Adjuvant therapy in primary GIST: state-of-the-art.

BACKGROUND: The management of primary gastrointestinal stromal tumours (GISTs) has evolved with the introduction of adjuvant therapy. Recently reported results of the SSG XVIII/AIO trial by the Scandinavian Sarcoma Group (SSG) and the German Working Group on Medical Oncology (AIO) represent a significant change in the evidence for adjuvant therapy duration. The objectives of this European Expert Panel meeting were to describe the optimal management and best practice for the systemic adjuvant treatment of patients with primary GISTs. MATERIALS AND METHODS: A panel of medical oncology experts from European sarcoma research groups were invited to a 1-day workshop. Several questions and discussion points were selected by the organising committee prior to the conference. The experts reviewed the current literature of all clinical trials available on adjuvant therapy for primary GISTs, considered the quality evidence and formulated recommendations for each discussion point. RESULTS: Clinical issues were identified and provisional clinical opinions were formulated for adjuvant treatment patient selection, imatinib dose, duration and patient recall, mutational analysis and follow-up of primary GIST patients. Adjuvant imatinib 400 mg/day for 3 years duration is a standard treatment in all patients with significant risk of recurrence following resection of primary GISTs. Patient selection for adjuvant therapy should be based on any of the three commonly used patient risk stratification schemes. R1 surgery (versus R0) alone is not an indication for adjuvant imatinib in low-risk GIST. Recall and imatinib restart could be proposed in patients who discontinued 1-year adjuvant imatinib within the previous 3 months and may be considered on a case-by-case basis in patients who discontinued within the previous year. Mutational analysis is recommended in all cases of GISTs using centralised laboratories with good quality control. Treatment is not recommended in an imatinib-insensitive D842V-mutated GIST. During adjuvant treatment, patients are recommended to be clinically assessed at 1- to 3-month intervals. Upon discontinuation, computed tomography scan (CT) scans are recommended every 3 to 4 months for 2 years when the risk of relapse is highest, followed by every 6 months until year 5 and annually until year 10 after treatment discontinuation. CONCLUSIONS: Key points in systemic adjuvant treatment and clinical management of primary GISTs as well as open questions were identified during this European Expert Panel meeting on GIST management.

Anal canal duplication: a retrospective analysis of 12 cases from two European pediatric surgical departments.

Anal canal duplication (ACD) represents an extremely rare intestinal congenital anomaly of unknown origin. Usually evidenced within 2 years of age, nearly 45% of reported cases present associated malformations such as presacral mass, anorectal malformation (ARM) and genitourinary anomalies. The confirmative diagnosis is histopathological, with evidence of an anal mucosal lining (squamous +/- transitional epithelium), surrounded from a smooth muscle coat and anal glands. We review a conjoined experience from two European pediatric surgical departments. From 1970 to 2005, 12 patients were observed, seven in Pescara, Italy (1997-2005), five in Barcelona, Spain (1970-2004) - mean age at diagnosis 17.8 months, range 0-60; M:F = 1:11. Clinical presentation, diagnostic-surgical approach, and complications were reviewed. According to clinical presentation, patients could be divided in three age groups: asymptomatic (mean age 4.8 months, six patients - one with an associated complex genitourinary malformation, one with a presacral mature teratoma, one with ACD evidenced hysthologically on a retroanal mass removed during the correction of an ARM), mildly symptomatic - constipation, mucous discharge (mean age 29.2 months, four patients - one with associated presacral ependymoma and intestinal neuronal dysplasia type B, one with presacral mass) and complicated - perineal abscess, recurrent fistula (mean age 34 months, two patients). In 11 cases a perianal orifice was evident (ten posteriorly located). The pelvic-MRI was the preferred diagnostic tool in Pescara (5/7, with presacral mass in two patients), fistulography in Barcelona (5/5), where one presacral mass was discovered intraoperatively. Eleven patients underwent surgical removal of the ACD (five perineal approach, five posterior sagittal approach, and one PSARP). Histopathological findings confirmed the diagnosis in operated cases (11). The parents of the male patient denied the consent to surgical treatment. The only major post-operative complication was a sphincteric insufficiency (one case), surgically treated. When facing a perianal orifice, attention should be paid to ACD, particularly in female patients with coexistent genitourinary or intestinal malformations. Pelvic US and MRI are the gold standard to evidence the not rarely associated presacral mass. Surgical early removal (mucosectomy or perineal/posterior sagittal approach, depending on length of ACD and associated presacral mass) is warranted, also in asymptomatic patients, because of the risk of inflammatory complications and cancer (the latter reported in literature in adults).