Anal Tumors Research Articles

Редкие злокачественные новообразования в практике онкопроктолога: ретроспективный анализ опыта клиники за 20 лет

Abstract. Rare malignant tumors require complex diagnostics and extended multidisciplinary team discussion. Knowing rare tumours epidemiology is vital for correct organization of clinical work in different departments. The aim of this study was to investigate epidemiological data on rare colorectal and anal malignant tumors in a large-volume tertiary hospital. Methods. A retrospective analysis was carried out in N.N. Blokhin Russian Cancer Research Center during 2000-2020. All patients (both in- and outpatient departments) with colorectal and anal tumors were identified. Rare colorectal and anal malignant tumors were identified using an ICD-X and ICD-O codes. We investigated the incidence of identified tumors. Results. 22 801 unique patients were identified in the registry, 15 490 (67,9%) had malignant tumors. 1443 (9,3%) had rare malignant tumors: squamous-cell cancer in 649 (45%), neuroendocrine tumors in 277 (19%), signet-cell carcinoma in 193 (13%), lymphomas in 119 (8%), melanomas in 83 (6%), sarcomas in 72 (5%), GIST in 22 (2%), other rare tumors in 22 (2%). Conclusions. The burden of rare malignant tumors is high in clinical practice of colorectal cancer specialists. Specialized multidisciplinary teams and referral systems are necessary to improve the quality of care.

Rare, benign, giant anal tumor in a healthy woman

Anal neoplasms are frequently associated with human papillomavirus infection. However, the differential diagnosis should consider benign lesions that affect a small proportion of patients. We present the case of a previously healthy 30-year-old woman who presented to our clinic with the complaint of a foreign body sensation in the perianal region and a progressive increase in the volume of a palpable lesion. The patient underwent resection of the lesion and histopathological examination showed a benign giant fibroepithelial polyp.

Radiodermatitis: severity, predictive factors and discontinuation of radiotherapy in patients with anal and rectal cancer.

to determine the prevalence of radiodermatitis, severity grades and predictive factors of its occurrence in patients with anal and rectal cancer followed up by the nursing consultation, and to analyze the association of severity grades of radiodermatitis with temporary radiotherapy interruption. a quantitative, cross-sectional and retrospective study, carried out with 112 medical records of patients with anal and rectal cancer undergoing curative radiotherapy followed up in the nursing consultation. Data were collected using a form and analyzed using analytical and inferential statistics. 99.1% of patients had radiodermatitis, 34.8% of which were severe. The predictive factors were female sex, age greater than 65 years, anal canal tumor, treatment with cobalt device and IMRT technique. Treatment interruption occurred in 13% of patients, associated with severe radiodermatitis. there was a high prevalence of radiodermatitis, mainly severe, which resulted in treatment interruption.

Systemic Delivery of a Dual PI3K/mTOR Inhibitor More Effective than Topical Delivery in Preventing Anal Carcinogenesis in an HPV Transgenic Mouse Model.

Anal dysplasia is a growing health concern that over time can result in squamous cell carcinoma (SqCC) of the anus. In this study, we compare a topical versus systemic (oral) administration of LY3023414, a dual PI3K/mTOR inhibitor, to prevent anal carcinogenesis in a Human Papillomavirus (HPV) mouse model of anal cancer. K14E6/E7 transgenic mice were used to model HPV-induced anal carcinogenesis. Mice with varying starting anal histologies (normal histology, low-grade, and high-grade anal dysplasia) were treated topically at the anus or systemically via oral gavage with LY3023414 with or without topical carcinogen for 20 weeks. Mice were monitored for overt anal tumor development and anal tissue was assessed for histology and markers of PI3K and mTOR activity (pAKT and pS6, respectively). LY3023414 treatment, regardless of the mode of delivery, significantly decreased overt tumor development in mice starting with normal histology and low-grade anal dysplasia. Systemic LY3023414 treatment was more effective in delaying tumor onset than topical treatment. Mice treated with systemic LY3023414 had significantly reduced rates of anal SqCC when starting with normal and low-grade anal dysplasia compared to topical treatment. Topical treatment was only effective in reducing SqCC in the setting of low-grade dysplasia. LY3023414 inhibition of pAKT and pS6 expression varied with starting histology. Neither treatment mode was effective in the setting of high-grade anal dysplasia. Systemic LY3023414 treatment was more effective than topical application in delaying the progression of normal anal histology and low-grade dysplasia to anal cancer in HPV-associated mice.

Endoscopic submucosal dissection for rectal neoplastic lesions: experience from a European center.

IntroductionNowadays, various endoscopic resections including polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) are well known first-line approaches for early neoplastic rectal tumors.Material and methodsIn this case series study, we analyzed 320 ESD procedures performed in a high-volume colorectal center in Poland, Europe. The aim of this study was to retrospectively evaluate ESD procedure in cases of rectal carcinoma performed by a single trained operator in a referral center provided with endoscopy.ResultsOverall, en bloc resection was observed in 92.5% of patients (296/320). The en bloc resection rate was at a similar level in those lesions with involved anal sphincters versus tumors without involvement (93.85% vs. 92.16%; p=0.644). R0 resection was noted in 89.4% of patients (286/320). The overall curative ESD rate was 85.94% (n=275). The curative ESD rate in the invasive cancer group reached 52.6% (n=20). We observed ESD-related adverse events, such as bleeding and perforation, in 3.4 % of patients (n=11).ConclusionsWe have demonstrated that ESD in rectal tumors is an efficient and safe procedure with a high curative rate, even in difficult lesions. Anal sphincter localization and recurrent character of the lesion have no impact on the final outcomes. The ESD approach should have been considered for all rectal tumors, especially those lesions suspected of superficial mucosal invasion, as it can serve as a staging method and may have been curative for adenomas and cancers limited to mucosa.

Deep learning-based automatic delineation of anal cancer gross tumour volume: a multimodality comparison of CT, PET and MRI

Background Accurate target volume delineation is a prerequisite for high-precision radiotherapy. However, manual delineation is resource-demanding and prone to interobserver variation. An automatic delineation approach could potentially save time and increase delineation consistency. In this study, the applicability of deep learning for fully automatic delineation of the gross tumour volume (GTV) in patients with anal squamous cell carcinoma (ASCC) was evaluated for the first time. An extensive comparison of the effects single modality and multimodality combinations of computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have on automatic delineation quality was conducted. Material and methods 18F-fluorodeoxyglucose PET/CT and contrast-enhanced CT (ceCT) images were collected for 86 patients with ASCC. A subset of 36 patients also underwent a study-specific 3T MRI examination including T2- and diffusion-weighted imaging. The resulting two datasets were analysed separately. A two-dimensional U-Net convolutional neural network (CNN) was trained to delineate the GTV in axial image slices based on single or multimodality image input. Manual GTV delineations constituted the ground truth for CNN model training and evaluation. Models were evaluated using the Dice similarity coefficient (Dice) and surface distance metrics computed from five-fold cross-validation. Results CNN-generated automatic delineations demonstrated good agreement with the ground truth, resulting in mean Dice scores of 0.65–0.76 and 0.74–0.83 for the 86 and 36-patient datasets, respectively. For both datasets, the highest mean Dice scores were obtained using a multimodal combination of PET and ceCT (0.76–0.83). However, models based on single modality ceCT performed comparably well (0.74–0.81). T2W-only models performed acceptably but were somewhat inferior to the PET/ceCT and ceCT-based models. Conclusion CNNs provided high-quality automatic GTV delineations for both single and multimodality image input, indicating that deep learning may prove a versatile tool for target volume delineation in future patients with ASCC.

Sex-dependent development of Kras-induced anal squamous cell carcinoma in mice.

Anal squamous cell carcinoma (SCC) will be diagnosed in an estimated 9,080 adults in the United States this year, and rates have been rising over the last several decades. Most people that develop anal SCC have associated human papillomavirus (HPV) infection (~85–95%), with approximately 5–15% of anal SCC cases occurring in HPV-negative patients from unknown etiology. This study identified and characterized the Kras-driven, female sex hormone-dependent development of anal squamous cell carcinoma (SCC) in the LSL-KrasG12D; Pdx1-Cre (KC) mouse model that is not dependent on papillomavirus infection. One hundred percent of female KC mice develop anal SCC, while no male KC mice develop tumors. Both male and female KC anal tissue express Pdx1 and Cre-recombinase mRNA, and the activated mutant KrasG12D gene. Although the driver gene mutation KrasG12D is present in anus of both sexes, only female KC mice develop Kras-mutant induced anal SCC. To understand the sex-dependent differences, KC male mice were castrated and KC female mice were ovariectomized. Castrated KC males displayed an unchanged phenotype with no anal tumor formation. In contrast, ovariectomized KC females demonstrated a marked reduction in anal SCC development, with only 15% developing anal SCC. Finally, exogenous administration of estrogen rescued the tumor development in ovariectomized KC female mice and induced tumor development in castrated KC males. These results confirm that the anal SCC is estrogen mediated. The delineation of the role of female sex hormones in mediating mutant Kras to drive anal SCC pathogenesis highlights a subtype of anal SCC that is independent of papillomavirus infection. These findings may have clinical applicability for the papillomavirus-negative subset of anal SCC patients that typically respond poorly to standard of care chemoradiation.

Posttreatment FDG-PET-CT Response via PERCIST Criteria is Predictive of Tumor Prognosis in Anal Carcinoma

We hypothesize that posttreatment F-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is useful to evaluate metabolic response in patients with anal cancer, specifically via the Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST).This was a single-institution retrospective review of 62 patients treated with Nigro Regimen chemoradiation therapy for anal squamous cell carcinoma between 2008 and 2020. All patients had pretreatment PET-CT scan and were followed with posttreatment PET-CT scans and clinical examinations. PERCIST criteria was utilized to evaluate the treatment response to chemoradiation therapy. If a target lesion shows complete resolution of FDG uptake, the response is complete metabolic response (CMR). If the decrease from baseline to follow-up is greater than or equal to 30%, the response is partial metabolic response (PMR). If the decrease is less than 30% or if the lesion shows an increase of FDG uptake less than 30%, the response is stable metabolic disease (SMD). If the target lesion shows a 30% increase or higher FDG uptake, or if there is a new lesion, the response is disease progression (DP).The median follow-up was 38 months (range, 7-114 months). Pretreatment PET-CT detected the primary tumor in 62 cases (100%), the inguinal lymph nodes were FDG avid in 33 patients, and the pelvic lymph nodes were FDG avid in 39 patients. Initial posttreatment PET-CT was obtained on average 3 months after the last day of radiation. The evaluation of the primary anal tumor on initial follow-up PET-CT showed CMR in 31 patients (50%), PMR in 26 patients (42%), and SMD in 5 patients (8%). No patients showed disease progression (DP, 0%). The evaluation of the largest inguinal node on initial post treatment PET-CT showed CMR in 30 patients (91%), PMR in 3 patients (9%), without evidence of progression of groin lymphadenopathy. The evaluation of the largest pelvic node on initial post treatment PET-CT showed CMR in 36 patients (92%), PMR in 1 patient (3%), and SMD in 2 patients (5%), without evidence of progression of pelvic lymphadenopathy.The PERCIST criteria is a reliable and useful technique in evaluating treatment response for the primary anal cancer as well as the inguinal and pelvic lymphadenopathy. The Nigro protocol is a promising combined chemoradiation therapy strategy for the anal cancer patients with most demonstrating complete metabolic response or partial metabolic response on the initial post treatment FDG PET-CT scan.

Anorectal and perineal pain

Anorectal and perineal pain Abstract. Anorectal pain is a common clinical challenge in the outpatient office. Anal fissures, anal venous thrombosis, proctitis or neoplasms are frequent etiologies for proctalgia. After exclusion of somatic disorders by diagnostic imaging and endoscopy, functional anorectal pain or pathologies like interstitial cystitits, chronic prostatitis, coccycodynia or pudendal neuralgia should be considered. The Rome IV criteria distinguish proctalgia fugax, a sharp paroxysmal pain lasting for maximum 30minutes, and the levator ani syndrom. Latter is characterized by a tender puborectal muscle on digital rectal examination and pain lasting for more than 30minutes. Treatment consists in reassurance, sitz bathes, topical vasodilators and anal massage. Biofeedback is a further option for levator ani syndrome. Painful palpation of the ox coccygis leads to the diagnosis of coccycodynia, a non-functional disorder. Therapy consists in anti-inflammatory medications, os coccygis mobilisation and infiltration therapy. Urologic chronic pelvic pain (chronic prostatitis and interstitial cystitis) as well as pudendal neuralgia, both neurogenic pelvic pain syndromes, can cause pain radiating into the after and perineum. The diagnosis and discrimination from functional rectal pain is difficult. Patients with neurogenic anorectal pain are best treated with anti-inflammatory medications, pain modulating antidepressives, anticonvulsives or local infiltration therapy. Interdisciplinary management of complex pain patients is mandatory.

Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer

A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0=42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3=45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

Anorectal Melanoma-Brownish Black Mass Not Always a Hemorrhoid.

The non-specific clinical symptoms of anorectal brownish-black mass do not help to differentiate colorectal cancer, hemorrhoids, rectal ulcers which result in a delayed diagnosis or lead to inadequate management of lethal anorectal melanoma. Primary malignant melanoma of the anorectal region is an uncommon tumor, constituting approximately 1% of anal canal tumors which may be misdiagnosed clinically as hemorrhoids. Because of aggressive behavior and poor prognosis, efficient and prompt diagnosis is required in these cases. We report 2 cases of this rare tumor.

P-275 Evaluation of radical chemoradiation outcomes in stage II/III anal cancer: Real-world data population

Squamous cell carcinoma of the anus (SCCA) is a rare disease accounting for 1%–2% of digestive tract tumours and 2%–4% of colon, rectal and anal tumours. The annual incidence is 1 in 100 000, is higher in women and is increasing. Five-year survival has changed little in the last two decades. In the United States, the overall 5-year survival rates for 1994–2000 were 60% for men and 78% for women (SEER data). In Europe, 5-year survival varied between 66% (Central Europe) and 44% (Eastern Europe). Combinations of 5-fluorouracil (5-FU)-based radical chemoradiation (CRT) and other cytotoxic agents [mainly mitomycin C (MMC)] have been established as the standard of care, leading to complete tumour regression in 80%–90% of patients, with locoregional failures of ∼15%. Approximately 10%–20% of patients suffer distant relapse. The aim of this study was to evaluate outcomes in stage II/III anal cancer submitted to CRT. A retrospective analysis evaluated stage II-III SCCA pts with PS ECOG 0-1 treated with CRT using fluoropyrimidine and MMC at a single Portuguese Oncology Unit between January 1st 2010 and October 30th 2020. Data cut-off was March 20th 2021. Data were obtained from pts´ clinical files and analysed with SPSSv26.0. Twenty-three pts were selected with a median (med) age of 66 years (y) [30-81], the majority being females (60.9%). Regarding initial staging, 21.7% had stage II, 17.4% stage IIIA, and 60.9% stage IIIB. 39.1% were active smokers; 56.5% were tested for HIV infection, of whom 3 were HIV positive. 78.3% had lymph node disease; 47.8% had tumours > 5 cm in size; 56.5% had ulcerated lesions (skin or endoscopically). Of the 23 pts, 2 (8.7%) were treated with capecitabine (CAP), while the others were treated with infusional 5-FU in addition to MMC. There was an imaging and endoscopic complete response (CR) in 78.3% of the pts (including both pts treated with CAP); 3 of the 5 pts without CR underwent salvage surgery. 13% had locoregional relapse and 4.3% had distant relapse. Med follow-up was 4y; the overall survival at 4y was about 75%, with an estimated med OS 8.09y [6.0-10.2]. In our cohort, CRT was associated with a higher CR rate in concordance with previous evidence. Distant relapse was slightly inferior in our population. Going forward, we will be studying prospective data on the use of CAP vs infusional 5-FU in CRT-treated patients. Given the rarity of this diagnosis and the lack of evidence on this subject, we believe our findings are of extreme importance to share.

P-214 Should patients with active gastrointestinal tumors receive thromboprophylaxis to avoid the negative clinical consequences of CAT? Sub-analysis of ACT4CAT study

Cancer Associated Thrombosis (CAT) causes many complications in cancer patients. There is a need for thrombosis assessment and management during the cancer patient's journey due to the dynamic nature of the disease. Especially gastrointestinal (GI) cancers have a high thrombotic burden. Anticoagulant agents are of great importance for the prevention and treatment of thrombosis, mainly with Low Molecular Weight Heparins (LMWHs). ACT4CAT is prospective observational study conducted by HeSMO, aiming to record clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high thrombotic burden patients with active cancer who received thromboprophylaxis enrolled after signing informed consent were enrolled. Across Greece, 18 oncology departments recruited 431 patients; 177 (41.1%) had GI tumors; of these, 120 completed the study. Tumor types: 92 pancreatic (52.0%), 49 colorectal (27.7%), 30 gastric (17.0%) and 6 others (3.3%, 4 cholangiocarcinomas, 1 GIST, 1 anus). Patient demographics: 58.8% ≥65 years old, 33.3% were females and average BMI 25.6±8.6 Kg/m2. Metastatic disease occurred in 84.1% of patients. Regarding clinical setting: 3.5% adjuvant, 8.1% neoadjuvant, 63.2% 1st line, 17.2% 2nd line, and 8% other. 96.6% of patients received Highly Thrombogenic Agents (HTAs) (90% of gastric, >98% of pancreatic and colorectal, p=0.0302), e.g. platinum (51.4%), antimetabolites (91.0%). Anticancer treatment had the potential for drug-drug interactions with oral anticoagulants in 45.2% of patients with higher percentage in pancreatic tumors (62.0%, p Anticoagulant agents reported: tinzaparin 93.2%, fondaparinux 2.3%, bemiparin 1.7%, enoxaparin 1.1%, apixaban 0.6%. Intermediate doses administered in 63.3% and therapeutic doses in 9.0%; intermediate and therapeutic doses administered in 79.4% of pancreatic cancer vs. 63.5% of other GI tumors (OR: 2.4, 95%CI: 1.2-4.5, p=0.0219). Doses had no co-relation with clinical setting (p>0.05), however, higher doses were preferred in metastatic disease (OR: 3.1, 95%CI: 1.2-7.5, p=0.0117). Average anticoagulation duration was 5.2±3.5 months; higher duration was observed in pancreatic tumors (5.5±3.7) and lower in colorectal, gastric and others (5.1±3.6, 4.9±2.6, 2.5±1.2, respectively). Two thrombotic events were reported (1.1%, 95%CI: 0.3-4.0%) in females with metastatic colorectal cancer. Three minor bleeding events were reported (1.7%, 95%CI: 0.6-4.9%) in pancreatic, colorectal and anal tumors. Oncologists are alerted about negative CAT influences in ambulatory patients with active cancer. GI tumors are usually metastatic and treated with HTA that contribute to high thrombotic burden. Potential drug-drug interactions drive anticoagulation, mainly with LMWHs. Effective anticoagulation doses are both efficacious and safe during the anti-neoplasmatic management of patients with active disease.

Prevalence of Abnormal Anal Cytology in Women with Abnormal Cervical Cytology.

Objective:The aim of this study was to evaluate the prevalence of abnormal anal cytology in women presenting with abnormal cervical cytology (intraepithelial lesion or cervical cancer) at the largest tertiary university hospital in Thailand. Methods:A cross-sectional prospective study design was used. Anal cytology was performed on 145 women with abnormal cervical cytology between June 2014-Octoble 2014. If abnormal anal cytology was detected, anoscopy was performed with biopsy in any suspicious area of precancerous change. Results:Prevalence of abnormal anal cytology was 5.5% (8 patients). Of 8 patients, six patients presented with low-grade squamous intraepithelial lesion, one patient with high-grade squamous intraepithelial lesion, and one with atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion. Abnormal anoscopic impression was found in 3 cases, as follow: The first case showed faint acetowhite lesion and anoscopic impression was low grade squamous intraepithelial lesion; the second case was reported as human papillomavirus (HPV) change by anoscopic impression; and the third case showed dense acetowhite lesion with multiple punctation and pathologic examination showed anal intraepithelial neoplasm III (AIN3). The last patient underwent wide local excision of AIN3 with split-thickness skin graft reconstruction. Final pathology confirmed AIN3 with free resection margin. Conclusion:Prevalence of abnormal anal cytology was 5.5% in patients with abnormal cervical cytology. The prevalence might be support anal cytology screening in this group of patients.

Association Between Pathological Complete Response and Tumor Location in Patients with Rectal Cancer After Neoadjuvant Chemoradiotherapy, a Prospective Cohort Study

Background: Colorectal cancers are the third common malignancies after lung and breast neoplasms. Some contributing factors for pathological complete response (pCR) to neoadjuvant therapy of rectal cancer have been defined. Despite various studies in this era, there are few studies on the location of tumors. Objectives: Regarding the high prevalence of colorectal cancer in Iran and the importance of neoadjuvant chemoradiation for survival and morbidity, this study was carried out to determine the association between pathologic complete response and tumor location in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods: In this prospective cohort, 100 cases with rectal adenocarcinoma from 2017 to 2019 were enrolled. Distance between anal verge and tumor was measured by clinical examination, colonoscopy, endo-sonography, and MRI. Tumors were defined as distal (less than 5 cm from the anal verge) and none distal (more than 5 cm from the anal verge). Another subdivision was inferior (0 - 4.99 cm), middle (5 - 9.99 cm), and superior (10 - 15 cm). The pathological response was compared across the groups. Results: In this study, the pCR was seen in 30%. In univariate analysis body mass index (BMI), grade, N-stage, and distance from anal verge were related to pCR. In cases with BMI over 25 kg/m2 and in tumors with low to medium grade N0/N1, and distance less than 5 cm from the anal verge (low lying tumors) the pCR to neoadjuvant treatment was higher. In multivariate analysis tumor grade, N stage, and distance from anal verge were still related to pCR. Conclusions: According to the obtained results in this study, there may be some association between rectal tumor location and pathologic complete response.

Lack of Conserved miRNA Deregulation in HPV-Induced Squamous Cell Carcinomas.

Squamous cell carcinomas (SCCs) in the anogenital and head and neck regions are associated with high-risk types of human papillomaviruses (HR-HPV). Deregulation of miRNA expression is an important contributor to carcinogenesis. This study aimed to pinpoint commonly and uniquely deregulated miRNAs in cervical, anal, vulvar, and tonsillar tumors of viral or non-viral etiology, searching for a common set of deregulated miRNAs linked to HPV-induced carcinogenesis. RNA was extracted from tumors and nonmalignant tissues from the same locations. The miRNA expression level was determined by next-generation sequencing. Differential expression of miRNAs was calculated, and the patterns of miRNA deregulation were compared between tumors. The total of deregulated miRNAs varied between tumors of different locations by two orders of magnitude, ranging from 1 to 282. The deregulated miRNA pool was largely tumor-specific. In tumors of the same location, a low proportion of miRNAs were exclusively deregulated and no deregulated miRNA was shared by all four types of HPV-positive tumors. The most significant overlap of deregulated miRNAs was found between tumors which differed in location and HPV status (HPV-positive cervical tumors vs. HPV-negative vulvar tumors). Our results imply that HPV infection does not elicit a conserved miRNA deregulation in SCCs.

Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes

BackgroundThis study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines.MethodsThe baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed.ResultsPET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region.ConclusionsThe results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.

Defining primary anal cancer tumour volume on FDG–PET – an initial assessment of semi–automated methods

Purpose Clinician inexperience, intra–observer and inter–observer variations in tumour definition may affect staging, radiotherapy target definition, and treatment outcomes, particularly in rare cancers. The purpose of this study was to assess the correlation between semi–automated methods of primary anal cancer (AC) definition and our current clinical standard of manual clinician definition using 18F–FDG–PET imaging and to provide recommendations for clinical use. Methods All patients referred for chemoradiotherapy for AC between 2012 and 2016 were prospectively enrolled, with all 18F–FDG–PET imaging acquired within one year of chemoradiotherapy collected. Three methods of primary AC definition were performed on all PET datasets. Manual definition by an experienced radiologist was considered the clinical standard for comparison of volume and coincidence (Dice coefficient) in our study. Semi–automated techniques assessed included a gradient–based SUV (SUV–gradient) method and a SUV threshold method with a range of thresholds relative to SUVmax (40 (T40), 50 (T50) and 60% (T60)). Results Ten patients were enrolled with 33 PET study sets available for analysis. While all methods created contours on pre– and post–treatment scans, manual definition of PET–avid disease was only necessary on 11 of the 33 study sets. SUV–gradient and T40 defined contours were not statistically different in volume to the clinical standard (p = 0.83 &amp; 0.72 respectively). The observed Dice coefficient relative to the manual clinician contours were 0.75 and 0.73 for the SUV–gradient and T40 methods respectively. Conclusions It is possible to define gross AC using SUV–based methods, with the SUV–gradient–based method followed by the T40 method most closely correlating with our current clinical standard. The SUV–gradient–based method studied is housed within a proprietary clinical system. A semi–automated approach that uses a vendor neutral T40 method and the clinician’s knowledge and skill appears optimal in defining AC. With this approach AC may be defined reliably to enhance efficiencies in radiotherapy and nuclear medicine processes, and to support clinicians in identifying and defining this rare disease. Trial registration ANZCTR, ACTRN12620000066987. Registered 28 January 2020–Retrospectively registered, https://www.anzctr.org.au/ACTRN12620000066987.aspx

MRI pelvimetry-based evaluation of surgical difficulty in laparoscopic total mesorectal excision after neoadjuvant chemoradiation for male rectal cancer

PurposeLaparoscopic total mesorectal excision (LaTME) is technically demanding in rectal cancer after neoadjuvant chemoradiotherapy (NCRT). This study aimed to predict the surgical difficulty of LaTME after NCRT based on pelvimetric parameters.MethodsThis study enrolled 147 patients who underwent LaTME after NCRT. The surgical difficulty was graded as high or low according to the operative time, estimated blood loss, conversion to open surgery, postoperative hospital stay, and postoperative complications. Pelvimetry parameters were collected based on preoperative MRI. A logistic regression analysis was performed to identify predictors of high surgical difficulty, and a nomogram was developed.ResultsTotally, 18 (12.2%) patients were graded as high surgical difficulty. High surgical difficulty was correlated with a shorter interspinous distance (P = 0.014), a small angle α and γ (P = 0.008, P = 0.008, respectively), and a larger mesorectal area and mesorectal fat area (P = 0.041, P = 0.046, respectively). Tumor distance from the anal verge (OR = 0.619, P = 0.024), tumor diameter (OR = 3.747, P = 0.004), interspinous distance (OR = 0.127, P = 0.007), and angle α (OR = 0.821, P = 0.039) were independent predictors of high surgical difficulty. A predictive nomogram was developed with a C-index of 0.867.ConclusionA shorter tumor distance from the anal verge, larger tumor diameter, shorter interspinous distance, and smaller angle α could help to predict high surgical difficulty of LaTME in male LARC patients after NCRT.

Implantation of rectosigmoid cancer in a preexisting anal fissure.

Colorectal cancer (CRC) rarely spreads by implantation. We report a case of implantation of rectosigmoid cancer in an anal fissure. A 70-year-old woman with a 15-year medical history of anal fissure was referred to our hospital with anal pain of 3-month duration. Colonoscopy revealed a rectosigmoid tumor and a 10-mm submucosal tumor at the anal verge. Biopsy of the rectosigmoid and anal tumors revealed that both were moderately differentiated adenocarcinomas, and abdominoperineal resection (APR) was performed. The anal adenocarcinoma was surrounded by squamous cell epithelium and mainly proliferated in the submucosal and muscular layers. The patient was diagnosed as having rectosigmoid cancer with implantation of cancer in a preexisting anal fissure. The patient remains well 43months post-surgery with no sign of recurrence. Implantation of CRC in anal fissure is a rare occurrence. Nevertheless, performing adequate anal examination of patients with CRC before surgery and during follow-up is necessary. Further, it is important to perform preoperative large bowel examination of patients with benign anal diseases to prevent implantation of CRC.