Splenectomy Tonsillectomy and Appendectomy - Complications and Cancer Occurrence

The removal of secondary lymphoid tissue is not innocuous. Infectious complications in procedures such as total splenectomies are frequent and may be fatal. Sequelae may be thromboembolic. Immune alterations are expected after such procedures. The most controversial consequence, one that is linked with immune changes, is the development of malignant tumors. Regarding post-splenectomy malignancies, there appears to be marked discrepancies between the increased occurrence of tumors in humans and the protective effects seen in experimental animals. It is recommended, that surgeons strive to preserve as much lymphoid tissue as possible. Benharroch D1*, Nalbandyan K1, Kraus M2, Osyntsov A3 and Ariad S4 1Department of Pathology, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel 2Department of ENT, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel 3Department of Surgery B, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel 4Department of Oncology, Soroka University Medical Center and the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel Benharroch D, et al. Clinics in Oncology Endometrial Cancer Remedy Publications LLC., | http://clinicsinoncology.com/ 2016 | Volume 1 | Article 1037 2 in Hodgkin lymphoma are independently associated with breast cancer occurrence [7]. In contrast, experimental splenectomy in mammary tumorbearing rats leads to a markedly reduced tumor rate (45% in splenectomized rats, compared with 70% in control rats). In tumorcarrying rats, splenectomy causes a significant increase in circulating NK cells. In these rats, the resected spleens contain fewer CD4+ and CD8+ lymphocytes and significantly more CD4and CD8lymphocytes [8]. A study in mice has further supported the role of splenectomy in inhibiting tumor growth and metastatic spread. The effects of splenectomy may be mediated by the depletion of myeloid suppressor cells [9]. Thus, splenectomy in a clinical context appears to produce a different and permissive effect in promoting cancer, whereas in experimental animals it may suppress tumor growth. Notably, in the clinical setting, abnormal natural killer lymphocytes is follows splenectomy and may be associated with recurrent infections, polyclonal B-cell proliferation and relapsing neutropenia [10]. In mice, however, resection of 70% of the spleen appears to be optimal because this amount is accompanied by a marked decrease in mononuclear cells and prevents the excessive leukocytes is observed in a complete resection [11].The immune response that occurs after a stroke often delays neuronal death. In splenectomized rats this neuroprotective effect is lost as it is mediated by IFNγ [12]. In an attempt to further clarify the multiple functions of the spleen, rats with cardiac allografts have been splenectomized. Splenectomy significantly extends the survival of the heart allograft by delaying inflammatory infiltrates and subsequent myocardial rejection. Splenectomy also increases the lymphocytic apoptotic rate. In another study, splenectomy has been found to exert its effects by inducing immunological tolerance [13]. Myocardial ischemiareperfusion injury shows that myocardial inflammation is localized in the re-perfused area. Splenectomy protects the myocardium by limiting the infiltration of phagocytic monocytes [14]. In a cohort of 8,149 splenectomized veterans who were initially tumor-free, solid tumors (buccal, hepatic, colonic, esophageal, pancreatic, prostatic and pulmonary) have been found to be more frequent by a ratio of 1.3-1.9, compared with non-splenectomized individuals. In the splenectomized veterans, hematological malignancies were more frequent by a ratio of 1.8-6.0 compared with non-splenectomized individuals. Death from any cancer in this group of patients was from 1.3 to 4.7 times more frequent than in the non-splenectomized group [15]. The findings of this study, although supported by only few epidemiological reports, may be consistent with the experimental results of post-splenectomy cancer progression in mice and rats as described many years ago [16,17]. These discrepancies in the epidemiological reports may be due to the inclusion of patients who had cancer prior to splenectomy in some of the studies [15]. Spleen preservation procedures, including non-surgical management and the arterial embolization of a laceration, have, to a large extent, replaced total splenectomy. Currently, 90% of splenic tears are treated medically. Tonsillectomy and adenoidectomy In humans, the pharyngeal tonsil and the palatine tonsils represent the main mass of the Waldeyer’s ring. In these tissues, the intraepithelial and subepithelial lymphoid cells give rise to both local and systemic immunological reactions. However, it seems that in children a Th1 cellular response is predominant in the pharyngeal tonsils, whereas a Th2 humoral immune reaction prevails in the adenoid [18]. Total tonsillectomy is performed less frequently than in the past in most medical centers. The indications for this procedure are limited to medically resistant tonsillitis or suspected malignancy. In the majority of these cases, the sublingual tonsil is not damaged. It appears that the incidence of or opharyngeal carcinoma, mainly the HIV-related type, is increasing worldwide. In a large study from Denmark, no association between tonsillectomy and oropharyngeal carcinoma or other malignant tumors has been found. However, tonsillectomy decreased the risk of tonsil carcinoma to a significant degree [19]. In Taiwan, in contrast, a national study has found a significantly increased risk of developing cancer after a tonsillectomy at a rate of 4.28 per 1,000 person-years compared with 2.9 per 1,000 person-years in non-tonsillectomized controls. No site-specific association with any particular type of cancer has been found, except for a nearly significant link with breast cancer at 3 years or more after the tonsillectomy [20]. A cohort of 215 patients was identified who had developed gallstones and had undergone cholecystectomy or tonsillectomy. An association between gallstones, the surgical procedures and pancreatic cancer was apparent. Although having gallstones and undergoing a cholecystectomy significantly increases the risk of pancreatic cancer, a tonsillectomy reduces the tendency to develop this cancer [21]. Finding an incidental cancer during a routine tonsillectomy occurs very rarely (11 cases in 72,322 procedures [0.015%]). This finding does not justify performing a routine tonsillectomy on clinically benign tonsils [22]. The associations among tonsillitis, tonsillectomy and Hodgkin lymphoma was examined in all Danish residents between 1977 and 2001. Hodgkin lymphoma was diagnosed in 2,988 residents. Of these, 58 residents had undergone tonsillectomy after tonsillitis, and 14 suffered from tonsillitis only. These results suggest that tonsillitis is a risk factor for Hodgkin lymphoma, irrespective of the age of the patient [23]. The reports linking a greater incidence of Hodgkin lymphoma after tonsillectomy have shown some inconsistencies. The age at tonsillectomy has especially varied. Irrespective of the tonsil immune functions and their alterations during growth, a marked risk of Hodgkin lymphoma has been found in patients who had undergone tonsillectomy before age twelve. However, this risk is substantially decreased if the resection was performed at an older age [24]. However, when a tonsillectomy and an adenoidectomy were performed an older age the risk of adult lymphocytic leukemia, but not of myeloid leukemia, is markedly augmented. The cutoff point for performing these surgeries was at 10 years of age [25]. An immunological in vestigation was conducted in 80 children who had undergone tonsillectomy for chronic tonsillitis. In this study, no change in serum immunoglobulins was found after surgery. The subjects’ pre-operative peripheral lymphocyte count was higher than that of the controls, but was restored to near normal after surgery. Improved cell-mediated skin tests with PPD and Candida were observed after tonsillectomy.The immune response at 2448 hours before and at 4-6 weeks after an adenotonsillectomy has been analyzed in children with adenoid hypertrophy and chronic tonsillitis. Increased levels of CD19+ and CD23+ B-lymphocytes were found before resection. After ablation, B-lymphocyte activation was normalized, CD8+ T-lymphocyte levels were increased, and mild reductions in IgG, IgA and IgM were noted. A compensatory reaction had occurred but no immune deficiency was found.