Mario Antonello Rosito

Sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal: early experience.

PURPOSE This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal. METHODS Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3). RESULTS Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal. CONCLUSIONS The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.

Sentinel Lymph Node Procedure in Patients With Epidermoid Carcinoma of the Anal Canal

AbstractPURPOSE: This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal. METHODS: Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3). RESULTS: Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal. CONCLUSIONS: The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.

Massive zosteriform cutaneous metastasis from rectal carcinoma.

Abstract.A 44-year-old man presented with a large and rapidly growing skin lesion approximately six months after resection of a rectal carcinoma. The lesion measured 40 cm in size, extended from the suprapubic area to the proximal half of the left groin, and showed a particular zosteriform aspect. Biopsy confirmed a metastatic skin adenocarcinoma. Cutaneous metastases from rectal cancer are very uncommon. Their gross appearance is not distinctive, although the skin tumors are usually solid, small (less than 5 cm) and painless nodules or papules. Early biopsies for suspicious skin lesions are needed in patients with a history of colorectal cancer.

Study of killer immunoglobulin-like receptor genes and human leukocyte antigens class I ligands in a Caucasian Brazilian population with Crohn's disease and ulcerative colitis

Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel, of unknown origin. Exposure to specific environmental factors by genetically susceptible individuals, leading to an inadequate response of the immune system, is one of the potential explanations for the occurrence of these diseases. Natural killer cells are part of the innate immune system recognizing class I HLA (human leukocyte antigen) molecules on target cells through their membrane receptors. The main receptors of the natural killer cells are the killer immunoglobulinlike receptors (KIRs). Our study aimed to evaluate the association between the KIR genes in patients with inflammatory bowel diseases and healthy controls. We typed 15 KIR genes and HLA class I ligands in 248 unrelated Brazilian Caucasians, of which 111 had UC and 137 had CD, and 250 healthy controls by polymerase chain reaction using sequence-specific oligonucleotides and sequence-specific primers. We found an increase in KIR2DL2 in controls (inflammatory bowel disease [IBD]: p < 0.001; UC: p = 0.01; CD: p = not significant [NS]). The genotype 2DL2+/HLA-C lys(80)+ was also more common in controls (IBD: p = 0.005; UC: p = 0.01; CD: p = NS); as well as 2DL1+/HLA-C Asn(80)+ (IBD: p = 0.026; UC: p = NS;CD: p = NS). The imbalance between activating and inhibitory KIR and HLA ligands may explain, at least in part, the pathogenesis of these inflammatory bowel diseases.

Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic.

AIM To determine the prevalence of a family history suggestive of Lynch syndrome (LS) among patients with colorectal cancer (CRC) followed in a coloproctology outpatient clinic in Southern Brazil. METHODS A consecutive sample of patients with CRC were interviewed regarding personal and family histories of cancer. Clinical data and pathology features of the tumor were obtained from chart review. RESULTS Of the 212 CRC patients recruited, 61 (29%) reported a family history of CRC, 45 (21.2%) were diagnosed under age 50 years and 11 (5.2%) had more than one primary CRC. Family histories consistent with Amsterdam and revised Bethesda criteria for LS were identified in 22 (10.4%) and 100 (47.2%) patients, respectively. Twenty percent of the colorectal tumors had features of the high microsatellite instability phenotype, which was associated with younger age at CRC diagnosis and with Bethesda criteria (P < 0.001). Only 5.3% of the patients above age 50 years had been previously submitted for CRC screening and only 4% of patients with suspected LS were referred for genetic risk assessment. CONCLUSION A significant proportion of patients with CRC were at high risk for LS. Education and training of health care professionals are essential to ensure proper management.

FIBRIN GLUE IN THE MANAGEMENT OF COMPLEX ANAL FISTULA

CONTEXT Management of complex anal fistulas is associated with the risk of sphincter injury and fecal incontinence. In recent years, fibrin glue has emerged as an alternative sphincter-preserving treatment for anal fistulas. To date, however, there is no consensus about the efficacy of the method. OBJECTIVE To specifically evaluate the fibrin glue injection in the management of complex cryptoglandular anal fistulas. METHODS We studied a series of patients with complex anal fistulas treated with fibrin glue between January 2005 and January 2007. Only patients with fistulas of cryptoglandular origin were analyzed. Patients with fistulas related to Crohns disease, HIV or previous surgery were excluded from the study. Under spinal anesthesia, the fistulas were curetted and injected with fibrin glue. After treatment, patients were followed-up for 12 months. RESULTS Thirty-two patients were enrolled in the study. Two patients were lost to follow-up and were excluded. Out of the remaining 30 patients, only three healed successfully (10%). Among the 27 patients who failed to heal, 9 (33.3%) were diagnosed within the first postoperative month. In 13 patients (48.1%) the failure of treatment occurred in the period between 1 and 3 months, in 3 patients (11.1%) between 3 and 6 months, and in 2 patients (7.4%) between 6 and 9 months after surgery. No treatment-related complications were observed. CONCLUSIONS In this series, fibrin glue treatment for complex cryptoglandular anal fistulas achieved a very low healing rate. Our results do not support the use of fibrin glue as a first-line treatment for patients with this type of fistula.

Metastatic renal cell carcinoma involving the rectum.

AbstractBackground and aims. Metastatic spread of a distant tumor to the rectum is extremely rare. To our knowledge, there have been no published reports of hematogenic metastasis from a renal cell carcinoma to the rectum. Patients and methods. A patient with a renal cell carcinoma was initially treated by a radical right nephrectomy. Results. Nine months after the surgery he started to have multiple episodes of hematochezia. Colonoscopy showed a nodular lesion located in the distal rectum, and biopsy revealed an undifferentiated carcinoma. The patient then underwent abdominoperineal resection of the rectum, and histological examination showed metastatic renal clear cell carcinoma. Conclusion. This case represents an exceedingly rare condition, which has never been reported before.

Effects of the gastrin-releasing peptide antagonist RC-3095 in a rat model of ulcerative colitis.

BackgroundRC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified as a candidate compound for the treatment of tumor necrosis factor (TNF)-dependent chronic inflammatory conditions.AimThe aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis.MethodsNinety Wistar rats were included in the study. Colitis was induced by a single intracolonic application of acetic acid. Rats were divided into three groups of treatment: subcutaneous RC-3095, intracolonic mesalazine, and subcutaneous dexamethasone. Additionally, there was a fourth group of animals submitted to induction of colitis without receiving any form of treatment, and a fifth group in which no colitis was induced. Seventy-two hours after instillation of acetic acid, the animals were killed and the following parameters were assessed: morphological score of damage, histological score of colonic inflammation, and immunohistochemical expression of TNF-α and interleukin (IL)-1β.ResultsRC-3095 was the only treatment to significantly reduce macroscopic and microscopic scores of inflammation as compared with the animals from the non-treated colitis group. RC-3095 also significantly reduced the colonic expression of TNF-α, but not the expression of IL-1β.ConclusionsRC-3095 reduced the colitis severity in a well-established experimental model of IBD. The anti-inflammatory activity of this compound was associated with a reduction in the colonic expression of TNF-α. These results suggest that interference with GRP pathway might represent a potential new strategy for the treatment of ulcerative colitis that deserves further investigational studies.

Colonoscopia com magnificação de imagem no diagnóstico de carcinoma colorretal invasivo da submucosa na polipose adenomatosa familiar

O desenvolvimento da colonoscopia com magnificacao de imagem possibilitou o estudo detalhado da mucosa colonica e o diagnostico diferencial entre lesoes neoplasicas e nao-neoplasicas, a partir da observacao dos pit patterns. Os resultados sao comparaveis a estereomicroscopia, sendo possivel, assim, presumir o diagnostico histologico. Foi realizada colonoscopia com magnificacao de imagem em paciente portadora de polipose adenomatosa familiar, demonstrando-se com este metodo, a diversidade de lesoes polipoides benignas e as apresentacoes morfologicas do câncer colorretal precoce. Nesta paciente, a avaliacao por magnificacao (videocolonoscopio FUJINON 410 - CM ¾ 40X), combinada a cromoscopia com indigo carmine 0,4%, demonstrou ampla variedade de lesoes distribuidas por todo o colon: lesao de espalhamento lateral no ceco com padrao IIIL + IV, polipos subpediculados e sesseis distribuidos pelo colon com padrao tipo IIIL, polipo subpediculado no colon transverso com diâmetro aproximado de 2,0 cm e padrao IV + V, lesoes plano-elevadas tipo IIIL e no colon sigmoide lesao IIa + IIc, com padrao V de Kudo. A avaliacao dos pit patterns de lesoes no colon transverso e sigmoide permitiu o diagnostico endoscopico de lesao com invasao de submucosa.The development of colonoscopy with image magnification has enable to study the colonic mucosa in detail and to do differential diagnosis between neoplastic and non-neoplastic lesions from the observation of pit patterns. The results are comparable to stereomicroscopy being possible to predict the histologic diagnosis. In a patient with familial adenomatous polyposis magnifying colonoscopy was performed and this method demonstrated a wide variation of benign polypoid lesions and the morphological features of early colorectal cancer. In this patient, the evaluation by image magnification, together with indigo carmin 0.4% chromoscopy, showed a wide variety of lesions in the colon and rectum: laterally spreading tumor in the cecum, with IIIL + IV pits, subpediculate polyp in the transverse colon with approximately 2.0 cm diameter and IV + V pits, flat elevated lesions IIIL type, and in the sigmoid colon IIa + IIc lesion with V type of Kudos classification were observed. The evaluation of pit patterns of the lesions in the transverse and sigmoid colon has enable to do the endoscopic diagnosis of the lesion with submucosal invasion.The development of colonoscopy with image magnification has enable to study the colonic mucosa in detail and to do differential diagnosis between neoplastic and non-neoplastic lesions from the observation of pit patterns. The results are comparable to stereomicroscopy being possible to predict the histologic diagnosis. In a patient with familial adenomatous polyposis magnifying colonoscopy was performed and this method demonstrated a wide variaton of benign polypoid lesions and the morphological features of early colorectal cancer. In this patient, the evaluation by image magnification, together with indigo carmin 0,4% chromoscopy, showed a wide variety of lesions in the colon and rectum: laterally spreading tumor in the cecum, with IIIL + IV pits, subpediculate polyp in the transverse colon with approximately 2,0 cm diameter and IV + V pits, flat elevated lesions IIIL type, and in the sigmoid colon IIa + IIc lesion with V type of Kudos classification were observed. The evaluation of pit patterns of the lesions in the transverse and sigmoid colon has enable to do the endoscopic diagnosis of the lesion with submucosal invasion.

Long-term survival data on sentinel lymph node biopsy in anorectal melanoma

Sentinel lymph node (SLN) biopsy is currently the method of choice to assess the nodal status of patients with cutaneous melanoma. It has largely replaced elective lymph node dissection, sparing patients with negative SLN the morbidity associated with a complete regional lymphadenectomy. However, experience with the SLN procedure in anal melanoma has been limited to a few reported cases, probably due to the rarity of this tumor. Anorectal melanoma (AM) accounts for 1% of all anorectal malignancies. Most patients are diagnosed with advanced disease and have poor 5-year survival (0–22%). Although surgery is the mainstay of treatment, there appears to be no difference in survival whether wide local excision (LE) or abdominoperineal resection is performed. Locoregional metastases are frequent and may involve both inguinal and pelvic lymph nodes [1]. In this letter, we report a case of AM that had an unexpectedly favorable clinical evolution. Our patient was an 89-year-old diabetic woman presenting with an anal lesion that she first noticed 8 months earlier. It was a non-pigmented nodule, 3 cm in diameter, located at the dentate line. Inguinal palpation was unremarkable. Biopsy of the lesion showed an undifferentiated tumor, but the immunohistochemical analysis was positive for S-100 protein and HMB-45, thus establishing the diagnosis of AM. Staging workup did not detect metastases. Considering the general condition of the patient, treatment by wide local excision of the tumor along with SLN biopsy was proposed. Twelve hours before surgery, Dextran 500 labeled with Technetium-99 m was injected into the parenchyma around the primary tumor. Subsequently, lymphoscintigraphy demonstrated a SLN (hot spot) in the right groin (Fig. 1). On the following day, patent blue dye was injected at the same sites around the tumor. The inguinal area was scanned with a gamma probe, and a 3-cm incision was made over the hot spot. During inguinal dissection, the blue color of the SLN served as a guide to its location. After removal of the SLN, excision of the AM was performed. Histopathology and immunohistochemistry of the surgical specimen confirmed AM with tumor-free resection margins. The SLN was diagnosed as positive for metastatic melanoma. The patient refused any additional treatment but remained free of disease after 52 months of follow-up. Although the SLN procedure has been successfully tested in other anal tumors, the investigation into the SLN in AM is currently limited to 6 cases [1–4]. Long-term survival was not documented in any of them. In our patient, we used the same SLN procedure we had previously investigated in cases of epidermoid carcinoma of the anal canal and rectal adenocarcinomas invading the dentate line [5, 6]. Our technique, which consisted of a combination of blue dye and radio-colloid, was effective in sampling a SLN from the left inguinal area. Moreover, it allowed the detection of metastatic deposits within the SLN, which D. C. Damin (&) M. A. Rosito Division of Coloproctology, Hospital de Clinicas de Porto Alegre (Sala 600) and Department of Surgery, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035 903 Porto Alegre, RS, Brazil e-mail: damin@terra.com.br