Laboratory procedures update on Hirschsprung disease.

OBJECTIVES: The detection of ganglion cells in rectal biopsies of infants or toddlers with severe constipation is routinely performed by pediatric pathologists in many institutions. Hirschsprung disease (HD) is defined by the lack of ganglion cells (aganglionosis). The early recognition and the prompt implementation of surgical procedures obviously protect infants affected with HD from potential life-threatening conditions, including enterocolitis and debilitating constipation. Image-based and non-image-based clinical techniques and some laboratory tests have been reevaluated along the years, but often fragmentarily. Immunohistochemical markers have been increasingly used in pathology laboratories to detect ganglion cells and nerve fibers. Recently, calretinin, a vitamin D-dependent calcium-binding protein with expression in ganglion cells and nerves, has been described as an adjunctive or primary diagnostic test in HD. The aim of the present study was to systematically summarize and update laboratory procedures targeting ganglion cells in rectal biopsies. METHODS: Procedures and tests have been reviewed and values of specificity and sensitivity have been calculated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Contrast enema has the lowest sensitivity and specificity of all of the 3-index investigations under the lens: contrast enema, anorectal manometry, and biopsy with histology. The latter procedure seems to have the highest sensitivity and specificity. Acetylcholinesterase staining on fresh-frozen material has been found to have slightly higher rates of sensitivity and specificity when compared with hematoxylin and eosin only. Calretinin staining may be supportive for the diagnosis, although some cases with false-positivity may be of some concern. CONCLUSIONS: Hematoxylin and eosin with or without acetylcholinesterase remains the criterion standard according to our PRISMA-based data. In our opinion, the number of false-positive results with potential overtreatment may limit the increasing advocacy for calretinin staining. Both the "primum non nocere" dictum and the "loss aversion heuristic" need to be satisfied harmoniously by preventing harm from unnecessary surgery.

Cancer Stem Cells and their Management in Cancer Therapy.

BACKGROUND: In the last decade, the proposed Cancer Stem Cell (CSC) hypothesis has steadily changed the way cancer treatment is approached. CSCs may be the source of the heterogeneous non-tumorigenic cell population included in a neoplasm. Intratumor and intertumoral heterogeneity is a well-known phenomenon that massively entangles the diagnosis and treatment of cancer. The literature seems to suggest that heterogeneity develops progressively within tumor-initiating stem cells. CSCs harbor genetic and/or epigenetic alterations that allow them to differentiate into multiple tumor cell types sequentially. OBJECTIVE: The CSC hypothesis, cellular therapy, and the most recent patents on CSCs were reviewed. METHODS: PubMed, Scopus, and Google Scholar were screened for this information. Also, an analysis of the most recent data targeting CSCs in pediatric cancer developed at two Canadian institutions is provided. The genes involved with the activation of CSCs and the drugs used to antagonize them are also highlighted. RESULTS: It is underlined that (1) CSCs possess stem cell-like properties, including the ability for self-renewal; (2) CSCs can start carcinogenesis and are responsible for tumor recurrence after treatment; (3) Although some limitations have been raised, which may oppose the CSC hypothesis, cancer progression and metastasis have been recognized to be caused by CSCs. CONCLUSION: The significant roles of cell therapy may include an auto-transplant with high-dose treatment, an improvement of the immune function, creation of chimeric antigen receptor T cells, and the recruitment of NK cell-based immunotherapy.

Traumatic neuroma of the anus after Milligan-Morgan hemorrhoidectomy.

There are several clinical settings of traumatic neuroma and a few may occur following surgical procedures. A 42-year-old man presented with anal pain five years after a Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. A 4×4×3 mm sized anal polyp was seen during a rectal examination at a follow-up five years after surgery. The patient complained of point tenderness, pruritus, and anal discomfort as well as fecal retention. An endoscopy revealed a rectal polyp. Remarkably, histopathological examination and immunohistochemistry of the excised polyp showed a polypoid traumatic neuroma of the rectal plexus. After the excision of the polyp, the patient's complaint resolved completely. Traumatic neuromas may be a cause of significant pain and tenderness in patients with anal surgery or repair of anal lacerations. Interestingly, this is the second case of anal traumatic neuroma since Dr. Marks' first case in 1956 and is a possible complication of Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. Similar complications of rectal surgery are reviewed.