Anal Canal Tumors Research Articles

The Efficacy of Endoanal Sonography in Treatment of Patients with Anal Diseases Referred to Shiraz Colorectal Surgery (SCRS) Department Since 2011

Background/Objectives: Different diagnostic modalities have been used in treatment of patients with anal diseases who have referred to Shiraz colorectal surgery (SCRS) department in the past 7 years. These modalities include anoscopy, manometry, endoanal sonography, MRI and EMG in addition to clinical evaluation. Among these modalities, endoanal sonography looks like the first choice of SCR surgeons, and with their increasing reliance on ultrasound findings, the rate of using other modalities have declined among in recent years. Patients and Methods: To evaluate the efficacy of endoanal songraphy on treatment planning of patients with anal diseases, we reviewed the notes of patients who had anal sonography prior to treatment by using Medtronic 360 degree endoanal sonography device. We focused on decision making efficacy of this modality and its diagnostic accuracy. Results: Endoanal sonography was done in 1418 patients from March 2011 to December 2013. In 83% of patients anal canal structure was normal, and in 17% of patients, pathological findings such as anal canal tumor, peri-anal fistula and anal sphincter muscle damage were found. Comparing to other modalities, endoanal sonography had most accuracy in diagnosis of patients with fecal incontinence and was very helpful for colorectal surgeons in decision making for patients with anal canal tumors. In 5 patients with anal canal tumor, primary decision of local excision was changed to AP resection because of detecting T2 or T3 involvements. In 2 patients who insisted on local excision, deep tissue involvement was revealed on histopathology. In patients with incontinence due to sphincter damage, the detected site of damage was accurate in 100% of patients, and colorectal surgeons could confidently rely on sonography findings for approach to the site of sphincter defect. In 15 patients with longstanding anal pain, a small peri-anal cold abscess was detected on endoanal sonography. These abscesses had not been diagnosed prior to ultra sound scanning and were eventually approached and treated under the guide of sonography. Conclusion: Endoanal sonography can be the best modality in detection of anal canal diseases if there is close cooperation between radiologists and colorectal surgeons.

Anal Cancer Study Based on Korea Central Cancer Registry Data: One Step Forward in Clinical Research

See Article on Page 182-185 First of all, I would like to congratulate the authors of this work, which focused especially on rare tumors and anal cancer based on National Cancer Registry data. For colorectal surgeons, knowledge of oncologic outcomes for anal cancer is important for making a therapeutic decision. Furthermore, these outcomes should be based on Korean Cancer Registry data. Anal cancer constitutes a relatively small portion of gastrointestinal tract cancers [1]. However, anal cancers are probably underreported because some anal canal tumors are misclassified as rectal tumors. Wide geographical and racial variations in the incidence of cancers are observed around the world. The incidence and the survival rates are generally well publicized for the more common cancers, such as lung, breast, and colorectal tumors; however, little is written regarding the incidence and the survival rates for anal canal cancer. Although some authors have reported clinicopathologic features or prognostic factors for anal cancers [2, 3], the characteristics of and the survival rate for anal cancer in Korea are largely unknown because no population-based study has been performed to address these issues in Korea. For decades, in many countries and regions, registration of cancers has been mandatory. National cancer registration is rooted in public health, helps in the planning of health services, and can be an important tool in clinical research. However, sometimes clinicians are frustrated because the cancer registry cannot provide all the information they need. A limitation in this study based on Korea Central Cancer Registry data is that the database lacks information on interventions such as surgery, radiation, and chemotherapy, on time to any type of recurrence, or on aspects of quality of care for anal canal cancer. The authors compared the survival between males and females by Surveillance, Epidemiology and End Results (SEER) stage and found that survival rates showed a diffference according to sex and age which was related to the distinct features of Korean patients with anal cancer [4]. This study is the largest to date that reports population-based survival data for anal canal cancer in Korea, and it provides an updated picture of anal canal cancer during the past 17 years. Even though the results could be representative of the population in Korea and should be more meaningful than single-institution experiences, this study has some limitations. The study did not analyze oncologic oucomes according to TNM stage, therapeutic modality, or recurrence pattern. In the future, the detailed parameters must be checked before analyzing Korean Cancer Registry database. Additionally, current data needs to be compared with published single-institution anal cancer data. Finally, prospective multicenter studies based using clinical databases on rare cancers need to be done to improve the quality of the data.

Two cases of early squamous cell carcinoma of the anal canal (tumor <i>in situ</i>) diagnosed by magnifying endoscopy with narrow band imaging

Two cases of early squamous cell carcinoma of the anal canal (tumor <i>in situ</i>) diagnosed by magnifying endoscopy with narrow band imaging

Double anal canal cancers associated with a long history of perianal Paget’s disease: report of a case

Extramammary Paget's disease (EPD) is rare. We report a case of double anal canal cancers in a patient with a long history of perianal Paget's disease. The patient, a 68-year-old Japanese woman, refused surgery initially and was treated with electron beam therapy, which achieved remission. However, 6 years later, Paget's disease was found to be progressing again and double anal canal tumors were also detected in the proctos and external skin area. We performed abdominoperineal resection (Miles' operation) and lymph node dissection for the Paget's disease with double anal canal tumors. Immunohistochemical staining revealed cytokeratin (CK)-20 expression in the adenocarcinomas and Paget's disease lesion, but not CK-7 or gross cystic disease fluid protein-15 expression. The lesion was joined to the carcinoma by a stalk. The immunohistochemistry results suggested secondary EPD, although it was originally considered to be Paget's carcinoma (primary EPD) based on the clinical history.

Malignancies of the anal canal

The carcinomas of the anal canal consist of truly rare clinical entities compared to the most common colorectal malignancies. Consequently, little have been reported on their natural history and course. The present study is aiming to describe the experience of our clinic with anal cancer and to clarify the incidence of the disease in the Hellenic population. A 5-year retrospective study was conducted. We searched all cases of patients, diagnosed with anal carcinoma in our medical center. Medical records and histological examination results were all thoroughly registered and evaluated. On the whole, 60 patients were diagnosed with a malignant tumor of anal canal. Among them, 25 cases involved anal adenocarcinoma, 26 cases referred to a squamous cell carcinoma and in 5 cases, Bowen disease was identified. Two melanomas, one GIST stromal tumor and one case of Paget disease, were recognized as well. It seems that in our center the frequency and prevalence of anal adenocarcinoma is increased compared to the results from international data. More studies involving larger series of patients are required in order to shed further light in the true incidence of anal cancer and it subtypes in Hellenic population.

Four decades of anal cancer in Tasmania, Australia: what do the case data tell us?

Anal cancer is a rare cancer analogous to cervical cancer, largely caused by exposure to oncogenic human papillomavirus. We have sought to study this disease in the epidemiologically distinct population of Tasmania. Medical records at all tertiary and secondary referral centres in Tasmania were audited for records with corresponding International Classification of Diseases (ICD)-10 codes. Statistical significances of trends were evaluated using Fisher's exact test, logistic regression or linear regression. Of ~1350 screening records, 170 cases of anal cancer were found with patient presentation during 1973-2010, corresponding to 132 patients. This cohort was mostly female (66.7%), with squamous cell histology (81.8%) and anal canal primaries (72.0%). Most cases were detected at Stage II or below and the majority remained disease-free after treatment. Relatively few cases had documentation of typical risk factors for anal cancer, such as HIV seropositivity, a history of cancer or smoking. After 2000, there was a trend towards a lower stage at presentation, correlating with an increased 5-year survival. After 2000, no anal margin tumours presented beyond Stage II; nearly half were detected in situ and none were fatal. For anal canal tumours, there was virtually no change in the mean stage at detection or in survival. This is the first case series of anal cancer in Tasmania. We find that in many ways, including symptoms and pathology at presentation, epidemiology is typical. However, our cohort is distinct in its paucity of known risk groups, including HIV-positive people, those with a history of cancer and smokers.

Is the Centralized Treatment of Small Cell Carcinoma of Anal Canal Necessary? A Case Report

Anal canal tumor has different prognosis depending on the histological type. Cancer of the anal canal is an uncommon condition in digestive tumors, representing small cell cancers of the anal canal less than 0.2% of all colorectal tumors. The histological type of tumors of the anal canal will determine treatment and prognosis. We report the case of a male aged 71 who presented with rectal bleeding and constipation. It revealed a tumor 2 cm from the anal margin, with pathological diagnosis of small cell undifferentiated carcinoma. Despite treatment with chemotherapy and radiotherapy, the disease progressed to develop multiple metastases, and the patient died due to pulmonary thromboembolism and multiorgan failure. Centralized management of these tumors would allow the creation of specific guidelines for treatment and follow-up with the aim of achieving better morbidity and mortality rates.

An Update on Tumors of the Anal Canal

The anal canal possesses complex anatomy and histology and gives rise to a variety of tumor types. Challenging issues remain with regard to both the pathologic diagnosis and the clinical management of these tumors. To provide an updated overview of the histogenesis, clinical and pathologic characteristics, diagnostic terminology, and relevant clinical management of the various types of anal canal tumors. Recent literature on clinical and pathologic characteristics of anal canal tumors. Although most anal canal tumors are of squamous lineage, a complex variety of other tumors also occurs. Recognition of such diverse tumor entities will allow accurate pathologic diagnosis and most optimal clinical management.

Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

BackgroundWith the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas.MethodsFormalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers.ResultsEGFR immunoreactivity was present in 36/43 (83.7%) of anal canal and in 20/24 (83.3%) of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23), but could be identified in 4 of 24 tonsil tumours.From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified.ConclusionEGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified. This indicates that EGFR and K-RAS mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in anal canal and tonsil squamous cell carcinoma.

Laparoscopic abdominoperineal resection revisited: are there any health–related benefits? A comparative study

Laparoscopic colectomy is associated with less overall morbidity and improved survival for patients with colonic cancers. There are unfortunately limited clinical reports on laparoscopic abdominoperineal resection. We therefore designed this study to compare laparoscopic abdominoperineal resection with conventional open surgery, with emphasis on health-related issues from the patients' perspective in order to justify its role in the management of low rectal or anal canal tumours. We carried out a non-randomized, prospective comparative study on a cohort of patients who underwent either laparoscopic or open abdominoperineal resection between March 1994 and December 2003. Patient demographics, tumour characteristics, operative morbidity and mortality, as well as overall survival were considered. The standard endpoints of last follow-up date and deaths were used. Data was analyzed according to intention-to-treat principle. A total of 102 patients were recruited: 31 patients underwent conventional open abdominoperineal resection (OAPR) and 71 patients were treated laparoscopically. Patient demographics, median follow-up period, as well as tumour characteristics were similar between groups. The median operating time was similar among groups (145 min in laparoscopic group vs. 156 min in open group; p=0.62). Patients in the laparoscopic group had significantly less blood loss (p=0.01) and fewer requirements for blood transfusion (p=0.01). Despite similar overall morbidity, the laparoscopic group had a reduced incidence of abdominal wound infections (p=0.01) and chest infections (p=0.01). Overall survival was significantly better in the laparoscopic group (p=0.01). Laparoscopic abdominoperineal resection confers definite health-related benefits the over open approach in terms of reduced septic complications and fewer requirements for blood transfusion. It should be considered the procedure of choice for patients with low rectal or anal canal tumour in whom sphincter excision proved inevitable.

Tumours of the anal canal

Summary Anal canal pathology, particularly infections and tumours, has recently come into prominence, mainly because of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. This review provides a framework for diagnostic pathologists who may encounter anal canal tumours. A summary of embryology, anatomy and terminology is provided by way of background. Important points of distinction between the surgical, anatomic and histologic anal canal are highlighted. Squamous carcinomas and their precursor lesion, anal intra-epithelial neoplasia, are the most common primary epithelial abnormalities seen in the anal canal. In addition, there is a predilection for HIV-positive homosexual men with co-existent human papillomavirus (HPV) infection to develop squamous carcinomas. The more proximal the tumour is in the anal canal, the greater the association with basaloid morphology and HPV infection. Adenocarcinomas are uncommon and may arise from the anal transitional zone, anal glands or fistulous tracts, which may or may not be associated with long-standing Crohn's disease. The immunohistochemical profiles and separation from morphologically similar tumours are provided in this article. In addition, the role of new molecular markers is discussed in relation to tumour behaviour and therapeutic options.

The management of anal carcinoma.

In a 20-year survey of anal carcinoma at Groote Schuur Hospital 55 cases were studied retrospectively. Patients of mixed race with anal margin carcinoma had a median age 29 years below that of Whites with anal margin carcinoma. Patients in these two groups with anal canal carcinoma had the same median age. Anal margin tumours were smaller than anal canal tumours at presentation and had a substantially better 5-year survival rate. The approach to treatment of these conditions is outlined.

Tumor Site Predicts Outcome After Radiochemotherapy in Squamous-Cell Carcinoma of the Anal Region: Long-Term Results of 101 Patients

This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival. Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the anal margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26-84) years. T categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m (2)/day as 120 hours of continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10 mg/m (2)/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1-16) years. Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (< or =75 percent vs. >75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival. With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.

38 Brachytherapy in anal canal and rectal tumours

38 Brachytherapy in anal canal and rectal tumours

The impact of PET-CT fusion on radiation treatment planning in patients with gastrointestinal tumors

3636 Background: From 03/03 to 11/03, we prospectively evaluated the impact of PET scans on radiation treatment volumes when compared to CT scans in 25 patients with Gastrointestinal (GI)tumors. Methods : 18 patients were scanned on our GE Big Bore PET-CT scanner(PET aperture 70cm) and 7 on our standard aperture GE-PET-CT scanner. CT-PET images were automatically registered with PET-CT fusion software. Primary site was esophageal in 5, rectal in 18 and anal canal in 2 patients. Patients with rectal cancer received preoperative chemoradiation and all others received definitive chemoradiation. All patients were immobilized and scanned in treatment position and received 3-D conformal radiation . We are reporting findings in 18 of the 25 patients. One physician contoured CT Gross Tumor Volume(CT-GTV) and then the PET Gross Tumor Volume(PET-GTV). The PET and CT volumes were measured in cubic centimeters and percent overlap volume (POV) was analyzed. Results : In esophageal cancer patients the POV ranged from 20%–61%(mean 42.25%). In the 12 patients with rectal cancer, POV ranged from 11%–69%(mean 40.25% ). In patients with anal canal tumors, POV was 59%–99%(mean79%) . In 4/18 patients(22%), PET resulted in a change in the treatment planning volume; 2/4(50%)esophageal, 1/2(50%) anal canal and 1/12(8%)rectal tumors. In 30% to 80% of patients, PET suggested additional volume of tumor compared to CT alone. Conclusion: The addition of PET-CT fusion to the treatment planning process in GI tumors is important. The variation in volume was significant in 22% of patients resulting in a change in the treatment fields. The wide variation in tumor volume could have important implications in IMRT treatment planning where tighter margins are often used. We have obtained post treatment PET-CT scans in patients with rectal cancer and are correlating the findings with post resection pathological specimens. The sensitivity of PET-CT after chemoradiation will be discussed. No significant financial relationships to disclose.

Carcinome neuroendocrine à petites cellules de la région anorectale : à propos de deux cas

Introduction. – Anorectal neuroendocrine small cell carcinomas are rare and frequently difficult to treat. Exegesis. – Two women presented with a fungating tumor located on the upper part of the anal canal. Histology displayed neuron-specific enolase and chromogranin A immunoreactive small cell tumors. A plasmatic neuron-specific enolase secretion was noticed in one case. Tumors were poorly reactive to chemotherapy and irradiation, less than in usual epidermoid anal canal cancer. Evolution was quickly leading to hepatic and pulmonary metastases in both cases. Conclusion. – Anorectal neuroendocrine small cell carcinomas are rare but need to be individualized from epidermoid anal canal tumors owing to their poor prognosis with a frequent occurrence of hepatic and pulmonary metastasis.

Anal gland carcinoma.

Anal gland carcinoma is a rare entity. The authors conducted a joint study of cases coded as definite or possible anal gland carcinoma from the archives of the Armed Forces Institute of Pathology and the Canadian Reference Center for Cancer Pathology. Seven cases of potential anal gland carcinoma were identified from the Canadian files and 12 from the Armed Forces Institute of Pathology archives. Of these 19 cases, 14 had adequate material to allow clinical, histologic, and immunohistochemical analysis. Seven of these 14 cases met a modified World Health Organization (WHO) definition of anal gland carcinoma. The mean age of these patients was 66 years (range, 60-72 years), with a male-to-female ratio of 6:1. The tumors were composed of haphazardly dispersed, small glands with scant mucin production that invaded the wall of the anorectal area with no obvious intraluminal component observed clinically or microscopically. Immunohistochemical studies were performed on all seven of these cases, revealing cytokeratin (CK) 7+/CK 20- expression in six cases, and CK 7+/CK 20+ expression in one case. The remaining seven cases showed no intraluminal component but did not meet a modified WHO definition of anal gland carcinoma. This group included three mucinous adenocarcinomas (two clinically arising in anal fistulas), all of which were CK 7+/CK 20+, and a rectal-type adenocarcinoma that was CK 7-/CK 20+. There was also a tumor interpreted as probable rectal-type adenocarcinoma that was CK 7+/CK 20+, and a tumor interpreted as probable squamous cell carcinoma that was CK 7-/CK 20-. The seventh tumor in this group, which could not be classified, was CK 7+/CK 20-. A useful and discriminating definition of anal gland carcinoma is an anal canal tumor composed of haphazardly dispersed, small glands with scant mucin production invading the wall of the anorectal area without an intraluminal component. The glands are positive for CK 7.

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.

In vitro radiosensitivity of skin fibroblasts can identify a group of patients with complications in various health tissues after radiotherapy

A retrospective study of the in vitro radiosensitivity of skin fibroblasts derived from two groups of patients treated by definitive radiotherapy for a variety of tumors who either displayed or did not display severe complications. Seven radiotherapy patients were selected: three were treated for head and neck, prostate and non-Hodgkin lymphoma tumors, and did not develop any significant complications (control group); four patients were treated for bladder, thyroid, head and neck and anal canal tumors and developed serious acute and especially late reactions (hypersensitive group). Primary cell cultures of skin fibroblasts were established and their radiosensitivity studied by the clonogenic assay after exposing to single radiation doses ranging between 1 and 8 Gy. The survival fraction at 2 Gy (SF2) ranged from 0.27 to 0.38, with a mean of 0.33 for the control group, and from 0.10 to 0.20 with a mean of 0.17 for the hypersensitive group. The Mann-Whitney non-parametric test showed that the difference between the two means was statistically significant (p = 0.03). The data are in favor of a correlation between the radiosensitivity of patients' fibroblasts and the reactions of different normal tissues to radiotherapy. This association supports the use of the clonogenic survival, or a surrogate test, as a predictive assay. The multiplicity of normal tissues and organs implicated in this association suggests the existence of genetic factors that determine, at least in part, the radiosensitivity of target cells involved in the expression of normal tissues complications following radiotherapy.

Trans anal full thickness tru-cut needle biopsies in anal canal tumors after conservative treatment.

After conservative treatment anal mucosal biopsies enable exclusion of neoplastic cells only on the endoluminal surface. We used transanal full thickness tru-cut needle biopsies in the follow-up of 11 anal tumors. Full thickness tru-cut needle biopsies showed malignant cells in the fibrous tissue in 3 patients and few cells with atypical nuclear features in another 2. All diagnostic exams resulted negative. Therefore, needle biopsies were helpful to diagnose neoplastic remainder. Multiple samples are necessary to reduce the false negative number. This method is simple, relatively inexpensive, easily repeatable and not burdened with complications.