Cody A. Koch

Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment.

OBJECTIVE To define associated clinical conditions, pathology, natural history, and treatment outcome of nonhepatosplenic extramedullary hematopoiesis (NHS-EMH). PATIENTS AND METHODS We retrospectively reviewed the medical charts of all patients identified as having NHS-EMH from 1975 to 2002. Diagnosis was made by tissue biopsy, fine-needle aspiration biopsy, or radionuclide bone marrow scanning. RESULTS We identified 27 patients with antemortem diagnosis of NHS-EMH. The most common associated condition and disease site were myelofibrosis with myeloid metaplasia (MMM) (in 18 patients [67%]) and the vertebral column (in 7 patients [26%]; all involving the thoracic region), respectively. At the time of diagnosis of NHS-EMH, concurrent splenic EMH (in 22 patients [82%]; 15 [56%] had undergone splenectomy) and red blood cell transfusion dependency (in 12 patients [44%]) were prevalent. Of the 27 patients, 9 (33%) required no specific therapy. Specific therapy was radiation (in 7 patients with a 71% response rate) and surgical excision (in 6 patients with a 67% response). Treatment-associated complications were limited to surgery. Radiation therapy was not used in the non-MMM group, but low-dose radiation therapy was used in the MMM group for paraspinal or intraspinal EMH (median dose, 1 Gy; range, 1-10 Gy), pleural or pulmonary disease (median dose, 1.25 Gy; range, 1.00-1.50 Gy), and abdominal or pelvic disease (median dose, 2.02 Gy; range, 150-4.50 Gy). Median survival after the diagnosis of NHS-EMH was 13 months in the MMM group and 21 months in the non-MMM group. CONCLUSIONS This retrospective study suggests that NHS-EMH is rare, is often associated with MMM, and preferentially affects the thoracic spinal region. Asymptomatic disease may require no specific treatment, whereas symptomatic disease is best managed with low-dose radiation therapy.

Accommodation: Preventing Injury in Transplantation and Disease

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as “accommodation.” In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.

Immunosuppression by Embryonic Stem Cells

Embryonic stem cells or their progeny inevitably differ genetically from those who might receive the cells as transplants. We tested the barriers to engraftment of embryonic stem cells and the mechanisms that determine those barriers. Using formation of teratomas as a measure of engraftment, we found that semiallogeneic and fully allogeneic embryonic stem cells engraft successfully in mice, provided a sufficient number of cells are delivered. Successfully engrafted cells did not generate immunological memory; unsuccessfully engrafted cells did. Embryonic stem cells reversibly, and in a dose‐dependent manner, inhibited T‐cell proliferation to various stimuli and the maturation of antigen‐presenting cells induced by lipopolysaccharide. Inhibition of both was owed at least in part to production of transforming growth factor‐β by the embryonic stem cells. Thus, murine embryonic stem cells exert “immunosuppression” locally, enabling engraftment across allogeneic barriers.

Natural mechanisms for evading graft rejection: the fetus as an allograft

Abstract.Most primitive multicellular animals mount allogeneic immune responses to protect themselves from invasion by foreign organisms. The reproductive success of eutherian mammals, in which the maternal immune system is in direct contact with the semi-allogeneic fetus, depends on the ability to control allogeneic immune responses. Multiple, overlapping mechanisms exist to prevent maternal allogeneic immune responses towards the fetus while maintaining the capacity to mount a defense against infectious organisms. The formation of an anatomical barrier between mother and fetus, lack of maternal immune responsiveness, and a lack of expression of allogeneic molecules by the fetus have been proposed as mechanisms to account for the lack of fetal rejection during pregnancy. These mechanisms have helped us begin to understand how rejection of the fetus is avoided; however, these mechanisms do not completely explain how the fetus evades the maternal immune system. Site-specific suppression, in which maternal immune responses are controlled locally at the maternal- fetal interface, plays a fundamental role in controlling maternal allogeneic immune responses. Stem cells, both adult and embryonic, might use mechanisms similar to those of the fetus to avoid rejection. Future discoveries in the field of reproductive immunology will help us understand not only immune regulation during pregnancy, but also how immune responses towards organ and cellular transplants might be controlled.

Complement-Dependent Control of Teratoma Formation by Embryonic Stem Cells

The fetus has pluripotent stem cells that when transferred to mature individuals can generate tumors. However, for reasons yet unknown, tumors form rarely in the fetus and/or the mother during normal gestation. We questioned whether the complement system might protect against tumor formation by pluripotent stem cells. Murine embryonic stem cells were notably more susceptible than cardiomyocytes differentiated from those cells to lysis by complement in heterologous and homologous sera. Treatment of embryonic stem cells with heterologous serum averted tumor formation after residual cells were transplanted into mice. Confirming the importance of homologous complement in preventing formation of tumors, untreated embryonic stem cells formed tumors more quickly in C3-deficient than in wild-type mice. Susceptibility of embryonic stem cells to complement required an intact alternative pathway and was owed at least in part to a relative deficiency of sialic acid on cell surfaces compared with differentiated cells. Susceptibility to complement and resistance to tumors was inversely related to the number of cells transferred. These findings show that formation of tumors from embryonic stem cells is controlled in part by the alternative pathway of complement and suggest that susceptibility to complement might represent a general property of pluripotent stem cells that can be exploited to prevent tumor formation.

Intrinsic resistance of hepatocytes to complement-mediated injury

When activated on or in the vicinity of cells, complement usually causes loss of function and sometimes cell death. Yet the liver, which produces large amounts of complement proteins, clears activators of complement and activated complexes from portal blood without obvious injury or impaired function. We asked whether and to what extent hepatocytes resist injury and loss of function mediated by exposure to complement. Using cells isolated from porcine livers as a model system, we found that, in contrast to endothelial cells, hepatocytes profoundly resist complement-mediated lysis and exhibit normal synthetic and conjugative functions when complement is activated on their surface. The resistance of hepatocytes to complement-mediated injury was not a function of cell surface control of the complement cascade but rather an intrinsic resistance of the cells dependent on the PI3K/Akt pathway. The resistance of hepatocytes to complement might be exploited in developing approaches to the treatment of hepatic failure or more broadly to the treatment of complement-mediated disease.

Transoral robotic surgery for supraglottic squamous cell carcinoma

PURPOSE We present our experience with the use of transoral robotic surgery (TORS) for treatment of supraglottic squamous cell carcinoma. MATERIALS AND METHODS We studied all patients who underwent TORS for supraglottic squamous cell carcinoma, with or without adjuvant therapy, from March 2007 through June 2009, who had a minimum of 2 years of follow-up. Primary functional outcomes included dysphonia, tracheostomy dependence, and gastrostomy tube dependence. Disease control and survival were estimated with the Kaplan-Meier method. RESULTS Of 9 patients in the study group, 7 (78%) had advanced-stage disease. All 9 patients had negative margins after TORS, with no perioperative complications. Regional recurrence and local recurrence developed in 1 patient each. One patient died of disease. At last follow-up, 7 patients (78%) were tracheostomy free, and 7 (78%) were gastrostomy tube free. CONCLUSIONS Transoral robotic surgery is a promising modality for resection of supraglottic squamous cell carcinoma. Transoral robotic surgery achieved functional laryngeal preservation in most patients with no complications.

Inferior vena cava filters in trauma patients: efficacy, morbidity, and retrievability.

BACKGROUND Thromboembolic events are potentially devastating sources of morbidity in trauma patients. With increasing experience and the introduction of retrievable devices, there has been a renewed interest in inferior vena cava (IVC) filters in trauma patients. METHODS The records for consecutive trauma patients undergoing IVC filter placement during the years 2001 to 2005 were reviewed, and clinical, demographic, and procedural data were evaluated for associations with thromboembolic events and device complications. RESULTS During the study years, 226 trauma patients had IVC filters inserted, and 140 of these patients (62%) had retrievable IVC filters placed. Six patients (3%) had a pulmonary embolism with the filter in place, and two patients (1%) had a pulmonary embolism after filter removal. The most common complication was thrombosis in 27 patients (12%), with clinically significant thrombus occurring in 15 patients (7%). There was no association between the type of filter (permanent or retrievable) or the brand of retrievable filter and thrombosis. Specific risk factors for thrombosis could not be identified. Retrievable filters were successfully removed in 61% of patients with retrievable filters. Technical success rate was 97% in those patients who underwent attempted removal. Removal was completed at a median of 21 days (range, 2-292 days). CONCLUSIONS Retrievable IVC filters in trauma patients are safe, but complications do occur with thrombosis being the most common. Retrieval has a high technical success rate when attempted. However, a significant number of trauma patients are lost to follow-up and this may impact the utilization of retrievable filters in this patient population.

Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test

Background: Cephalosporin administration in patients with a history of penicillin allergy is controversial. Studies looking at the safety of cephalosporin in patients with a history of penicillin allergy lacked a control group, had a small number of patients, and/or lacked confirmation of penicillin allergy by penicillin skin testing. The purpose of this study was to determine whether patients with penicillin allergy were at increased risk of adverse drug reactions when administered cephalosporin. Methods: A cohort study of patients with a history of penicillin allergy and a positive or negative penicillin skin test when administered cephalosporin was conducted. Charts were reviewed for adverse drug reactions to cephalosporin after penicillin skin testing. Results: Eighty-five patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin. Five (6%) of 85 cases had an adverse drug reaction to cephalosporin as compared to 5 (0.7%) of 726 of the referent population (p = 0.0019). The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2 (2%) of 85 compared to 1 (0.1%) of 726 amongst the referent population (p = 0.0304). Conclusion: A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. We recommend penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.

Oral cavity and oropharynx squamous cell carcinoma with metastasis to the parotid lymph nodes

To increase awareness of the potential of oral and oropharyngeal squamous cell carcinoma (SCC) to metastasize to the parotid region. We retrospectively reviewed patients who had undergone parotidectomy for metastatic oral or oropharyngeal SCC at a single tertiary care facility from January 1988 to January 2004. Exclusion criteria were a history of cutaneous SCC of head and neck or extension of primary tumor into the parotid gland. Twelve patients met study criteria. Parotid metastasis represented the initial disease manifestation in 4 cases. In 1 case, parotid metastasis presented synchronously with the primary tumor. Parotid metastasis represented recurrent disease in the other 7 cases. Primary subsites included tongue base (n=4), tonsil (n=3), lateral pharyngeal wall (n=2), oral floor (n=1), maxillary alveolus (n=1), and retromolar trigone (n=1). Pathologic findings showed grade 3 or 4 SCC in all patients. Parotid metastasis was located in the inferior parotid nodes in 7 cases; multiple superficial nodes, 3 cases; and both deep and superficial nodes, 2 cases. Oral and oropharyngeal SCC can metastasize to the intraparotid lymph nodes. The inferior parotid nodes are most commonly involved, and patients generally have substantial associated cervical metastases. When treating patients who have oral or oropharyngeal cancer with substantial cervical metastasis, physicians should consider removing the inferior parotid lymph nodes. We recommend that when intraparotid lymph node metastasis is detected, total parotidectomy and multidisciplinary adjuvant therapy should be conducted.