Prognostic markers in rectal neuroendocrine tumors

M1 - 87 s. + liitteet Helsingin yliopistoNeuroendocrine tumors of the rectum were regarded as benign, when Oberndorfer originally described the entity in 1907. Later, he acknowledged that some neuroendocrine tumors (or carcinoids, the term at that time) behave in a more aggressive manner, and a few of them even had the potential to metastasize with poor outcome. In the novel World Health Organization (WHO) classification launched in 2010, all neuroendocrine tumors of the gastrointestinal (GI) tract are malignant. In this classification, tumors of every part of the GI tract are graded uniformly according to proliferation index and mitotic frequency, whereas the TNM-classification (tumor, node, metastasis) is specific for each site. Around 10% of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) occur in the rectum. The tumor series comprised 73 rectal NETs, with the main objective being to study the prognostic value of the WHO 2010 classification in rectal NETs: additionally, as the WHO classification has been used for a rather short time, tumor markers were tested to find a good, reliable prognostic tool. The WHO 2010 had excellent prognostic significance; none of the G1- NETs (grade 1) metastasized, whereas G2-NETs were often disseminated, some of them at initial presentation. Metastatic NETs have a poor prognosis. Cell-cycle antigen cyclin A also correlated with prognosis, and G2-NETs with high cyclin A expression were all metastatic. Transcription factor prospero homeobox 1 (PROX1) was immunohistochemically positive in a significant proportion of rectal NETs, and showed a correlation with metastatic potential and survival. It was also possible to conclude that the novel stem cell-associated factor HES77 (human embryonic stem cell factor 77) correlated well with rectal NETs metastatic potential and prognosis. These results support the validity of the WHO 2010 classification in rectal NETs. In view of this study, for patients with a rectal G1-NET, one follow-up endoscopy to exclude local recurrence might suffice. Intensive follow-up does not seem indicated, as metastatic potential is very low. As to G2-NETs, a thorough work-up is recommended, since most of these tumors disseminate eventually, some after several years, and a standard 5-year follow-up may not suffice. PROX1-positivity suggests that colorectal adenocarcinoma and rectal NET may, to some extent, share the same pathway in oncogenesis, which could lead to future therapeutic applications

Sentinel node tumor burden in prediction of prognosis in melanoma patients

Recent data have demonstrated no survival benefit to immediate completion lymph node dissection (CLND) for positive sentinel node (SN) disease in melanoma. It is important to identify parameters in positive SNs, which predict prognosis in melanoma patients. These might provide prognostic value in staging systems and risk models by guiding high-risk patients' adjuvant therapy in clinical practice. In this retrospective study of university hospital melanoma database we analyzed tumor burden and prognosis in patients with positive SNs. Patients were stratified by the diameter of tumor deposit, distribution of metastatic focus in SN, ulceration and number of metastatic SNs. These were incorporated in Cox proportional hazard regression models. Predictive ability was assessed using Akaike information criterion and Harrell's concordance index. A total of 110 patients had positive SN and 104 underwent CLND. Twenty-two (21%) patients had non-SN metastatic disease on CLND. The 5-year melanoma specific survival for CLND-negative patients was 5.00 years (IQR 3.23-5.00, range 0.72-5.00) compared to 3.69 (IQR 2.28-4.72, range 1.01-5.00) years in CLND-positive patients (HR 2.82 (95% CI 1.17-6.76, p = 0.020).The models incorporating distribution of metastatic focus and the largest tumor deposit in SN had highest predictive ability. According to Cox proportional hazard regression models, information criterions and c-index, the diameter of tumor deposit > 4 mm with multifocal location in SN despite of number of metastatic SN were the most important parameters. According to the diameter of tumor deposit and distribution of metastatic focus in SN, adequate stratification of positive SN patients was possible and risk classes for patients were identified.Peer reviewe

Characteristics and Trends of Cutaneous Squamous Cell Carcinoma in a Patient Cohort in Finland 2006-2015

The incidence of cutaneous squamous cell carcinoma is increasing worldwide. In most epidemiological studies, only the first case of cutaneous squamous cell carcinoma is registered, underestimating the burden of the disease. To determine the frequency and detailed characteristics of cutaneous squamous cell carcinoma in a Finnish patient cohort, we performed a retrospective 10-year study taking into account multiple tumours in one patient. On the pathology database search and medical record review we identified 774 patients with a total of 1,131 cutaneous squamous cell carcinomas. The crude incidence increased from 18.6/100,000 persons in 2006 to 28.1 in 2015. The location of tumours differed between men and women: the greatest difference concerned cutaneous squamous cell carcinoma of the ear, with 93% of cases occurring in men. One fourth (24%) of patients had more than one tumour. A small shift from poorly to well-differentiated tumours was seen. In conclusion, the incidence of cutaneous squamous cell carcinoma increased, with many patients presenting with multiple tumours.Peer reviewe

Premalignant lesions, basal cell carcinoma and melanoma in patients with cutaneous squamous cell carcinoma

The incidence of keratinocyte carcinomas is increasing worldwide and currently there is no standardised strategy for the follow-up of patients with multiple tumours. The objective of this study was to assess the prevalence of premalignant lesions, i.e., actinic keratosis and Bowen's disease, as well as basal cell carcinoma (BCC) and cutaneous melanoma (CM) among patients with cutaneous squamous cell carcinoma (cSCC). Pathology database search was performed to identify all cSCC patients diagnosed in the Pirkanmaa region of Finland in 2006-2015. Details of the patients and tumours were obtained through medical record review. The cohort consisted of 774 patients with 1131 cSCC tumours. Overall 559 patients (72%) had premalignant lesions. A total of 316 patients (41%) had BCC and 52% of these (n = 164) had more than one BCC tumour. 50 patients (6%) had CM. Overall 180 cSCC patients (23%) had no premalignant changes, BCC or CM. The median age of these patients was 6 years less than that of the patients with premalignant lesions (p <0.001) or BCC (p <0.001). The invasion depth of the tumours was deeper in the patients with only cSCC (median 3 mm, interquartile range 2-6) than in those with premalignant lesions or BCC (median 2 mm, interquartile range 1-3),p <0.001. CSCC patients have a high risk of developing multiple skin cancers and need long-term follow-up.Peer reviewe

Recurrent and Metastatic Cutaneous Squamous Cell Carcinomas in a Cohort of 774 Patients in Finland

Dermato-Venereologica Recognising patients with high risk cutaneous squamous cell carcinomas is essential in planning effective monitoring. The aim of this study was to determine the rate of local recurrences and metastases of cutaneous squamous cell carcinomas in a previously defined patient cohort in Finland. Pathology database search was performed to identify cutaneous squamous cell carcinoma patients and their medical records were reviewed. The cohort consisted of 774 patients with 1,131 cutaneous squamous cell carcinoma tumours. Overall, 4.2% (48/1,131) of the tumours were metastatic and 2.2% (25/1,131) had a local recurrence. Three of the metastatic tumours and 8 of the recurrent tumours had an invasion depth ofPeer reviewe

Gluten Challenge Induces Skin and Small Bowel Relapse in Long-Term Gluten-Free Diet-Treated Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH.Peer reviewe

Premalignant lesions, basal cell carcinoma and melanoma in patients with cutaneous squamous cell carcinoma

The incidence of keratinocyte carcinomas is increasing worldwide and currently there is no standardised strategy for the follow-up of patients with multiple tumours. The objective of this study was to assess the prevalence of premalignant lesions, i.e., actinic keratosis and Bowen's disease, as well as basal cell carcinoma (BCC) and cutaneous melanoma (CM) among patients with cutaneous squamous cell carcinoma (cSCC). Pathology database search was performed to identify all cSCC patients diagnosed in the Pirkanmaa region of Finland in 2006-2015. Details of the patients and tumours were obtained through medical record review. The cohort consisted of 774 patients with 1131 cSCC tumours. Overall 559 patients (72%) had premalignant lesions. A total of 316 patients (41%) had BCC and 52% of these (n = 164) had more than one BCC tumour. 50 patients (6%) had CM. Overall 180 cSCC patients (23%) had no premalignant changes, BCC or CM. The median age of these patients was 6 years less than that of the patients with premalignant lesions (p <0.001) or BCC (p <0.001). The invasion depth of the tumours was deeper in the patients with only cSCC (median 3 mm, interquartile range 2-6) than in those with premalignant lesions or BCC (median 2 mm, interquartile range 1-3),p <0.001. CSCC patients have a high risk of developing multiple skin cancers and need long-term follow-up.Peer reviewe

Anaemia in Dermatitis Herpetiformis : Prevalence and Associated Factors at Diagnosis and One-year Follow-up

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment.publishedVersionPeer reviewe