table 2. A comparison of the incidence figures for vulvar and vaginal cancers for different time periods. ———————————–

A comparison of the proportion of vulvar and  vaginal cancers accounted for by vulvar cancers in the period before the year 2000 with the  proportion accounted for by vulvar cancers after the year 2000 showed no statistically significant  difference at p < 0.05. Similar t test analysis for the proportions of vaginal cancers before  and after the year 2000 was also not statistically significant at p<0.05. 

DISCUSSION 

There were 5913 gynecological cancers seen over  the 28-year period of this study. This may be compared with 2330 cancers seen over the 20-year  period of the most recent previous study from the UCH, the study by Babarinsa et al.¹ These figures translate to an average of 211.2 and 116.5 gynecological cancers per year  respectively and suggest an increase in the overall incidence of gynecological cancers.¹ In addition, a comparison of the means of vulvar and vaginal cancers before the year 2000  with the means of cancers from the same site after the year 2000 show statistically significant  increases in the incidence of vulvar and vaginal cancers from the period of the first 20 years  of this study to the last 8 years. The increase in the incidence of these cancers in our environment  is likely due to increased health awareness among the population with the increasing use of  hospital services. 

An increase in the incidence of vulvar cancers  in the United States, starting from the mid-1990s has been described by the National Cancer  Institute (NCI) report for 2009.¹⁰ There were no similar figures for vaginal cancers from the NCI; however reports from the  United Kingdom¹¹ show that cancer of the vagina has remained stable over the past 25 years. It has been shown  that the incidence of pre-invasive disease of the vulva has almost doubled over the past decade,  and this may translate into a marked increase in the incidence of invasive vulvar carcinoma  in the future.¹²

In our study, cancer of the cervix was the most  common followed by cancers of the ovary, the uterus, the vagina and the vulva. In Nigeria,  cancer of the cervix had previously been shown to be the most common gynecological cancer  with cancers of the vulva and the vagina being the least common.⁶ In the United States, cancer of the uterine corpus is the most common followed by cancer  of the ovary, the cervix and then the vulva and the vagina.¹³ In the United Kingdom, ovarian cancer is most common while vulvar and vaginal cancers are  the least common. 

The relative frequencies for cancers of the vulva  and the vagina among gynecological cancers were found to be 1.3% and 1.4% in this study.  Corresponding figures from the study by Babarinsa et al¹ were 1.2% and 2% respectively. This suggests that even though the incidence of cancers of  the vulva and vagina has increased, their relative frequencies among gynecological cancers  have remained virtually stable with the incidence of the other gynecological cancers increasing  at comparable rates. 

In the United Kingdom, both cancers of the vulva  and the vagina together account for 7% of gynecological cancers diagnosed in women.^8,11In the United States, vulvar and vaginal cancers represent only 4-5%³ and 2%¹⁴ respectively of gynecological cancers. Worldwide rates for vulvar cancer range from less  than 0.3 per 100,000 females in parts of Asia to about 1.6 per 100,000 females in North America  and Europe. Rates for most parts of Africa fall about midway between the ones for Asia and  North America.⁸ This variation is probably related to differing prevalence of HPV infection in world regions,  and other lifestyle factors, especially smoking, and their interaction with HPV.⁸

In this study overall, cancers of the vagina  are more common than those of the vulva, this corroborates the findings in the studies by  Babarinsa et al,¹ Kyari et al,¹⁵ and Mohammed A et al¹⁶ but opposes the findings from the study by Nwosu SO et al,¹⁷ the United States of America¹³and the United Kingdom^8,11 When the cases diagnosed after the year 2000 were analyzed separately however,  vulvar cancer had become more common. 

When patients present late, as is often the case  with these cancers in our environment, tumor is more likely to be seen involving multiple  contiguous sites and this may lead to confusion in the determination of the primary site.  The International Federation of Gynaecology and Obstetrics (FIGO) guidelines¹⁸state that patients with tumor involvement of the vagina along with the external cervical  os proximally or the vulva distally should be classified as primary cervical or vulvar cancers  respectively. Before a diagnosis of primary vaginal carcinoma can be established,  a 5-10 year disease-free interval is required to rule out recurrent disease in those patients  with a prior pre-invasive or invasive cervical or vulvar neoplasm. The FIGO guidelines¹⁸must be followed strictly in determining the primary site of origin. Failure to do this may  result in an artificial switch whereby vaginal cancer may become more common than vulvar cancer  even if this is not the true situation. It is known that while secondary tumors of the vulva  are rare,⁵80-90% of vaginal cancers are metastatic.¹⁴

The increased detection of vulvar cancers and  the change in the relative distribution of vulvar and vaginal cancers seen after the year  2000, with vulvar cancers becoming more common than vaginal cancers, are likely due,  at least in part, to the application of the FIGO guidelines in the determination of the primary  site of origin of the gynecological cancers seen at the UCH. However, a comparison of the  proportion of the total numbers of vulvar and vaginal cancers accounted for by vulvar or vaginal  cancers in the period before the year 2000 with the proportion accounted for by cancers from  the same primary site after the year 2000 showed no statistically significant difference at  p < 0.05. This is probably due to the wide disparity observed in the percentage increase in  the average number of vulvar cancers and the percentage decrease in the average number of  vaginal cancers (259% versus 79%). A significant difference would have been most likely to  be observed if the increase in the incidence of vulvar cancers had been associated with a  comparable decrease in the incidence of vaginal cancers. 

If the changes in the incidence of vulvar and  vaginal cancers seen had been due to the use of the FIGO guidelines alone, each case of cervical  or vulvar cancer accurately diagnosed by new criteria would have resulted in one less case  of vaginal cancer, and a comparable decrease in the incidence of vaginal cancers.  In this study, the changes resulting from the strict use of the FIGO guidelines have evidently  been masked by a significant further increase in the incidence of vulvar cancers which contributes  to a higher percentage increase than that from the use of the guidelines alone, and also an  increase in the incidence of vaginal cancers contributing to a lower percentage decrease than  is expected. 

Making a distinction among vaginal, vulvar and  cervical cancers is also of importance in that the primary site of gynecological cancer significantly  impacts the choice of therapy. Standard primary treatment for vulvar cancer is surgery,  with radiation usually being added to surgery in patients with stage III or IV disease.¹⁹

The proximity of the vagina to the bladder or  rectum limits surgical treatment options for vaginal cancers and increases short- and long-term  surgical complications and functional deficits involving these organs hence the choice of  therapy is dependent on the following factors: the stage and the size of the lesion,  proximity to radiosensitive organs or organs that preclude radical resection without unacceptable  functional deficits (e.g., bladder, rectum, urethra), ability to retain a functional vagina,  the presence or absence of the uterus, and whether there has been prior pelvic radiation  therapy.²⁰

Data from randomized trials are lacking for vaginal  cancers and the choice of therapy is largely based on institutional experience with small  case series.²⁰For patients with carcinoma of the vagina in its early stages, radiation or surgery or a  combination of these treatments are standard treatment.²⁰Bulky tumors and late stage disease are often treated with chemotherapy by an extrapolation  from treatment approaches used in cervical cancer, based on shared etiologic and risk factors.  For cervical cancers, on the other hand, several randomized phase III trials have shown an  overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy  for early stage and for advanced cancers.²¹

This study spans a period of 28 years including  a significant part of the period when the relevant FIGO guidelines were not as widely used  as they are today. The FIGO Staging Classifications and Clinical Practice Guidelines for Gynecological  Cancers were published in 2000, and have been revised for the first time in March 2010.  These 28 years also overlap with some years in the study by Babarinsa et al.¹ It is likely that some of the cases from the earlier years might have been diagnosed as  vaginal cancer because the patient presented late with tumor involving multiple contiguous  sites and the vagina was more significantly involved than the cervix or the vulva. 

As mentioned earlier, the study by Babarinsa  et al¹ showed that most of our patients present late and tend to default during treatment.  Wu et al² studied vaginal cancers among different races in the United States and showed that black,  Asian Pacific Island, and Hispanic women as well as older women were more likely to be diagnosed  with late-stage disease, and these groups had lower 5-year relative survival rates than their  white, non-Hispanic, and younger counterparts. 

With early detection, vulvar cancer is highly  curable. When lymph nodes are not involved, the five-year survival rate is slightly higher  than 90 percent.¹⁰ Even in developed nations, the management of vulvar carcinoma is hampered by the fact that  diagnosis is delayed in most cases and by the choice of the proper surgical procedure.¹² The greatest difficulty in surgical management is with primary wound closure and healing,  and wound breakdown and sepsis occur commonly.²²

The mean age in this study was 49.7 years with  peak occurrence in the 5th decade. Other previous studies from Nigeria show that most patients  with vulvar and vaginal cancers are older than 50 years.^1,15,16,17In the United States of America, both cancers are also most commonly seen in persons older  than 50 years.^2,3

SCC constitutes 73.61% of vulvar cancers and  61.25% of vaginal cancers seen in this study. Squamous cell carcinoma has previously been  reported to be the most common malignant tumor of the vulva and vagina by a previous study  from Nigeria¹ and several reports from the developed nations^3,8,11 sometimes constituting as many as 95% of the cases seen. Other less common carcinomas seen  include basal cell carcinoma and adenocarcinoma. Non-epithelial malignant tumors of the vulva  include sarcomas, melanomas, Merkel cell carcinoma, yolk sac tumor, lymphomas and leukaemias.  In the vagina, the most important non-epithelial tumors are malignant melanoma and sarcoma  botryoides.⁴

Apart from keratinizing and non-keratinizing  SCC, two other specific subtypes of SCC are seen in this study: verrucous carcinoma and superficially  invasive SCC. Three (3) cases of verrucous carcinoma were found in this study. Two of the  cases were found in the vulva in patients aged 45 and 74 years. The one case found in the  vagina was in a 70 year old patient. Verrucous carcinoma (VC) of the vulva is a rare variant  of squamous cell carcinoma (SCC) of the vulva that afflicts older women, usually older than  70 years, and is characterized by a well-differentiated morphology with minimal nuclear atypia.²³Three cases of superficially invasive SCC (SISCC, previously known as microinvasive carcinoma)  were found in the vulva constituting 4.17% of all the vulvar cancers seen in this study.  Superficially invasive SCC is FIGO Stage 1A carcinoma; it is defined as a single lesion measuring  2 cm or less in diameter and with a depth of invasion of 1 mm or less. SISCC has been shown  to have a minimal risk of lymph node metastasis and it is associated with excellent prognosis.²⁴

In this study, 5 cases of adenocarcinoma were  seen in the vulva, constituting 6.94% of vulvar cancers and 15 cases in the vagina constituting  18.75% of the vaginal cancers seen in this study. The specific subtypes seen in this study  include mucinous and clear cell adenocarcinomas. Adenocarcinomas of the vulva may arise in  the Bartholin’s glands, endometriosis or ectopic cloacal tissue.⁵

Clear cell adenocarcinomas of the vagina (and  the cervix) are associated with in utero exposure to diethylstilbestrol (DES). The peak incidence  of DES- associated adenocarcinoma of the vagina is at young ages (less than 30 years) while  adenocarcinomas that are not associated with DES exposure occur primarily during postmenopausal  years.⁵

The association between the clear cell carcinomas  and in utero exposure to DES was first reported in 1971. The incidence of this disease,  which is highest for those exposed during the first trimester, peaked in the mid-1970s,  reflecting the use of DES in the 1950s.²⁰It is now extremely rare.²⁰Non朌ES-associated adenocarcinomas generally have a worse prognosis than SCC tumors,  but DES-associated clear cell tumors have a relatively good prognosis.²⁰

In this study, one case of small cell carcinoma  is found in the vagina, constituting 1.25% of vaginal cancers. Small cell carcinoma is a carcinoma  of neuroendocrine differentiation.⁴ In the vulva, it tends to occur in the Bartholin抯 gland.⁵

Ten (10) cases (13.9%) of undifferentiated carcinoma  are seen in the vulva in this study and 7 cases (8.75%) in the vagina. This is a carcinoma  lacking evidence of glandular, squamous, neuroendocrine or other types of differentiation.^4,5

Four (4, 5.56%) sarcomas are seen in the vulva  and 7 (8.75%) in the vagina. Worldwide, primary sarcomas of the vulva constitute between 1  and 2% of all vulvar and vaginal malignancies.^4,5In this study, embryonal rhabdomyosarcoma (sarcoma botyroides) is the most common sarcoma  seen in both the vulva and the vagina; all but one of all the cases of vulvar and vaginal  cancers found in persons younger than 10 years of age were diagnosed as such. Embryonal rhabdomyosarcoma  is a malignant neoplasm exhibiting striated muscle differentiation that occurs almost exclusively  in children younger than 10 years of age. 

Even though the specific etiology of most vulvar  epithelial tumors is unknown, Human papillomavirus and cigarette smoking are known to be risk  factors.⁵

In 2002, Olayemi et al reported a case of vulvar  carcinoma in pregnancy from this hospital²⁵ which showed tumor arising in condyloma acuminata, and corroborates the important role played  by HPV in vulvar cancer disease. 

Vulvar SCC has been shown to be a multifactorial  disease following two separate and independent pathways, an HPV-dependent pathway with classic  VIN as precursor lesions and an HPV-independent pathway associated with differentiated VIN  and/or lichen sclerosus.²⁶ HPV-positive carcinomas account for one-quarter to one-third of cases, occur in women on  average 20 years younger than in HPV-negative, and are associated with multiple lower genital  tract neoplasia.²⁷

Classic VIN is predominantly of the warty and  basaloid types and these types of squamous intraepithelial lesions, along with the corresponding  carcinoma types are associated with HPV infections, most predominantly HPV 16.^4,5 Verrucous carcinoma is also associated with HPV, usually of type 6 or 11.^4,5

Persistent infection with high risk HPV infection  is a major risk factor for both vaginal intraepithelial neoplasia (VAIN) and SCC.⁴ The fact that VAIN and vaginal SCC are much less common than cervical neoplasia has been  explained by the absence of a vulnerable transformation zone in the vagina.⁴

CONCLUSION 

We conclude that strict adherence to the FIGO  guidelines is crucial in determining the primary site of gynecological cancers in patients  with advanced local disease. 

With per capita total expenditure on health of  US$8 per year in Nigeria⁵ and a retail price of up to $125 per dose or $375 for the full series consisting of 3 doses²⁸ it appears that HPV vaccines may be out of the reach of the average Nigerian and without  government funding, it may not be the ultimate solution for reducing the burden of disease  from anogenital cancers and other HPV-associated diseases at this time. 

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Clement A. Okolo, MBBS, FMCPath;¹ M. Olatokunboh Odubanjo, MBBS, FMCPath;¹* Olutosin A. Awolude, MBBS, FMCOG;² Effiong EU Akang, MBBS, FMCPath, FWACP¹

¹ Department of Pathology, University College Hospital, Ibadan, Nigeria
² Department of Obstetrics and Gynecology, University College Hospital, Ibadan, Nigeria 

*Corresponding Author: Dept  of Pathology, University College Hospital, Ibadan, Nigeria.
(Email: todubanjo2002@yahoo.com) 

CONFLICT OF INTEREST 

None of the authors has any conflict of interest  to declare. 

Go To | Top | Abstract | Text | Author Information | References |  

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REFERENCES 

Go To | Top | Abstract | Text | Author Information | References |

Juliana F. Yang, MD; Shou-jiang Tang, MD; Ruonan Wu, MSE; Qinghua Yang, MD, PhD*

Growing evidence shows that not only colorectal cancer (CRC) incidence but also its distribution patterns are changing. It is important to understand these changes to guide CRC screening, management, and public health strategies. We retrospectively analyzed the database of Miraca Life Sciences Research Institute for a one-year period (January 1 to December 31, 2009). We extracted all patients’ records with a diagnosis of CRC signed by all Miraca pathologists and compared with patients with a diagnosis of tubular adenoma (TA), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) signed by a single GI pathologist for diagnosis consistency during the same period. Patients’ age, gender, and anatomic locations were analyzed and mapped in the study. A total of 1,757 patients with CRC, 1,341 with TA, 199 with SSA/P and 36 TSA were studied. The distribution patterns of CRC and TSA showed a significant left-sided colon predominance (62.9% of CRC, p < 0.001; 76.3% of TSA, p = 0.013), especially in the sigmoid and rectum regions. In contrast, SSA/P showed a significant right-sided distribution pattern (67.9%, p < 0.001) and TA showed a slightly predominant toward the right-sided colon (53.1%, p = 0.041). Although the distribution pattern of CRC was left-sided predominant, it shifted toward right-sided colon among patients with advancing age and being female gender. This study indicates that dynamic shift of CRC from left-sided colon toward right-sidedness was largely due to patients’ advancing age and being female gender. The right-sided predominant distribution patterns of SSA/P might play an important role in the increased risk of right-sided CRC. Therefore, it is important to take extra effort to examine right-sided colon endoscopically in high risk patients.

Key Words: Colorectal cancer, anatomic distribution pattern, tubular adenoma, sessile serrated adenoma/polyp, traditional serrated adenoma

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Juliana F. Yang, MD;¹ Shou-jiang Tang, MD;² Ruonan Wu, MSE;² Qinghua Yang, MD, PhD³*

¹Department of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI
²Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS
³Miraca Research Institute, Miraca Life Sciences, Irving, TX

*Corresponding Author: Miraca Research Institute, Miraca Life Sciences, 6655 North MacArthur Boulevard, Irving, TX 75039. Tel: 214-596-2248.
(Email: qyang@miracaLS.com)

CONFLICTS OF INTEREST

The authors have no conflict of interest to disclose.

ABBREVIATION USED IN THIS PAPER

CRC, colorectal cancer; TA, tubular adenoma; SSA/P, sessile serrated adenoma/polyp; NOS, not otherwise specified.

AUTHORS CONTRIBUTIONS

Juliana Yang,MD: study concept, acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

Shou-jiang Tang, MD: study concept and design; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

Ruonan Wu, MSE: drafting of the manuscript; critical revision of the manuscript for important intellectual content.

Qinghua Yang, MD, PhD: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content.

FUNDING

No funding utilized.

ACKNOWLEDGEMENT

The authors greatly appreciate Ms. Karla Abila for searching and maintaining the database and Ms. Suzanne Ridner for providing valuable administrative support.

Bruno M?rkl, MD;* Tina Schaller, MD; Ines Krammer, MD; Claudio Cacchi, MD; Hanno Spatz, MD

Lymph node staging is still of crucial importance in rectal cancer. However, the recommendation to evaluate at least 12 lymph nodes for a sufficient staging is often not achieved in daily practice. This problem is even more pronounced after neoadjuvant treatment. The methylene blue assisted lymph node dissection technique (MBLND) has been shown to improve lymph node harvest in gastrointestinal cancers very effectively.
A retrospective analysis enrolling 54 cases was performed to investigate the effect of MBLND in neoadjuvantly treated rectal cancer cases. Two historical collections evaluated using conventional dissection technique (n = 47) and fat clearance (FC) technique, respectively served as controls (n = 12).
The lymph node harvest was highly significantly improved in the methylene group compared to fat clearance and conventional dissection with mean LN numbers of 29 ± 11, 21 ± 13, and 9 ± 4 (P < 0.001), respectively. Insufficient LN harvest occurred in 72 % of the control group cases, in 17 % of the FC-group and in no case of the Methylene group. Node positivity was found in 24%, 25% and 28% in the MB-, FC- and control group, respectively.
MBLND is a highly effective method guaranteeing an optimal lymph node harvest in colorectal cancer even under the difficult conditions of preoperative chemo-radiation. In our hands it was even more effective than a fat clearance technique.

Key Words: Lymph node, colorectal cancer, methylene blue, neoadjuvant

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Bruno M?rkl, MD;* Tina Schaller, MD; Ines Krammer, MD; Claudio Cacchi, MD; Hanno Spatz, MD

Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
Department of General, Visceral and Transplantation Surgery, Klinikum Augsburg, Augsburg, Germany

*Corresponding Author: Institute of Pathology, Klinikum Augsburg, Stenglinstrasse 2, 86156 Augsburg, Germany. Tel: 0049 821 4003199, FAX: 0049 821 400173199.
(Email: Bruno.Maerkl@klinikum-augsburg.de)

CONFLICT OF INTEREST

The authors have no conflict of interests to disclose.

ACKNOWLEDGEMENTS

The authors are thankful to Barbara Kresse and Kai-Uwe Hebick for the data management.

Chiung-Min Wang, BS; Wei-Hsiung Yang, PhD*

Cyclic AMP-dependent transcription factor-3 (ATF3),  a stress sensor and mediator, plays an essential role in cells to maintain homeostatsis and  has diverse functions in cellular survival and death signal pathways. Previously,  we demonstrated that ATF3 can be SUMOylfigated in vitro and in vivo and lysine 42 is the  main SUMO site. Several reports have shown that ATF3 is a novel regulator of p53 protein stability  and function; however, the role of ATF3 SUMOylation on ATF3-p53 interaction and p53 stability  as well as p53-dependent transcriptional activity remains unknown. Here we report that de-SUMOylation  of ATF3 enhanced ATF3-p53 physical interaction. While overexpression of ATF3 stabilizes p53,  SUMOylation status of ATF3 does not alter ATF3-mediated p53 stability. Interestingly,  de-SUMOylation of ATF3 augmented trans-activation of p53 responsive promoters, including  natural p53-dependent promoters. Taken together, we provide the evidence that SUMOylation  of ATF3 regulates ATF3-p53 interaction and transactivation of p53 responsive promoter. 

Key Words: ATF3, p53,  SUMO 

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Chiung-Min Wang, BS; Wei-Hsiung Yang, PhD*

Department of Biomedical Sciences, Mercer University  School of Medicine, Savannah, GA 

*Corresponding Author: Department  of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404.  Tel: (912) 350-1708.
(Email: yang_w@mercer.edu) 

CONFLICT OF INTEREST 

None. 

ACKNOWLEDGMENTS 

We would like to thank Dr. Tsonwin Hai for providing  the ATF3 plasmid, Dr. Chunhong Yan for providing the TP53-Luc (tandem repeats) plasmid,  and Dr. Hua Lu for providing the MDM2-Luc plasmid. We thank Dr. Buffy Ellsworth (Southern  Illinois University, Carbondale, IL) for critical reading and input. This work is supported  by a Mercer University Seed Grant (W.H.Y.) and a Larsen Research Endowment Fellowship? Program grant (W.H.Y.). 

This work is supported by a Mercer University  Seed Grant (W.H.Y.) and a Larsen Research Endowment Fellowship?Program grant (W. H.Y.). 

ABBREVIATIONS 

ATF3, cyclic AMP-dependent transcription factor-3/activating  transcription factor-3; p53, cellular tumor antigen p53; TP53, gene name for p53 protein;  SUMO, small ubiquitin-like modifier; SENP, sentrin-specific protease; PIAS3, E3 SUMO-protein  ligase PIAS3; CDKN1A, cyclin-dependent kinase inhibitor 1 (p21) 

Figure 1. Regression analysis with linear fit plot showed a strong correlation between MPY and FY for autologous PBSC patients mobilized by G-CSF and plerixafor.

Zhengtong Pei, MD;Shiyu Wang, BS; He Wang, MD, PhD*

Breast granular cell tumors are rare benign tumors  with clinical and radiological resemblance to mammary carcinoma. Definitive diagnosis usually  needs tissue or fine needle aspiration based cellular examination. Special stains,  including PAS, PASD, S-100 and CK, are very important for reaching the correct diagnosis.  However, the current markers to differentiate this tumor from histiocytes, including ¦Á-1-antitrypsin,  ¦Á-1-antichymotrypsin and CD68, are not very specific. Both ¦Á-1-antitrypsin and CD68 are  positive in our case. A more extensive panel of histiocytic markers should be tested to evaluate  their differential utility between histiocytes and GCTs, especially breast GCTs. 

Key Words: breast granular  cell tumors (GCTs); Alph-1 antitrypsin, immunohistochemistry, literature review 

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Zhengtong Pei, MD;¹Shiyu Wang, BS;² He Wang, MD, PhD³*

¹ Department of Pathology, Saint Barnabas Medical Center, Livingston, NJ
² The Commonwealth Medical College, Scranton, PA
3 Department of Lab Medicine and Pathology,  Beth Israel Medical Center, Newark, NJ 

*Corresponding Author: Department  of Lab Medicine and Pathology, Newark Beth Israel Medical Center, Newark, NJ.
(Email: he_wang_948@hotmail.com) 

CONFLICT OF INTEREST 

The authors declare that they have no competing  interests. 

Julie Chepovetsky, MD; S. Choo Yoon, MD;Amanda G Blouin, MD; Sharon Tindle;

Andrea Bertinelli, RN; Emeris Nash, RN; Ding Wen Wu, MD, PhD*

Autologous peripheral blood stem cell transplantation  is used to treat multiple hematologic malignancies including multiple myeloma, lymphomas and  amyloidosis. G-CSF plus plerixafor has increasingly become a viable first-line PBSC mobilization  option in the autologous patients. The aim of our study was to determine whether peripheral  blood CD34+ cell count (PB CD34) or midpoint collection CD34+ yield (MPY) is a better predictor  of the final collection CD34+ yield (FY) to guide decision-making to ensure collection target  achievement and, when possible, to reduce collection sessions for adult autologous PBSC patients  mobilized with both G-CSF and plerixafor. Eighty-eight autologous patients who were mobilized  by the 2-pronged regimen underwent 171 PBSC collection sessions in 2011. Retrospective data  analysis for the PBSC collections showed: (1) Both PB CD34 and MPY correlate strongly with  FY; (2) Reduction of apheresis sessions in 24 patients was achieved by decision-making based  on FY estimation using PB CD 34 and/ or MPY. Reduction of apheresis sessions decreases the  discomfort, inconvenience, cost, and time spent associated with the stem cell collection for  the patients, and also decreases the cost and increases the efficiency of our apheresis operation.  Based on the prediction value of either PB CD34 or MPY, a guideline is developed for our  apheresis facility for autologous PBSC patients, and 1 increased TBV is preferred at most  of the time. 

Key Words: Autologous peripheral  blood stem cell collection, Peripheral blood CD34+ cell count, Collection CD34+ yield,  Total blood volume, Collection efficiency 

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Julie Chepovetsky, MD;¹ S. Choo Yoon, MD;¹Amanda G Blouin, MD;¹ Sharon Tindle;¹ Andrea Bertinelli, RN;² Emeris Nash, RN;²Ding Wen Wu, MD, PhD¹*

¹Department of Pathology, Mount Sinai Medical Center, New York, NY
²Apheresis Center, Mount Sinai Hospital, New York, NY 

*Corresponding Author: Mount  Sinai Medical Center, Department of Pathology, One Gustave L. Levy Place, Box 1024,  New York, NY 10029. Tel: 212-241-3690, Fax: 212-876-5994.
(Email: dwwu5678@gmail.com) 

CONFLICT OF INTEREST 

The authors have no conflict of interest to disclose. 

FUNDING SOURCES 

Not applicable. 

ACKNOWLEDGMENTS 

The authors are indebted to the apheresis nursing  staff members for their carrying out all the stem cell collection procedures in the study.  We are grateful to Dr. Loraine Miller and her Flow Cytometry Laboratory staff members for  easy access and fast turnaround time of CD34 count tests in their Laboratory. We thank Ms.  Yelena Sinitsyn and her Cellular Therapy Laboratory staff members for their timely processing  PBSC collection products and for their prompt reporting the final collection CD 34 yield.