Carcinoma of the neck showing thymic-like elements (CASTLE): report of a case and review of the literature.

Carcinoma showing thymic-like elements (CASTLE) is a rare tumor affecting thyroid and neck soft tissues, which has to be distinguished from squamous cell and anaplastic thyroid carcinoma, because it has a better prognosis. We report a new case of CASTLE which occurred in a patient submitted to total thyroidectomy with central neck dissection. The tumor stained positively for CD5, which seems to be the most useful marker in the differential diagnosis. By the analysis of the 18 cases reported in literature, total thyroidectomy with selective modified neck dissection should be the treatment of choice and radiotherapy should be considered for patients with positive nodal status.

Preoperative IL-2 immunotherapy enhances tumor infiltrating lymphocytes (TILs) in gastric cancer patients.

BACKGROUND/AIMS: Tumor infiltrating lymphocytes (TILs), recognized as a tumor-host reaction, have been linked to prognosis in various tumors, with a clear positive correlation between the density of the lymphoid infiltrate at the advancing margin of the tumor and the prognosis of the patients. TILs are somewhat activated by tumor associated antigens and by IL-2 endogenous release. The aim of this study is to verify if subcutaneously administered IL-2 is able to enhance TILs in gastric cancer patients and is able to influence the prognosis of the patients. METHODOLOGY: We enrolled 39 consecutive patients with gastric adenocarcinoma. Patients were randomized to be treated with surgery alone (control group, 20 patients) or with surgery plus preoperative IL-2 (Interleukin-2) administration (treated group, 19 patients). Total lymphocytes, CD4 and CD4/CD8 were evaluated pre- and postoperatively. Peritumoral stromal reaction, neutrophils, lymphocytes and eosinophils infiltration in tumor histology were evaluated as well as survival curves and compared between the groups. RESULTS: IL-2 treatment was safe and well tolerated, and in the IL-2 treated group a significant increase over the baseline pretreatment values of the total lymphocyte, CD4 and CD4/CD8 on both the 14th and 50th postoperative days was observed (p < 0.05). Peritumoral stromal reaction, neutrophils and eosinophils infiltration did not shown any statistical difference between the two groups. Otherwise we observed a statistically significant difference in the peri- and intratumoral lymphocytes infiltration between IL-2 treated and control patients (p = 0.000026). Median overall and disease-free survivals were longer, even if not significantly, in the IL-2 group than in the control arm (p = 0.089 and p = 0.09 respectively). CONCLUSIONS: Our data shows that IL-2 seems to be able to induce substantial changes in the inflammatory infiltration of the neoplasm, improving the host activity toward the tumor and enhancing the TILs phenomenon in gastric cancer patients. This feature seems to improve the prognosis of the patients.

Phase-II randomized study of preoperative IL-2 administration in radically operable gastric cancer patients.

BACKGROUND/AIMS: Surgery has appeared to induce lymphocytopenia and this decrease in host defenses during postoperative period could promote both the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. The aim of this study is to evaluate if the preoperative subcutaneous injection of IL-2 (interleukin-2) may be able to abrogate surgery-induced immunosuppression in radically operable gastric cancer and to assess its toxicity. METHODOLOGY: This phase II study included 39 consecutive patients with histologically proven gastric adenocarcinoma (M/F 26/13; mean age 68; range 48-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (20 patients) or surgery plus preoperative treatment with recombinant human IL-2 (19 patients). IL-2 was administered subcutaneously, at a dose of 9,000,000 IU, for three consecutive days, followed by surgery within 36 hours from IL-2 withdrawal. We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. Among the 22 patients evaluated in the control group 13 had a decreased of CD4 under 500 cells/mm3 (65%). Instead in the IL-2 group a significant increase was observed over the control group values of total lymphocytes and CD4 cells (14th ly total and CD4: IL-2 vs. control p<0.05). Moreover in this group only 3 patients had CD4 under 500 cells/mm3 (15%). This difference in CD4 count, is significant at the 50th postoperative day too (p=0.006). No anesthesiologic or surgical complication was seen in IL-2 treated group, with low grade of toxicity (WHO grade:1): the main effect was fever (14/19) easily manageable, with no cardiovascular complications. Furthermore, IL-2 group showed lower postoperative complications (p<0.05) and higher lymphocyte/eosinophil infiltration into the tumor (p<0.002). CONCLUSIONS: This phase II study would suggest that a preoperative immunotherapy with IL-2 is a well tolerated treatment able to prevent surgery induced lymphocytopenia. IL-2 seems to neutralize the immunosuppression induced by operation and so to stimulate the host reaction against tumor tissue (lymphocytes/eosinophils infiltration). Next randomized clinical trials could investigate the prognostic impact of IL-2 on the clinical course.

Thrombosis of the splenoportal axis after splenectomy.

BACKGROUND AND AIMS: Thrombosis of the portal system is a potentially life-threatening complication after splenectomy. The reported incidence is low (approximately or = 1%), however may be underestimated due to difficult in making the diagnosis. The factors associated with its development and the clinical outcome are poorly characterized. The aim of this study was to assess the incidence, risk factors, treatment, and outcome in series of consecutive cases. MATERIALS AND METHODS: All patients who had undergone a splenectomy (both open and laparoscopic) between January 1997 and December 2004 at the Department of Surgery of University of Milan Bicocca were retrospectively reviewed. Twelve cases of thrombosis (7.6%) among 158 splenectomies were identified. No significant differences were noted in age, gender, and surgical approach between patients who developed thrombosis and those who did not. Indication for splenectomy in patients with thrombosis were myeloproliferative disorders (n=5), hemolytic disease (n=4), and lymphoproliferative disorder (n=3). All patients had splenomegaly (mean 1.380 kg, range 0.400-3.120 kg). RESULTS: Among patients with myeloproliferative disorders, five (33%) developed the complication, compared with 4 of 35 (11.5%) with hemolytic disease. Patients with both splenic weight >2.500 kg and myeloproliferative disorders had 80% incidence of portal thrombosis. Preoperative prophylactic anticoagulant therapy with low molecular weight heparin was administered in each case. All these patients had fever, abdominal pain, or leukocytosis. All diagnoses were made by contrast-enhanced computed tomography (CT) scan and ecocolordoppler ultrasonography, and anticoagulation therapy was initiated immediately. Treatment within 15 days after splenectomy was successful in all patients, while delayed treatment was ineffective. CONCLUSIONS: Portal thrombosis should be suspected in patients with fever or abdominal pain after splenectomy. Patients with myeloproliferative disorders and hemolytic diseases are at higher risk, as well as patients with marked splenomegaly. A high index of suspicion, early diagnosis, and prompt anticoagulation therapy are the keys to a successful outcome.