Long-term follow-up after meshectomy with acellular human dermis repair for postherniorrhaphy inguinodynia.

HYPOTHESIS: Direct inguinal hernia repair with acellular human dermis (AHD) may offer greater symptom improvement and lower risk of hernia recurrence than anatomical repair without mesh (AWM) after mesh removal (with or without neurectomy) for postherniorrhaphy inguinodynia. DESIGN: Retrospective cohort study with long-term follow-up. SETTING: Tertiary referral center for mesh inguinodynia. PATIENTS: Patients undergoing meshectomy (with or without neurectomy) for postherniorrhaphy inguinodynia were identified. Medical records were reviewed, and patients were contacted to evaluate outcomes. Patients whose postmeshectomy hernias were repaired using AHD vs AWM were compared. MAIN OUTCOME MEASURES: Patient satisfaction and recurrence. RESULTS: Sixty-seven patients (35 in the AHD group and 32 in the AWM group) completed the follow-up. Patient demographics, duration and severity of symptoms, and time to meshectomy were similar between groups. The mean length of follow-up was 31.9 months for the AHD group and 80.2 months for the AWM group (P < .001). Fewer neurectomies were performed in the AHD group than in the AWM group (43% [15 of 35] vs 72% [23 of 32], P = .03). Eighty-three percent (29 of 35) of patients in the AHD group reported good or excellent groin pain improvement compared with 72% (23 of 32) of patients in the AWM group (P = .38). Eighty-three percent (29 of 35) of patients in the AHD group were satisfied with results compared with 81% (26 of 32) of patients in the AWM group (P = >.99). The AHD vs AWM procedures were associated with similar recovery, time to hernia recurrence, complication rates (11% [4 of 35] vs 3% [1 of 32], P = .36), and hernia recurrence rates (9% [3 of 35] vs 12% [4 of 32], P = .80). Predictors of patient dissatisfaction with meshectomy included patient smoking (odds ratio, 9.1; P = .01) and filing of workers' compensation claims (odds ratio, 12.8; P = .02). CONCLUSIONS: Meshectomy (with or without neurectomy) for postherniorrhaphy inguinodynia leads to significant symptom improvement and patient satisfaction, with acceptable morbidity and recurrence rates. The use of AHD vs AWM does not improve iatrogenic hernia recurrence.

Differential internalization of hu14.18-IL2 immunocytokine by NK and tumor cell: impact on conjugation, cytotoxicity, and targeting.

The hu14.18-IL2 (EMD 273063) IC, consisting of a GD(2)-specific mAb genetically engineered to two molecules of IL-2, is in clinical trials for treatment of GD(2)-expressing tumors. Anti-tumor activity of IC in vivo and in vitro involves NK cells. We studied the kinetics of retention of IC on the surface of human CD25(+)CD16(-) NK cell lines (NKL and RL12) and GD(2)(+) M21 melanoma after IC binding to the cells via IL-2R and GD(2), respectively. For NK cells, ∼ 50% of IC was internalized by 3 h and ∼ 90% by 24 h of cell culture. The decrease of surface IC levels on NK cells correlated with the loss of their ability to bind to tumor cells and mediate antibody-dependent cellular cytotoxicity in vitro. Unlike NK cells, M21 cells retained ∼ 70% of IC on the surface following 24 h of culture and maintained the ability to become conjugated and lysed by NK cells. When NKL cells were injected into M21-bearing SCID mice, IT delivery of IC augmented NK cell migration into the tumor. These studies demonstrate that once IC binds to the tumor, it is present on the tumor surface for a prolonged time, inducing the recruitment of NK cells to the tumor site, followed by tumor cell killing.

Body mass index does not affect postoperative morbidity and oncologic outcomes of total mesorectal excision for rectal adenocarcinoma.

INTRODUCTION: Obesity adds to the technical difficulty of colorectal surgery and is a risk factor for postoperative complications. We hypothesized that obese patients have increased morbidity and poor oncologic outcomes after proctectomy for rectal adenocarcinoma. METHODS: Adult patients undergoing total mesorectal excision (TME) for rectal adenocarcinoma at a tertiary referral center were retrospectively identified from a prospectively maintained database. Operative characteristics, postoperative complication rates, and oncologic outcomes were compared in patients with BMI > or = 30 kg/m(2) and BMI < 30 kg/m(2). RESULTS: Between 1997 and 2009, 254 patients underwent proctectomy for rectal adenocarcinoma, of whom 27% were obese. There were no significant differences in demographics, comorbidities or preoperative oncologic characteristics between obese and nonobese groups. Patients with BMI > or = 30 kg/m(2) had longer operative times (p = 0.04) and higher intraoperative blood loss (p < 0.001) but comparable postoperative complication rates (p = 0.80), number of lymph nodes retrieved (p = 0.57), margin-negative resections (p = 0.44), and disease-free survival (p = 0.11). Obese patients had longer overall survival (p = 0.05). Tumor stage was the only variable associated with disease-free (p < 0.001) and overall survival (p < 0.001). CONCLUSION: Despite increased technical difficulty of resection, obesity does not increase the risk of postoperative morbidity or adversely affect oncologic outcomes after total mesorectal excision of rectal adenocarcinoma.

Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma.

PURPOSE: Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence. EXPERIMENTAL DESIGN: In this preclinical study, we sought to enhance the antitumor effect of RFA by combining it with huKS-IL2 immunocytokine [tumor-specific monoclonal antibody fused to interleukin-2 (IL2)] in mice bearing CT26-KS colon adenocarcinoma. Mice were treated with RFA, huKS-IL2 via intratumoral injection, or combination therapy. RESULTS: Treatment of mice bearing s.c. tumors with RFA and huKS-IL2 resulted in significantly greater tumor growth suppression and enhanced survival compared with mice treated with RFA or huKS-IL2 alone. When subtherapeutic regimens of RFA or huKS-IL2 were used, tumors progressed in all treated mice. In contrast, the combination of RFA and immunocytokine resulted in complete tumor resolution in 50% of mice. Treatment of a tumor with RFA and intratumoral huKS-IL2 also showed antitumor effects against a distant untreated tumor. Tumor-free mice after treatment with RFA and huKS-IL2 showed immunologic memory based on their ability to reject subsequent challenges of CT26-KS and the more aggressive parental CT26 tumors. Flow cytometry analysis of tumor-reactive T cells from mice with complete tumor resolution showed that treatment with RFA and huKS-IL2 resulted in a greater proportion of cytokine-producing CD4 T cells and CD8 T cells compared with mice treated with RFA or huKS-IL2 alone. CONCLUSIONS: These results show that the addition of huKS-IL2 to RFA significantly enhances the antitumor response in this murine model, resulting in complete tumor resolution and induction of immunologic memory.

The development of antibody-IL-2 based immunotherapy with hu14.18-IL2 (EMD-273063) in melanoma and neuroblastoma.

Patients with high risk melanoma and neuroblastoma frequently experience recurrence despite surgical resection and appropriate adjuvant therapies. Immunotherapy with the immunocytokine hu14.18-IL2 (EMD-273063) was developed by means of fusion of two molecules of IL-2 to the monoclonal antibody, 14.18, that recognizes GD2, expressed on the earlier mentioned malignancies. This article will discuss the results of preclinical work using EMD-273063 therapy, including data suggesting that intratumoral therapy may have enhanced antitumor benefit compared with intravenous therapy. Initial clinical trials in adult melanoma and pediatric neuroblastoma have demonstrated acceptable toxicity profiles in dosing that induces immune activation. Preclinical and initial clinical data suggest greater efficacy in the setting of minimal residual disease; therefore, future clinical testing is planned to test the benefit of EMD-273063 in this setting.

Liver-directed treatment modalities for primary and secondary hepatic tumors.

Colorectal cancer liver metastases and hepatocellular carcinoma remain significant health problems in the United States and worldwide. Although surgical resection is often the treatment of choice, patient comorbidities or disease extent may preclude this option. Alternative approaches to primary and secondary hepatic malignancies have been developed, and their impact on disease control has been the subject of much recent study. These therapies can be administered alone but can also be effective when used in combination, or with other chemotherapeutic regimens. This article reviews the different techniques of liver-directed therapy and the available literature on short- and long-term outcomes.

Blunt thoracic aortic injury: open or stent graft repair?

BACKGROUND: Despite a lack of level I evidence, endovascular stent grafting is frequently used for the treatment of blunt thoracic aortic injury. The purpose of this study is to compare the outcomes between open and endovascular repair of traumatic rupture of the thoracic aorta. METHODS: This article is based on a single-institution review of all consecutive patients treated for blunt aortic injury at the University of Wisconsin Hospital and Clinics between October 1999 and May 2007. This study was reviewed and approved by the institutional review board. Patients were identified from our Level 1 trauma registry. Inclusion criteria for this study was based on computed tomographic or angiographic evidence of thoracic aortic injury distal to the left subclavian artery. Two groups were identified: patients who underwent open repair (OR) and, patients who underwent endovascular repair (ER). Patient demographics, mechanism of injury, Injury Severity Score, associated injuries, comorbid conditions, intraoperative findings, postoperative complications, and duration of hospital stay were analyzed. Data regarding these patients and their injuries were retrieved from our trauma registry as well as chart review and outpatient records. The outcomes from OR and ER were compared using the Fisher exact test. P values less than 0.05 were considered statistically significant. RESULTS: During the 8-year period, 26 consecutive patients were treated for blunt aortic injury (OR = 12 and ER = 14). There were 20 men, and the mean age was 36 years. There were no differences between the groups in the mechanism of injury, Injury Severity Score, or number of associated injuries on initial presentation. On an intent-to-treat basis, the endovascular therapy was technically successful 100% of the time. There was no procedure-related mortality. There was 1 patient, however, in the OR group with presumed recurrent laryngeal nerve palsy. There was no incident of treatment-related paraplegia in either group. The 1-year survival for OR and ER patients was 93% and 92%, respectively. At 1 year, 25% of patients in the OR group and 18% of patients in the ER group required reinterventions. Mean operating room time was 309 minutes for the ERs and 383 minutes for the patients who underwent OR. Intraoperative blood product administration was greater in the OR group (P = .055); there was no difference between the groups, however, in the total blood products administered for a given hospital stay. The mean duration of hospital stay was 13 days for the OR group and 13.9 days for the ER group. CONCLUSION: There were no significant differences with respect to morbidity or mortality between these 2 groups. These data suggest that ER is at least as safe as OR for blunt aortic injury.